2011 NATIONAL DROSOPHILA BOARD MEETING AGENDA Wednesday, March 7, 2012 Chicago 8 (Level 4), Sheraton Chicago Hotel & Towers Chicago, IL 3:00-6:00 PM

1. Introduction and Approval of the 2011 minutes (Liz Gavis) 2. GSA Expanding Opportunities (Adam Fagen) 3. President's Report (Liz Gavis) 4. Report of the 2012 Organizing Committee (Steve Crews) 5. 2013 Fly Meeting Organizers (Liz) 6. Report of the GSA Senior Director (Suzy Brown) 7. Treasurer’s Report (Pam Geyer) 8. Drosophila Board Election Report (Terry Orr-Weaver) 9. Image Award (David Bilder) 10. Sandler Lectureship Committee (Liz on behalf of Richard Mann) 11. Victoria Finnerty Undergraduate Travel Award (Helen Salz) 12. Asia-Pacific Drosophila Research Conference 2 (Kwang-Wook Choi) 13. Undergraduate Education Initiatives (Karen Hales) 14. Outreach and educating the public (Liz Gavis, Eric Baehrecke)

3:00-3:05 3:05-3:10 3:10-3:15 3:15-3:30 read only 3:30-3:40 3:40-3:55 3:55-4:00 read only 4:00-4:15 4:15-4:20 read only 4:20-4:25 4:25-4:30

BREAK 4:30-4:45 Community Resources and Projects 15. White Paper (Denise Montell) 16. Bloomington Stock Center (Kathy Matthews, Kevin Cook) 17. Kyoto Stock Center (Masa Itoh) 18. Indian Stock Center (VijayRaghavan) 19. Species Stock Center (Teri Markow) 20. Mexican Drosophila Species Stock Center (Juan Riesgo-Escovar) 21. Berkeley Drosophila Genome Project (Sue Celniker) 22. ModENCODE and ModENCODE II (Sue Celniker) 23. Drosophila Gene Disruption Project (Hugo Bellen) 24. Harvard Drosophila RNAi Screening Center (Stephanie Mohr) 25. Harvard Transgenic RNAi Project (Liz Perkins) 26. Vienna Transgenic RNAi Project (Lisa Meadows) 27. DIS (Jim Thompson) 28. FlyBase (Bill Gelbart) ADJOURN 6:00

1

4:45-6:00

1. Introduction (Liz Gavis) 2012 Board meeting attendees (Appendix 1) New members and guests attending the 2012 Board meeting: Adam Fagen (GSA Executive Director) Amy Bejsovec (2012 President-elect) Giovanni Bosco (Heartland Rep, beginning 2013) Laura Nilson (Canada Rep, beginning 2013) Lisa Meadows (Head of VDRC) Kwang-Wook Choi (for Henry Sun; 2013 APDRC Organizer) Masanobu Itoh (Director, Kyoto Stock Center) Toshiyuki Takano-Shimizu (Kyoto Stock Center) Brian Oliver (FlyBase Scientific Advisory Board)

3. President's report (Liz Gavis) **Phyllis Edelman (Manager, Communications & Public Relations for GSA) and Suzy Brown (GSA Senior Director) were instrumental in developing and coordinating the activites described below. During a discussion about concerns over the national funding situation for Drosophila research at the 2011 Board Meeting, we elaborated three challenges for the Drosophila community: 1) advocating for the NIH budget at the national level by getting Drosophila researchers on the FASEB board 2) educating other scientists and administrators within the NIH about the importance of this model organism 3) educating the general public about the contributions Drosophila research can and does make towards improving human health We are making some progress towards these goals with two initiatives at the Fly meeting: Science Advocacy Luncheon: The GSA has volunteered to sponsor a Science Advocacy luncheon, with the goal of updating Drosophila researchers on what’s going on in Washington and give us the tools to communicate with Members of Congress and other policymakers. Jennifer Zeitzer, PhD, Director of Legislative Affairs in the Office of Public Affairs at the Federation of American Societies for Experimental Biology will be the primary speaker. She will share her extensive knowledge of and experience with the “ins and outs” of the workings of our federal legislature system. 2

Unfortunately, only 10 people have signed up for the luncheon so we will need to do more promotion next year if we we think this is a valuable approach. Science writer: With the Board's approval (email vote taken last fall), we hired a professional science writer, Ricki Lewis (http://www.rickilewis.com/index.htm), to help disseminate the importance of Drosophila research to the public. Ricki, who was one of Thom Kaufman's first graduate students, is now a successful textbook and popular science author with extensive experience in communicating complex information about human genetics and genetic disease research to the press and public. She is very excited to be able to bring her expertise back to her former model organism. Her CV is included as Appendix 2. Press releases Phyllis and Ricki worked with the meeting organizers to identify plenary talks to highlight in two advance press releases. Ricki felt that it would be best to focus on topics with that are "hot" on the popular health agenda (stem cells, aging – always a favorite; metabolism – given diabetes and childhood obesity) or have broad popular science interest (butterfly migration) since these are what will interest the reporters. One release will therefore highlight stem cell research illustrated in four of the talks – DiNardo, Montell, Brill and Doe. The other will include Thummel (energy metabolism), Tower (aging), and Reppert (butterfly migration). Phyllis contacted all of the speakers, who were all more than willing to talk with Ricki. The press releases will be released through two science news distribution sites that GSA subscribes to and which are read by thousands of reporters: EurekAlert!, which falls under the auspices of AAAS and Newswise, which has a dedicated science distribution service. From these sources, many of the genetics/medical/health media – print, online, and broadcast – pick up information. Releases are sent to the distribution sites prior to the meeting but are “embargoed” until the meeting starts. A reporter can read the release and work on a story, but the story can’t be published or broadcast – online, in print, TV, radio etc. - until the embargo is lifted. We can't know in advance who will pick up the releases, but both distribution sources can offer some insight into usage, which Phyllis should be able to determine in about a month or so. In addition, Phyllis has a “Google Alerts” on for the Fly meeting, and will pick up some information that way. Phyllis has also identified Chicago-based media – including newspapers, TV and radio to whom she will “pitch” the news items. Ideally, we would like to convince the Chicago NPR affiliate – either TV or radio - to report on a story from the meeting. Finally, Phyllis has also been able to reach most of the Public Information Officers (PIO)s at the speakers' institutions, who are happy to help spread the word about what their faculty are doing. She will be sending the embargoed releases to the PIOs in case they want to work on their own release

3

The press releases will also be posted to the GSA website and FlyBase once the embargo is lifted. FlyNews: Denise Montell started FlyNews during her Presidency to make the Board's activities more visible to the Drosophila community and to publicize our resources and it continues to be a great success. I frequently receive very positive feedback from the community and I believe that it does indeed serve the purpose of opening communication between the Board and the people we serve. Suzy and the GSA have been extremely helpful in making sure FlyNews gets out.

4. Report of the 2012 Oganizing Committee (Steve Crews) Organizers: Celeste Berg, Stephen Crews, Erika Matunis, Kevin White The Organizing Committee was assembled in 2010 at the behest of Denise Montell, then President of Fly Board. We received valuable input at a luncheon meeting with the 2011 Organizing Committee and Suzy Brown at the San Diego conference. We began organizing this year’s meeting soon after. Most work was done by group emails, use of web-based worksheets accessible by the Committee, and an occasional phone call. The worksheets greatly facilitated communication and keeping track of our progress during selection of the plenary speakers, session chairs, and platform speakers. Overall, meeting organization progressed well. Most decisions were made by consensus, although specific tasks were relegated to individual members. Continual guidance and input from Suzy Brown was invaluable, and the entire GSA staff did an excellent job. In summary, the organizers worked well together, and we are confident that this will be a useful and memorable meeting. Interaction with the GSA Office Suzy Brown and the GSA team were a delight to work with. Suzy was kept in the loop on all of the deliberations of the Organizing Committee and provided rapid insights, answers, and assistance. The timeline that Suzy prepared was invaluable. The GSA staff designed the colorful Chicago design for the meeting and expertly assembled all of the written and digital information. Registration As before, only the schedule and lists of talks and posters are in the program book. The abstracts are available online. Pre-registration for the meeting is strong with 1481 people registered as of Feb. 28. For comparison, pre-registration numbers for recent years are as follows: 1414 (2011), 1516 (2010), 1383 (2009), 1343 (2008), 1345 (2007), 1241 (2006), 1451 (2005), and 1470 (2004). The meeting organizers, plenary speakers, and panelists for the Future Advances talks were provided free conference registration, as done in previous years. Everyone had to cover their lodging and travel costs. The Larry Sandler Award Winner receives

4

complementary airfare, registration, hotel accommodations, and GSA membership. Victoria Finnerty Memorial Fund travel grants were awarded to 6 undergraduate researchers, all of whom are presenting posters. Conference Sessions: Future Advances in Drosophila Research Panel The Organizing Committee gave a lot of thought to the subject for Wednesday’s night opening session. In recent years, the trend has been to have several speakers discuss a particular topic of historical interest. However, our Committee ultimately decided to eschew a historical topic, and instead we opted for a series of talks on “Future Advances in Drosophila Research”. We agreed on 4 speakers: Hugo Bellen, Trudy MacKay, Ross Cagan, and Dan Kiehart, and were delighted that all four agreed to participate. They will discuss (1) new technologies in Drosophila genetics (Bellen), (2) new technologies in microscopy and imaging (Kiehart), (3) modeling human disease and drug discovery in Drosophila (Cagan), and (4) the importance of quantitative genetics and genetic variation in Drosophila research (Mackay). Each speaker has ~15 minutes to outline these advances and the talks will be followed by a panel discussion. Plenary Speakers: During May 2011, the organizing committee assembled a list of potential plenary speakers. The criteria were scientific importance and novelty, breadth of topics, gender balance, foreign and domestic speakers, and a mixture of junior and senior faculty. In addition, we tried to select speakers that we have recently heard and are confident that they will give an excellent talk. No one was selected that had given a plenary talk within the last 10 years. We issued our 12 invitations in June and were delighted that all 12 accepted. These speakers are: Julie Brill, Stephen DiNardo, Chris Doe, Suzanne Eaton, Eileen Furlong, Thomas Kornberg, Manyuan Long, Denise Montell, Steven Reppert, Julie Simpson, Carl Thummel, and John Tower. We maintained custom by choosing a speaker whose research topic lies outside of Drosophila research. This researcher is Steven Reppert who will speak on his groundbreaking work on butterfly migration. One speaker we had originally invited, Erica Larschan, had to withdraw as she later learned that she would be giving birth around the time of the meeting. We wish her well and hope that future Organizing Committees consider inviting Erica to speak. Our Committee was delighted that John Tower agreed to substitute. Overall, we are thrilled with our line-up of plenary speakers. Platform and Poster Sessions: The platform and poster sessions were similar to the 2011 meeting. One change was to add a new session on Systems and Quantitative Biology. This idea was suggested to the committee by David Arnosti and Stas Shvartsman, and correspondingly we asked them to be the initial co-chairs. The committee felt that this addition was justified given increasing interest in systems biology, and the success of a workshop on this topic at the 2011 Drosophila Conference. Based on the last year’s abstract submission results, we decided to merge the Cell Cycle and Checkpoints and Cell Death sessions into a single session: Cell Cycle and Cell Death. Inadvertently, these sessions were listed

5

separately during abstract submission, so the Organizers merged them afterwards. This should be corrected for next year’ meeting. In addition, as also done last year, we divided the Cell Biology and Signal Transduction abstracts into Cell Biology and Signal Transduction and Cell Biology and Cytoskeleton sessions. Inadvertently, this separate session also did not show-up during abstract submission, and the Organizers partitioned these abstracts after submission. This should also be corrected for next year. We also changed the names of the two neurobiology sessions to: (1) Neural Development and (2) Neurophysiology and Behavior to clearly distinguish their different subjects. Due to the considerable amount of time required for poster judging at the Drosophila Meeting, it has become necessary to have co-chairs for all sessions. This was done last year, and we continued this practice this year. The Organizing Committee together devised a list of potential chairs for each session. We selected leaders in the field, while keeping gender balance and senior/junior faculty balance in mind. We also tried to recruit individuals who had not served recently. In most cases, we contacted a potential chair and when they accepted, we asked them to select a co-chair. We then invited that co-chair. We accepted their recommendation in most cases, but not all. For example, we tried to avoid having chairs from the same institution, even if they might work well together. Other times, we suggested potential co-chairs, and in all cases this arrangement was acceptable. Almost everyone contacted agreed to serve (names are in the table below). While the recruitment of co-chairs entails additional work by the Organizing Committee, one benefit is that it results in an additional 19 faculty each year that formally participate in the meeting. For junior faculty, this is likely to be a valuable experience. Abstract Submission. Abstracts were solicited in 19 topics and associated with keywords. We received 897 abstracts by the deadline. We also received 108 late abstracts for a total of 1005 abstracts. In addition, 9 abstracts were withdrawn. Totals in recent years were: 1066 (2011), 1046 (2010), 1020 (2009), 993 (2008), 897 (2007), 910 (2006), 1043 (2005), 972 (2004), 1016 (2003), 1003 (2002). There were 435 requests for platform talks for the 156 speaking slots. This allowed accommodation of 36% of the requests, which is the norm in recent years. Several abstracts were rejected as having no relevance to the meeting. The number of abstracts varied considerably among sessions (see table below) from 119 (Evolution & Quantitative Genetics) to 26 (RNA Biology). Both Cell Biology sessions together contained a total of 150 abstracts. Three sessions were selected to be double sessions because of their substantial number of abstracts that requested platform talks: Cell Biology and Signal Transduction (47), Evolution & Quantitative Genetics (61), and Regulation of Gene Expression (33). Drosophila Models of Humans Disease also had a substantial number of talk requests (35) and could have been chosen for a second session. Gene Expression was selected for the double session because of the very high number of abstracts that listed it as a second choice, indicating its popularity. For each session, co-chairs selected their speakers, placed them in order, and selected two alternates.

6

Platform Session Selection. In general, we left it up to the co-chairs to select the abstracts for presentation as talks. We sent the co-chairs a detailed letter describing our criteria for talk selection, which included scientific excellence, breadth, gender balance, and a mixture of graduate students, postdocs, junior faculty, and senior faculty. In a few cases, speakers were chosen from those listing a session as their second choice. Overall, we were pleased with the selections from the chairs. Nevertheless, we reviewed the proposed speakers and made a small number of changes. The reasons for our changes included: (1) too many talks from the same lab (usually spread-out over multiple sessions), (2) speakers cancelled or we were informed that they were unlikely to attend, (3) more than one talk in two different sessions by the same person, and (4) talks that seemed nearly identical to a previous year’s talk. Two larger labs (containing over 20 members) were awarded two talks, but this was the maximum number of talks per lab, so as to maintain diversity at the meeting. Poster Session. There are currently 849 posters (741 regular) and 108 (late). Co-Chairs

Cell biology and signal transduction Cell biology and cytoskeleton Cell cycle and cell death Cell division and growth control Chromatin and epigenetics Drosophila models of human diseases Evolution and quantitative genetics Gametogenesis and organogenesis Immunity and pathogenesis Neural development Neurophysiology and behavior Pattern formation Physiology and aging

Matt Gibson Kristi Wharton Sally HorneBadinovac Mark Peifer Nam-Sung Moon Kristin White Rachel SmithBolton Bill Sullivan Nicole Francis Leonie Ringrose Charles Nichols Udai Pandey Kelly Dyer Mohamed Noor Greg Beitel Lilach Gilboa Nancy Fossett Robert Schulz Greg Bashaw Pelin Volkan Dan Tracey Marta Zlatic Seth Blair Trudi Schüpbach Pankaj Kapahi Blanka Rogina

Secondary Topic

Primary topic Total # of Abstracts

# # Total # of Requesting Requesting abstracts Talk Poster

99

47

52

117

51

29

22

---

37

15

22

35

31

17

14

48

51

22

29

34

73

35

38

67

119

61

58

35

50

30

20

76

28

14

14

14

57

13

44

36

44

25

19

40

32

16

16

75

45

21

24

54

7

Regulation of gene expression RNA biology Stem cells Techniques and functional genomics Systems and quantitative biology Educational initiatives

Angela DePace Julia Zeitlinger Howard Lipshitz Jim Wilhelm Allison Bardin Todd Nystul Michelle Arbeitman Marc Halfon David Arnosti Stas Shvartsman

65

33

32

137

26

12

14

26

27

14

13

11

27

15

12

38

26

16

10

45

6

---

6

---

Poster Awards As in previous years, the award committee for posters consists of all of the platform session chairs that do the initial judging followed by the Meeting Organizing Committee that makes the final decision. The session chairs examine all posters in their session and select the best for each class (postdoc, graduate student, and undergraduate). PIs and technicians are not eligible for an award and their posters are not considered. The session chairs email their selections to the Organizing Committee by Friday evening of the meeting. The Organizing Committee will meet, examine the session winners, and then pick 1st, 2nd, 3rd place and honorable mention) for each class. Ribbons will be pinned on the wining posters so that attendees can examine the winning posters. The winners will be recognized during the plenary session on Sunday and their posters displayed outside the room. The GSA provides cash prizes and copies of Conversations in Genetics videos to the awardees. In addition, Howard Lipshitz has generously donated copies of his biography on Ed Lewis to the winners. Workshops There are a total of 8 workshops (see list below). Only the Organelles in the Drosophila Ovary workshop and Undergrad Researcher workshop were not present in last year’s program. We also note that last year’s Quantitative Biology of Cell Signaling and Pattern Formation workshop was transformed into a new platform session on Systems and Quantitative Biology. Overall, the workshops nicely complement the platform sessions, except that the presence of the apoptosis, autophagy, and other cell death mechanisms workshop meant the number of abstracts submitted for the cell death platform session was low. The Ecdysone workshop is held on Wednesday, as is tradition. Four other workshops run concurrently on Friday, including the Undergrad Researcher workshop, and the other three run concurrently on Saturday. Last year, the modENCODE workshop was held without a competing workshop, but this year it is being held as one of the three concurrent Saturday workshops. The Organizing Committee generally left the organization of the workshops to the workshop organizers. Workshop Schedule: Wednesday, March 7 12:00 NOON–6:00 PM Ecdysone Workshop Friday, March 9 1:45 PM–3:45 PM Organelles in the Drosophila Ovary Apoptosis, Autophagy and Other Cell Death Mechanisms 8

Chromosome Pairing and Dynamics in Meiotic and Somatic Cells Undergrad Researcher Workshop Saturday, March 10 6:45 PM–8:45 PM Everything You Ever Wanted to Know About Sex Drosophila Research and Pedagogy at Primarily Undergraduate Institutions (PUI) modENCODE Assistance to the 2013 Drosophila Conference Organizing Committee All of the worksheet templates and the tables listing previous speakers and session chairs will be made available to the 2013 Organizing Committee.

5. 2013 Meeting Organizers (Liz Gavis) The meeting organizers for the 2013 Drosophila Conference in Washington, DC are: Richard Mann, Columbia University Hannele Ruohola-Baker, University of Washington Kristin Scott, University of California, Berkeley David Stern, Janelia Farms

6. Report of the GSA Senior Director (Suzy Brown, CMP) 53rd ANNUAL DROSOPHILA RESEARCH CONFERENCE As you can see from the information in the treasurer’s report, while I budgeted for a loss of approximately $36,000, it looks like the loss won’t be quite that high. Registration: The total registration number for 2012 as of February 11 is 1,441. This number is even with last year at this time. The registration cut-off is February 29 so we may see a few more come in before we close out advanced registration. Registration income at this point is about $40,000 below the total budgeted registration income of $304,380. The number of individuals registering as GSA members is up 4% over last year. Currently 72% of the people attending the conference are GSA members. Hotel Rates and Pick-up: The average sleeping room rate is $219 which is an increase of approximately 30% from last year although about even with the previous year. The “official” cut-off date has passed, however, the hotel has agreed to extend our cut-off since we are very close to contracted pick up. I believe that with the close proximity of other hotels, we have people going around the block to less expensive venues. Since many of our concessions are tied to our pickup in the hotel, we are hopeful that we are able to meet our contractual obligations. As of right now I am optimistic that this will happen. 9

Exhibitors/Sponsorship/Advertising: We sold seventeen booths this year which is down three from last year. Web advertising and print ads are up slightly. Other GSA Conferences have had great success with organizers and other attendees approaching their vendors for sponsorship dollars and that is probably an additional approach that should be implemented next year. Other Items: I would like to get the Board’s feedback on the possibility of capturing the slides and audio from the platform and plenary sessions in future years. We would, of course, ask for permission from the presenters but I think this is a great way to market the meeting and build attendance. I recently participated in a conference where data was presented showing the increase in attendance based on providing educational information from prior conferences. If this is something that the Board would be in agreement with, we will start capturing this information in 2013 and make it available on GSA’s website. FUTURE CONFERENCES Dates and rates have been confirmed through 2016 and the Town & Country is holding space for us for 2017. Detailed below is the schedule for the next five years: 2013 – 54th Annual Drosophila Conference: April 3-7, Marriott Wardman Park Hotel. $235 2014 – 55th Annual Drosophila Conference: March 30-April 3, The Town and Country Resort Hotel, San Diego. $192/$202/$232. 2015 – 56th Annual Drosophila Conference: March 4-8, Sheraton Chicago Hotel and Towers. $219/$239. 2016 – 57th Annual Drosophila Conference: March 2-6, Philadelphia Marriott. $179 2017 – 58th Annual Drosophila Conference: Dates TBD – San Diego, CA The next open year is 2018 which would normally be a Chicago rotation but I would like to suggest that we look at a few other locations as well including Orlando, Indianapolis and Las Vegas. I know that some of these sound like unconventional locations but Orlando and Las Vegas have proven to be excellent draws for meetings because of the “lift” (air access) into the cities (both nationally and internationally) and their affordability. Indianapolis, while not the draw because of the city itself, is a very affordable city with great lift as well. If the Board thinks we could consider these options, I can add a question to the conference survey to see how the attendees would feel about those three locations. If the response is positive, I can present you with additional information in the coming month.

10

Registrations - 2012

Number

Amount

Faculty/Lab Tech Members

415

$87,350

Faculty/Lab Tech NonMembers

112

$42,765

Postdoc Members

201

$38,215

Postdoc Nonmembers

81

$24,045

Grad Student Members

325

$30,510

Grad Student Nonmembers

172

$27,970

Undergrad Members

94

$3,340

Undergrad Nonmembers

24

$2,640

Complimentary

17

0

1,441

$256,835

Early/Regular

11

United States Canada United Kingdom Germany Japan France Taiwan Spain Israel Mexico South Korea Togo China Sweden Switzerland Italy India Singapore Austria Belgium Chile Australia Brazil Czech Republic Portugal Russian Federation Norway Slovakia

Registrants by Country 1121 63 32 27 24 23 22 18 16 10 10 10 8 8 8 6 5 5 4 4 4 3 2 2 2 2 1 1

Total number of registrants: 1441 28 countries

12

7. Treasurer’s report (Pam Geyer) Drosophila Main Fund: The main fund is $325,830. This fund continues to grow and far exceeds the minimum required by the GSA ($150,000). Based on pre-registration numbers, Suzy Brown (GSA) projects we will lose $22,600 at the 2012 Chicago meeting. Over the last ten years, we have increased our reserves $283,360, and have only lost money three of these years [2003, Chicago $22,993; 2008 San Diego, $5,410; and 2009, Chicago $47,935; Total $76,338]. In 2008-2009, the losses included providing box lunches for a networking luncheon for all participants. Although sponsorship is lower this year than in previous years, it is consistent with the 2009 numbers for Chicago ($32,300). Historically, sponsorship income comprises ~10% of the income generated, with the bulk of the remaining monies generated by registration fees. The amount of projected loss ($26,600) can be easily covered by our main fund, which will leave $299,230 in our main fund. Even with this projected loss, we still will have $149,230 more than the minimum needed. Further, the upcoming venues for the 2013/ 2014 Drosophila conferences are Washington, DC and San Diego, CA, which historically have generated income. Sandler Lecture Fund: The lecture fund is $30,480. This fund generated a net income of $555, which offset the travel cost of $430. This year travel cost was $442, which is in line with our income. At the present time, the income and expenses are aligned. Recommendations: Registration fees should not be raised. Further, there is excess money in the main fund that should be used for community enrichment. Proposals for use of our resources: 1. Reduce registration for the 2013 meeting by $15 per person (based on the net income/ number of attendees at the past 2010 Washington DC meeting). 2. Provide travel awards for trainees: Recommend at least six $1,000 awards per year (Total cost $6,000). 3. Continue to hire professional writer to increase visibility of basic science discoveries pertinent to advancing human health: funding for Drosophila conference and GSA Model Organisms to Human Biology. Estimated cost $10,000 per year. 4. Add funds to the Larry Sandler Award to secure this award. Summary: proposal includes recurring costs of ~$16,000 per year. Discussion points (Liz): Should we establish and Executive subcommittee to oversee management of our funds? Should we move the Larry Sandler Fund investments (Appendix 3) into the same portfolio as our main investments?

13

Table 1: Summary of expenses: 2009-2012 Chicago* 2009 Actual

Wash., DC 2010 Actual

San Diego 2011 Actual

Chicago 2012 Budget

Chicago 2012 Estimate

$307,237

$304,380

305,000

REVENUE Registration Fees

$294,266

$306,393

Sponsorships/Ads Exhibit Fees

$ $

6,100 25,650

$3,000 $31,750

2,500 35,000

5,500 35,000

2,000 30,300

Miscellaneous (t-shirts, etc.)

$

4,170

$3,815

4,020

4,100

5,500

TOTAL REVENUE

$ 330,186

$344,958

$348,757

$348,980

342,800

$ 79,502 $ 17,140 $ 148,370 $ 19,004 $ 791 $ 3,758 $ 86,901

$66,747 $14,662 $110,848 $20,701 $1,452 $2,835 $54,458

$59,631 10,297 104,145 17,869 1,183 4,321 54,728

$ $ $ $

$4,371 0 $9,422 $3,773 $28,606

3,224 343 9,070 1,615 17,860

$80,850 14,700 131,500 22,000 3,500 5,500 71,000 10,000 4,700 6,900 10,000 1,000 24,000 $385,650

75,000 12,000 131,500 22,000 3,500 5,500 71,000 0 4,000 6,900 10,000 3,000 21,000 4,000 365,400

EXPENSE Salary, Payroll Tax and Benefit Printing/Mailing/Promotion Receptions and Catered Events Posters/Exhibits Supplies/Duplicating/Signs Hotel and Travel Audio Visual Services Awards Other Contracted Services Telephone/Internet/Fax Credit Card Fees Miscellaneous (t-shirts, etc.) Overhead Professional writer

NET GAIN (LOSS)

3,604 1,447 7,672 9,929

$ 378,118

$317,876

$284,286

$ (47,932)

$27,082

$64,471

*Luncheon added without registration price increase.

14

$(36,670) $(26,600)

B. MEETING ATTENDANCE Pre-registration 2012 (Chicago): Total registration 2012 (est):

1,367 $234,928 1,521 $305,000

Pre-registration 2011 (San Diego, CA): Total registration 2011:

1,328 $243,004 1,541 $307,237

Pre-registration 2010 (Washington, DC): Total registration 2010:

1,529 $261,246 1,668 $306,393

Pre-registration 2009 (Chicago): Total registration 2009:

1,383 $256,800 1,506 $294,266

Pre-registration 2008 (San Diego) : Total registration 2008:

1,343 $214,856 1,447 $281,093

Pre-registration 2007 (Philadelphia): Total registration 2007:

1,345 $234,000 1,507 $288,067

Pre-registration 2006 (Houston): Total registration 2006:

1,241 $222,165 1,402 $274,350

Pre-registration 2005 (San Diego): Total registration 2005:

1,451 $264,440 1,515 $297,750

Pre-registration 2004 (Wash DC): Total registration 2004:

1,470 $266,110 1,617 $313,645

Pre-registration 2003 (Chicago): Total registration 2003:

1,488 $256,130 1,603 $283,270

Pre-registration 2002 (San Diego): Total registration 2002:

1,219 $211,000 1,552 $290,170

Pre-registration 2001 (Wash DC): Total registration 2001:

1,372 $240,240 1,627 $297,915

15

C. ACCOUNT BALANCES C.1. Drosophila Main Fund Table 2: Summary of income and attendance since 1993 Meeting Year 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

Location San Diego Chicago Atlanta San Diego Chicago Wash DC Seattle Pittsburgh Wash DC San Diego Chicago Wash DC San Diego Houston Philadelphia San Diego Chicago Washington, DC San Diego

Net Income $17,105 2,800 8,417 15,035 31,663 21,522 (6,053) (56,060) 71,656 60,661 (22,993) 23,026 89,943 6,196 16,663 (5,410) (47,935) 27,082

Fund Balance* $ 25,146 27,946 36,363 51,398 83,061 104,583 98,530 42,470 114,126 174,787 151,794 174,820 264,763 270,959 287,622 282,212 234,277 261,359

64,471

325,830

# Meeting Attendees 1,165 1,222 1,103 1,423 1,382 1,378 1,366 1,183 1,627 1,552 1,603 1,617 1,515 1,402 1,507 1,447 1.506 1,668 1,541

* The GSA Board (Sept. 2003 meeting) established a required ~$150,000 minimum reserve fund (one-half of meeting expenses). No cap figure stated

16

C. 2. Sandler Lecture Fund Table 3: Summary of Sandler fund expenses

Year

1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

Investment Gain

1076 1963 2187 -859 1198 947 555

Travel expenses

1,208 469 501 441 768 1,482 420

Supplies/ Mailing expenses

37 15 15 20

Net Income

Balance

1417 (451) 1,595 1,142 1,119 1,385 877 257 (234) (846) (2,431) 432 (169) 1,479 1,671 (1,320) 430 (555) 135

25,964 25,513 27,108 28,250 29,369 30,754 31,631 31,888 31,654 30,808 28,377 28,809 28,640 30,119 31,790 30,470 30,900 30,345 30,480

8. Drosophila Board Election Report (Terry Orr-Weaver)   I. Committee, selection process The Elections Committee consisted of Terry Orr-Weaver (Chair), Debbie Andrew, Greg Beitel, Susan Parkhurst, and Laurel Raftery. Greg Beitel and Laurel Raftery will remain on the Elections Committee next year, but Debbie Andrew and Susan Parkhurst are rotating off. The next chair is Denise Montell. She will be reminded in the fall by Terry Orr-Weaver to organize the committee and select two new members for two-year terms. We collected suggestions from outgoing representatives and the committee members, and then ranked them based on previous involvement in the fly community or our perception of their ability to perform the job. The chair contacted the individuals selected by the committee to construct the final ballot (see below).

17

II. Voting process An email was sent to the Drosophila community on Nov. 14, 2011 from Flybase, and surveymonkey was used to quantify votes. The text of the email was: Dear Drosophila Researcher, The time has come again to cast your vote for new members of the National Drosophila Board of Directors. The Board plays an important role for the Drosophila research community, so please take a few seconds to learn about the Board on the link below and cast your vote. This year we are electing the President-elect, who will serve as President starting with the fly meeting in 2013. We are also electing representatives for the Mid-West, Heartland and Canada regions, who will serve 3-year terms starting with the fly meeting in 2013. Please participate in this election. It is your opportunity to choose the individuals who will help set priorities and garner support for community resources. Please remember you may vote for candidates in ALL categories even though you do not reside in the region represented by the candidates. Balloting will end December 20, 2011. http://www.surveymonkey.com/s/53JVGSK Thank you, Drosophila Board Election Committee Terry Orr-Weaver, Chair Debbie Andrew Greg Beitel Susan Parkhurst Laurel Raftery The surveymonkey ballot listed the following candidates: President (vote for one) Amy Bejsovec http://fds.duke.edu/db/aas/Biology/faculty/amy.bejsovec My laboratory explores the molecular mechanisms of pattern formation in developing embryos. We focus on the Wingless(Wg)/Wnt class of secreted growth factor: these molecules promote cell-cell communication leading to important cell fate decisions during the development of both vertebrate and invertebrate embryos. In addition, this highly conserved pathway is essential for maintaining stem cell populations and is associated with human cancers when inappropriately activated in adult tissues. Wg/Wnt molecules have proven difficult to work with biochemically because they associate tightly with cell membranes. Therefore, we exploit the powerful genetic and molecular techniques available in Drosophila to approach basic questions about Wg/Wnt signal

18

transduction. Current work in the lab includes analysis of genes discovered as suppressors or enhancers of wg mutant phenotypes, which may identify new control mechanisms for the pathway. We use cultured human cells to determine whether gene activities we have discovered and characterized in the fly embryo are relevant to the mammalian Wnt pathway as well. Henry Krause http://www.utoronto.ca/krause/ The initial focus of my lab was on homeodomain proteins and mechanisms of target gene recognition and regulation. More recently, the main interests have moved to two new areas. The first focuses on the process of mRNA localization within cells and how this affects protein and cellular functions. This began with a focus on the wingless gene and has expanded to a genome-wide analysis of all Drosophila mRNAs. The second project is a family-wide analysis of the functions, structures and cofactors of the nuclear receptor class of transcription factors. These projects began with Drosophila as the host organism, and have now expanded to zebrafish. Canada (vote for one) Tony Harris http://www.csb.utoronto.ca/faculty/harris-tony My lab uses confocal and time-lapse microscopy in combination with Drosophila genetics to study how epithelial cells are built and re-shaped to form the Drosophila embryo. Epithelia are the sheets of adherent cells that form boundaries between our body compartments. Each side of an epithelial sheet has distinct molecular properties. This epithelial polarity is critical for guiding embryo development and for directing adult functions (e.g. nutrient uptake in the gut), and its loss is associated with cancer. We are studying the polarity-organizing machinery operating in each epithelial cell. We focus on the PAR complex, made up of Bazooka (PAR-3), PAR-6 and aPKC, and are addressing how these proteins are positioned in the cell and how they affect downstream pathways (linked to cell adhesion and the cytoskeleton) to generate polarized cells and polarized cell shape changes. These processes are critical for establishing and maintaining epithelial polarity and for directing epithelial morphogenesis in the developing animal. Laura Nilson http://biology.mcgill.ca/faculty/nilson/ My research program investigates mechanisms of epithelial patterning and morphogenesis. We study how spatially and temporally localized positional cues generate a stereotyped pattern of cell fates within an epithelium. We are also investigating the molecular mechanisms that operate downstream of cell fate determination that influence the actin cytoskeleton and generate the changes in cell shape that orchestrate epithelial remodeling and migration.

19

Heartland (Vote for one) Giovanni Bosco http://www.bio5.org/biogate?cmd=fac&faculty_id=2384 The goal of my current research is to elucidate the molecular mechanisms through which dynamic changes in global chromosome structure and nuclear architecture impinge on functions such as chromosome segregation, gene expression, transsensitive effects and epigenetic gene silencing. My lab uses a variety of approaches including genetics, genomics, proteomics and microscopy. Specifically, we focus on the activities of condensin proteins and how these molecular machines alter the structure of chromosomes and thereby modulate cis- and trans- chromosomal interactions. Anthea Letsou http://www.genetics.utah.edu/hg-faculty/current-hg-faculty/100-human-genetics/hgfaculty/currentfaculty/168 In my lab, we employ genetic methods to identify, clone, and characterize genes required for dorsal closure, the morphogenetic process by which the embryonic lateral epidermal sheets spread dorsally to encase the developing embryo. Our work has contributed most significantly to our understanding of the JNK (Jun N-terminal kinase) and Dpp (Decapentaplegic) signaling cascades that function sequentially to direct dorsal closure. Most recently, we have focused our studies on Raw (a novel protein) and Mummy (a UDP-N-acetylglucosamine pyrophosphorylase), and their roles as novel JNK/AP-1 and Dpp signaling antagonists. Our studies are particularly significant as they allow us to find answers to unresolved questions of how the diverse JNK/AP-1 and Dpp pathway outputs translate into morphogenetic events (such as epithelial sheet movements) that are critical to the generation of tissues and organisms. Midwest (Vote for one) Seth Blair https://mywebspace.wisc.edu/ssblair/web/ We are currently pursuing two main avenues of research, both centered around development of the wing of the fruitfly, Drosophila melanogaster. First, we have been examining general aspects of pattern formation and cell lineage within the developing imaginal discs, the structures that give rise to the wing and notum. We have been concentrating upon the role of the lineage "compartments" and transcompartmental induction in specifying the basic axes of appendages, and the mechanisms by which the compartmental lineage restrictions are maintained. Second, we have been examining mutations that affect vein formation, as a means of uncovering novel players in cell signaling pathways. We are currently concentrating on a) signaling via the protocadherins Dachsous and Fat and their roles in proximodistal patterning, planar cell polarity and regulation of the Hippo growth pathway; b) the roles of the secreted BMPbinding proteins Crossveinless, Crossveinless 2, Crossveinless d and Short gastrulation

20

in the regulation of BMP signaling; c) the mechanisms by which the Wif-1/Shifted protein family of secreted proteins regulates Hedgehog and Wnt/Wingless signaling. Tom Hays http://www.gcd.umn.edu/html/faculty_pages/hays.html The Hays’ lab studies the regulatory mechanisms that drive intracellular transport. During mitosis, checkpoint proteins are stripped from kinetochores during the metaphase congression of chromosomes and prior to the onset of anaphase. We are studying how the motor protein, cytoplasmic dynein, contributes to mitosis, the transport of checkpoint proteins and genomic stability. In post-mitotic neurons, the extended morphology of axons and dendrites is especially dependent on polarized transport, and ideal for studying the regulation of transport. We are using genetic screens and live imaging to investigate transport mechanisms and Drosophila models of neurodegeneration. III. Results As of Dec. 19 we had 337 votes. Although this was comparable to the previous five years, we sent a reminder email to the community, reminding them to vote and extending the deadline to Jan. 6. Thom Kaufman quantified the total 466 votes on Jan. 9, with the following results: Amy Bejsovec for President-Elect, beginning March 2012 Laura Nilson for Canadian representative, beginning March 2013 Giovanni Bosco for Heartland representative, beginning March 2013 Seth Blair for Midwest representative, beginning March 2013 All of the candidates were notified of the results, and the President-Elect was asked to attend the 2012 board meeting. The regional representatives were invited to attend this year’s board meeting if they wanted, although their terms do not begin formally until the following year. One issue that arose that needs to be addressed next year is that it is important for each of the candidates to include a few sentences about their vision for the Drosophila board and past service. Several community members felt it was inadequate for the ballot to contain information solely about their research interests and lab websites.

21

9. Image Award (David Bilder) (Michelle Arbeitman, David Bilder, Ross Cagan, Anne Ephrussi, Bill Sullivan) This year's competition received 55 submissions, including 11 videos. The field this year was particularly deep and there were probably 20 entries worth finalist status. Nevertheless, the 2011winners in the still and video categories are: video: Saori Haigo, for her video illustrating global tissue rotation driving egg elongation still: KG Guruharsha, for his image depicting interactions among the Drosophila proteome This year's runners-up are: Daniel Vasiliauskas, for his image showing Rhodopsin exclusion in photoreceptors Pan Yufeng, for his video demonstrating the circuitry underlying mate recognition. Ross Cagan will make the Award presentation at the meeting. Changes: we will be increasing the eligible size of video uploads next year to accommodate demand, probably via a filesharing service.

10. Report on the 2012 Larry Sandler Memorial Award (Richard Mann) The 2012 Larry Sandler Memorial Award committee was chaired by Dr. Richard Mann (Columbia University) and included Dr. Ken Irvine (Rutgers), Dr. Michael Eisen (UC Berkeley), and Dr. Leslie Vosshall (Rockefeller University). Given the large number of nominations, it was helpful that the committee members were collectively expert in multiple different fields. We received an unprecedented 32 nominations (for comparison, last year’s committee received 7). Thanks to Suzy Brown’s efforts, better advertising and several reminders distributed to the community a few weeks before the deadline was a big reason for the increased number of nominations (more than half of the nominations were received in the last week). This should be standard procedure in future years, as the large number of nominations not only reflects well upon the field, it also more accurately represents the wide range of outstanding research being carried out using Drosophila. Extending the time frame for eligibility also helped to increase the number of nominations. The range of topics covered and high quality of the research represented in these nominations was truly impressive. One committee member wrote, “it was inspiring to read about the research of these outstanding young scientists and a testament to the bright future of Drosophila research”, while another put it more succinctly: “Jesus, that's a lot of good theses”.

22

Because of the large number, we went through two rounds of voting, first to pick the top 10 and then to rank those 10. Although it was not too difficult to pick the best 10, the committee agreed that any of these would make extremely worthy winners. In the end, however, when forced to rank these ten, there was remarkable consensus among the committee members. Below is the top three: Winner: Stephanie Turner Chen. Stephanie’s thesis advisor was Anandasankar Ray at UC Riverside. Her thesis title was, Odors that modify CO2 receptor activity in insects and their effect on innate CO2-mediated behavior”. She is currently a postdoc with David Julius, UCSF. Runners-up: Saori Haigo. Saori did her Ph.D. with David Bilder at UCSF. The title of her thesis was, Cellular and molecular mechanisms underlying tissue elongation of the developing egg in Drosophila melanogaster. Saori is currently a postdoc in Elly Tanaka’s lab at the Max Planck Institute. Daniel Matute. Daniel did his Ph.D. with Jerry Coyne at the University of Chicago where he worked on the mechanism of speciation in the melanogaster subgroup. He is currently a postdoc with Molly Przeworski at U. Chicago. It should be clear from just these three that the breadth of topics that the committee had to choose from was large and impressive. Richard Mann plans to present the award at this year’s meeting in Chicago. 2013 Sander Award Committee: Ken Irvine has agreed to chair the selection committee for the 2013 award. Discussion point: Only 4 women have received the award in the last 24 years – should we be worried about this disparity?

11. Victoria Finnerty Award for Undergraduate Travel (Helen Salz) (Karen Hales, Janis O'Donnell, Helen Salz) The new Victoria Finnerty Award, established by Scott Hawley, Janis O'Donnell, and Spyros Artavanis-Tsakonas, is funded by donations from individuals and the GSA. Applications, in the form of a fillable PDF form, were made available on the GSA web site in late October. The deadline for submitting the application and two letters of recommendation was November 28th. An on-line submission process was not possible this year because of the tight time frame, therefore we asked that the applications and letters of recommendation be sent to a gmail account set up for that purpose.

23

The Victoria Finnerty Awards Committee - Janis O'Donnell and Karen Hales and myselfhad a conference call on Friday, December 9 to review the applications and pick the "winners". We had 24 applications and we picked 6 recipients--spending out the entire fund of $4,000. The winners and their poster numbers are: Selma Avdagic, Saint Louis University School of Medicine—Poster 671B Samantha Galindo, University of Wisconsin Madison—Poster 971B Kenneth Hoehn, Duke University—Poster 428B Emily Hsieh, University of Washington, Seattle—Poster 483C Jacqueline McDermott, Hofstra University—Poster 730A Mohammad Siddiq, Indiana University, Bloomington—Poster 503B We would like to thank Liz Gavis and her assistant for generating the fillable PDF application and Phyllis Edelman of the GSA for administering the fund. In announcing the awards tonight, I will ask that people keep donating to this fund. In addition, I would suggest that the application deadline and the selection of the recipients be made prior to the abstract deadline. My guess is that the decision about which students to take to the Fly meeting happens early in the semester. The Selection Committee will rotate, with one old member leaving and new member joining each year.

12. Undergraduate Education Initiatives (Karen Hales) (Karen G. Hales, Primarily Undergraduate Institutions Representative) A Primarily Undergraduate Institutions (PUI) representative to the Fly Board has now been in place for two years. The ongoing goal is to facilitate enhancements to the Annual Drosophila Research Conference program, making the experience more productive for undergraduate students and their professors/PIs. The PUI representative has worked together with Beth Ruedi, GSA Director of Education and Professional Development, to design and implement several new initiatives for 2011 and 2012. Suzy Brown of the GSA has also provided essential help and support in these efforts. The annual PUI workshop, organized by rotating groups of PUI faculty since 2001, was the only undergraduate-oriented event until 2011. Four additional new events occurred in 2011: • Undergraduate Student Mixer • “Undergraduate Experience” program for invited students from local institutions and their professors • Education Special Interest Group Mixer for faculty interested in pedagogy, 24

•

Undergraduate Plenary, for undergraduate researchers attending the meeting, including one talk.

Reduced registration fees for undergraduates were instituted in 2010, along with an undergraduate poster contest category. More reliable methods for identifying undergraduate posters were implemented in 2011. Establishing travel awards for undergraduates was an additional goal. Fortunately, the inaugural year of the Victoria Finnerty Undergraduate Travel Award for the Drosophila Conference independently occurred in 2011-2012. The PUI representative served on the selection committee for this award. This award currently has no permanent endowment or funding source, so a future goal is to secure more stable funding. In 2012, all of the above initiatives are continuing, two with significant refinements: • The Undergraduate Plenary this year will include two speakers followed by a panel discussion with graduate students. This is intended for undergraduate researchers. • The “Undergraduate Experience” is renamed the “Genetics Conference Experience”, with further emphasis that this event is intended for local invited undergraduates who have not necessarily performed research before. One additional goal for a future year may be to establish a pedagogy workshop.

13. Asia-Pacific Drosophila Research Conference 2 (APDRC-2) in 2013, Seoul, Korea (Kwang-Wook Choi) The Drosophila community in the Asia-Pacific region has been growing. To promote interactions in the region, the APDRC committee (chaired by Dr. Yash Hiromi) decided to hold a regional Drosophila Research Conference every other year. Accordingly, the first APDRC was held successfully in May, 2011 in Taiwan (organized by Dr. Henry Sun). APDRC-2 will be held for 4 days in Seoul, Korea. We will invite a dozen PIs from USA and European countries and many more local PIs on 6 different sessions. APDRC2 will be an exciting conference with more than 450 expected participants. We hope that all board members and the fly community support us for continuing success of this regional conference.

14. Outreach and educating the public (Liz Gavis, Eric Baehrecke, others) Discussion point: In addition to hiring a science writer, the 2011 Board suggested the creation of a Board member position for coordinating outreach and education. Should we create such a position and how would we define the "job description"?

25

Update on UMAss initiative: on efforts by Eric, Victor Ambros and Ed Keohane (Vice Chancellor for Communications at UMass Medical) to produce a short video that educatee the public about the value of model systems research. Educational Initiatives Poster Session 892A Darwin Synthetic Interview and Horse Feet - Teaching Evolution through engagement and interactivity. John A. Pollock, David J. Lampe. Biological Sci, Duquesne Univ, Pittsburgh, PA. Hi Steve, I hope that all is well with you. I am writing because I see that you are helping to organize the Fly Meeting in Chicago this coming year. I am hoping to get an opportunity to give a presentation on education outreach to the public based on work that I have been doing for the last decade with NIH funding. The main thing I'd present is on teaching evolution, but will touch on other biological topics that I have covered in video games, planetarium shows and even a TV show. This last year my work was acknowledged with a Carnegie Science Award with Special Achievement in Education 2011. Last year I was invited to speak at the Robert Wood Johnson Foundation Games for Health Conference in Boston where some of my work was covered by the news paper USA Today. I am not trying to be boastful, but just trying to give a little perspective and to recognize that I feel that the Fly community would be uniquely receptive and interested. I am happy to work with a short talk and/or poster on the work, but would eagerly welcome an opportunity to speak in a longer format. Do you have any suggestions on how best to proceed? Should I just put in an abstract on the web site? Thanks John John Archie Pollock, Ph.D. Associate Professor of Biological Sciences Duquesne University 222 Mellon Hall Pittsburgh, PA 15282

26

[email protected] 412 855 4043 http://www.duq.edu/science/faculty/pollock.cfm http://www.sepa.duq.edu http://www.sepa.duq.edu/darwin/ www.ScientasticTV.com

15. White Paper (Denise Montell) Drosophila Board White Paper 2012 Explanatory Note: The first Drosophila White Paper was written in 1999. Revisions to this document were made in 2001, 2003, 2005, 2007 and 2009. The most recent past version is: http://flybase.bio.indiana.edu/static_pages/news/whitepapers/DrosBoardWP2009.pdf At its 2010 meeting, the Drosophila Board of Directors decided to write a new White Paper to include progress made in the preceding years and to assess current and future needs of the Drosophila research community. This draft was prepared by the Board, made available to the entire Drosophila research community, and modified according to feedback received from community members. The fruit fly, Drosophila, continues to occupy a central place in biomedical research. Our understanding of the basic principles of genetics, including the nature of the gene, genetic linkage, meiotic chromosome segregation, and recombination, all arose from studies in Drosophila. When recombinant DNA technology was developed in the 1970s, Drosophila DNA was among the first to be cloned and characterized, leading to pioneering studies that linked molecular lesions in the genome with mutant phenotypes in a multicellular animal. Over the ensuing decades, Drosophila research paved the way for our understanding of the central regulatory pathways that control animal development. Many of the signaling systems discovered through this research, such as Notch, Wnt, Hedgehog, Hippo, and Toll receptors, are now recognized as central contributing factors for major human diseases, including cancer, cardiovascular, diseases, and neurological disorders. Drugs targeting these pathways are in use or in clinical trials today. Thus Drosophila research provides an essential pipeline for discovery of drug targets and in some cases direct identification of drugs. Drosophila research has also defined not only molecules and pathways but also many fundamental biological processes that impact human health, including vasculogenesis, the innate immune response, stem cell determination and maintenance, cell and tissue polarity, growth control, pattern formation, circadian rhythms, sensory systems, learning and memory, neural pathfinding, and synaptic transmission. Drosophila thus serves as an outstanding organism for the modeling of human diseases, identifying molecular mechanisms and new therapeutic strategies for cancer and metastasis, chromosomal disorders, cognitive impairment and autism spectrum disorders, addiction to alcohol and drugs, heart disease, sleep disorders and neurodegenerative diseases including

27

Alzheimer’s, Parkinson’s, Huntington’s, motor neuron and neuromuscular disorders. Drosophila also serves as the closest genetic model for the major insect vectors of disease, such as Anopheles gambiae (malaria), Aedes aegypti (dengue fever, yellow fever), and Culex pipiens (West Nile fever), as well as many major agriculturally important insects, including pollinators such as honeybees and pests that include many species of beetles and aphids. Drosophila provides an excellent model for understanding the genetic basis of complex traits, providing insight into the importance of gene-gene and gene-environment interactions, and identifying genes and pathways relevant to orthologous complex traits in humans. In addition, the genus Drosophila has been a key model system for understanding population biology, the molecular basis of speciation, and evolution. A unique defining feature of Drosophila is its combination of rapid and facile genetics with a complex body plan and major organs and tissues that reflect the fundamental physiological, behavioral, and metabolic pathways in humans. Current technology allows researchers to manipulate the fly genome at a level of precision that exceeds that of any other multicellular genetic model system, from exact base changes by gene targeting to molecularly-defined chromosomal deficiencies and duplications. Single copy transposon insertions have long been routine in Drosophila, most recently with the added advantage of being able to target insertions to precise locations in the genome. With the genome sequences of multiple Drosophila species now at hand, the fruit fly also provides the best system for conducting studies of evolutionarily conserved regulatory networks, providing an ideal model for systems biology. Studies of Drosophila have provided fertile testing ground for new approaches in genomic research and continue to have a significant impact on biomedical research. Maintaining and expanding this tradition relies on the recognition by the scientific community and by the NIH that Drosophila remains central to our understanding of human biology and the origins of disease, and requires the support of key projects and facilities as well as the development of new technologies. To this end, the Drosophila research community has identified current bottlenecks to rapid progress and defined its most critical priorities for the next two years. We begin by first noting recent achievements that have been the most important for the community-at-large: • Completion of the Drosophila melanogaster genome (Release_5) through refinement in the sequencing of some highly repetitive regions dispersed in euchromatin, assembly of telomeric sequence on the 4th and X chromosomes as well as significant progress toward sequence finishing and assembly of 15 Mb of the moderately repetitive portion of the heterochromatin. • Updates to the Drosophila melanogaster gene annotation set (Release_5.22 as of 11/04/09). • Insights gained into gene and genome organization and evolution through the whole genome shotgun sequencing, assembly, alignment and annotation of the euchromatin of eleven additional Drosophila species: simulans, sechellia, yakuba,

28

erecta, ananassae, pseudoobscura, persimilis, willistoni, mojavensis, virilis, and grimshawi) • An expanding library of complete cDNAs and derivatives, including an expanding library of open reading frame (ORF) clones in a recombinational cloning vector. • An expanding collection of mutant strains with transposable element insertions or point mutations disrupting over 60% of the approximately 15,000 annotated genes. • Ten-fold expansion of the number of Drosophila cell lines available for study. • Expanded chromosome deletion collections providing near complete (>98%) genome coverage and finer subdivision of the genome with deletion breakpoints mapped to the sequence. • Continued successful use of RNA-interference (RNAi) in cultured cells, as well as development of related technologies and resources for cell screening and verification. • Development of RNAi technologies for whole animals, including expanding libraries for tissue-specific in vivo RNAi for the vast majority of fly genes. • Continued improvement of genetic techniques such as targeted gene disruption and the ability to integrate large fragments of genomic DNA into flies. • Production and distribution of GFP-based protein traps and enhancer traps in 900 genes. • Development of phiC31 integrase-mediated site-specific integration of transgenes to minimize position effects and reliably integrate DNA into the genome. • Genomic libraries for phiC31 integrase-mediated site-specific integration of large DNA fragments allowing rescue of almost any Drosophila mutation. • Transcriptional profiling of the complete life cycle and many tissue types. • Progress toward genome-wide tiling arrays and next generation sequencing platforms for comprehensive transcriptional profiling and genome-wide protein binding site mapping by ChIP. • Database development to integrate genome and genetic resources for Drosophila. • Expanding international stock resources, with over 100,000 publicly available stocks. These achievements have been accomplished through collaboration within the research community, to recognize and prioritize its most pressing needs. In addition, none of these projects could have been undertaken or completed without funding support provided, in whole or in part, by the NIH. Further progress in Drosophila research depends upon a continuation of this crucial collaboration. This White Paper represents an updated view of the most important priorities for near term future needs of the community. There is overwhelming agreement that two broad areas need to be supported and expanded to serve the Drosophila research community in the upcoming years. These are (I) basic community resources, consisting of Drosophila stock centers, electronic databases, and the molecular stock center, and (II) research support for functional analysis of the Drosophila genome, including characterization of temporal and spatial expression patterns for all Drosophila genes and proteins. These broad areas are described in detail below.

29

I) Basic Resources that Serve the Drosophila Community A) Stock centers providing a comprehensive range of genetically defined stocks are essential. i) D. melanogaster strains: Stock Centers are so central to research with Drosophila that their stability and improvement remain our highest priority for NIH infrastructure funding. Stock centers provide universal access to the genetic strains that are essential to research using Drosophila. Scientific progress builds on previous discoveries using new technologies, so it is necessary to keep relevant stocks in circulation while placing new stocks from large-scale resource development projects and individual investigators into public distribution in a timely manner. Dynamic stock collections are more challenging to manage than static collections, but collection contents must change continually if Drosophila experimentation is to retain its relevance and impact. As the complexity of stock collections increases, scientists will require more help optimizing research designs and locating appropriate strains. Also, as Drosophila gains more use by scientists who have little background in the field, stock centers will play an increasingly important role in making Drosophila genetics accessible to nonspecialists. Stock centers can satisfy informational demands through personal consultation and expanded website content while promoting effective resource use as long as user assistance remains a priority. Continued NIH support will assure that the needs of the Drosophila research community are met with vigorous stock acquisition, high quality collection curation, robust information management and generous user support. As described in the “Loss-of-function mutations” paragraph below, the fly community is ready to create multiple large-scale sets of versatile new stocks to support the functional analysis of the Drosophila genome. These stocks would be created for use by the whole community and should be housed in a public facility. Using guidelines that assure that only the most-needed stocks will be maintained, we estimate that a capacity of 50,000 stocks in the U.S. within the next five years is required to meet minimum community needs. Increased productivity and future technical developments are likely to necessitate additional capacity, however, and we anticipate that stockkeeping capacity within the U.S. will need to increase to 100,000 stocks to support Drosophila researchers for the foreseeable future. We therefore consider investment in increased stock center capacity as our highest priority for NIH infrastructure funding. The only D. melanogaster stock center in the U.S. that accepts new stocks is the Bloomington Drosophila Stock Center (BDSC). In its current facility at Indiana University, the BDSC can house a maximum of 35,000 strains. That capacity will be filled in the next 3-5 years, largely by expansion from ongoing NIHsponsored resource development projects, even after removal of several thousand strains whose usefulness has been largely superseded by newer stocks. While other solutions are possible, the most straightforward means of increasing stockkeeping capacity is expansion of the BDSC. The construction of new space or renovation of existing space at Indiana University would provide a long-term solution for the

30

Drosophila community to the problem of inadequate stock center capacity. ii) Other Drosophila species: The sequencing of 11 new species continues to drive demand for stocks of the twelve sequenced species and their relatives from the San Diego Stock Center at UCSD (SDSpSC). The SDSpSC currently maintains approximately 1,900 different stocks representing about 250 species, an increase of over 20% in the last year. Two hundred of these are newly created transgenic stocks in eight species. As additional genetically marked and transgenic stocks of these and other species are generated, the number of stocks will double in the next two to three years. While the SDSpSC’s space and infrastructure are adequate to accommodate the increase, the Center is already understaffed. Thus, at the very time when the role of the SDSpSC is even more central to the research community, insufficient staffing is compromising its function. B) Expanded and improved electronic databases to capture and organize Drosophila data, and integrate the information with other databases used by the research community. It is essential to support efforts that can keep pace with the enormous acquisition rate and increasing complexity of data being generated by Drosophila researchers. These include the sequence of eleven new Drosophila species, resequencing and deep phenotyping of hundreds of wild-derived inbred D. melanogaster strains, up-to-date gene annotations, the characterization of mutant phenotypes, RNA and protein expression profiles, and interacting gene, protein, RNA and small molecule networks. These efforts must also include effectively linking Drosophila databases with those of other organisms, including other well-established model systems and emerging systems for genome research. Not only will this development promote more rapid progress in Drosophila research, it should also significantly enhance progress in functional genomics overall by promoting crosstalk among scientists working in different fields. Up-to-date and well-organized electronic databases are essential conduits to translate information from fly research to other areas of study that can impact human health, including the study of human biology, genetic disease and biomedicine, cellular responses to infectious pathogens, and Dipteran disease vectors. C) Continued support for a molecular stock center that provides the community with fair and equal access to an expanding set of key molecular resources at affordable costs. The Drosophila Genomics Resources Center (DGRC) serves the community by collecting, maintaining and distributing valuable reagents that are utilized by labs throughout the world. Currently the DGRC houses an inventory of over 1,000,000 cDNA clones, transformation vectors, and clones in yeast as well as collections of vectors, fulllength cDNA clones, EST clones, and genomic libraries. The DGRC also carries 108 cell culture lines including embryonic lines from D. melanogaster and other Drosophila species, imaginal disc cell lines, and those derived from the central nervous system. Acquisition of these resources is possible through cooperation with large-scale projects, such as the Berkeley Drosophila Genome Project, as well as donations from individual labs that have generated collections of clones or developed new vectors, and donations from groups that have created new cell lines or wish to share existing unique cell lines. It is important to maintain a reliable, central molecular repository that is able to

31

expeditiously distribute key reagents to the scientific community as it can relieve individual labs of this responsibility and afford the end user with a dependable timeline for receiving materials. A central repository also ensures that these valuable resources are not degraded or lost, and provides technical guidance and ready access to reliable, relevant protocols. In addition, the importance of a molecular stock center is magnified by NIH guidelines that require investigators to make materials widely available. II) Research Support for Functional Analysis of the Drosophila Genome. A) Genetic resources: The most powerful advantage of Drosophila as a model system lies in the wide repertoire of genetic manipulations possible. Below we list the major current and future needs of the Drosophila community in continuing to support the goal of complete functional analysis of the Drosophila genome. i) Loss-of-function mutations: Central to all genetic studies in Drosophila is the ready availability of loss of function mutations in all genes, including insertion, deletion, point mutation and RNAi knock-down lines. The Genome Disruption Project (GDP) has tagged 60% of annotated genes with P-element, piggyBac and most recently, Minos insertions. Minos provides a broader spectrum of insertion sites, improving the yield of tagged genes. Also, insertions of a new Minos vector, MIMIC, can be modified by Recombination Mediated Cassette Exchange (RMCE) to allow tagging in vivo with any DNA element. This new strategy goes beyond generating mutations in protein coding genes. For example, it makes possible the generation of protein trap lines to reveal the temporal and spatial expression patterns and subcellular localization of thousands of proteins in vivo (see section C below). It also provides novel access to control sequences, structural DNAs, small RNA genes and the entire ensemble of currently unknown genetic elements. This new tool encompasses numerous applications that impinge on every aspect of fly research. In another approach, a first-generation collection of RNAi knock-down lines directed at all annotated genes has become available. Subsequently, technological improvements have been developed that result in more reliable and effective knock-down of any gene in any tissue, and secondgeneration collections of lines are now being generated. We strongly support continued NIH funding for insertional mutagenesis that allows RMCE tagging, for centralized RNAi screening, and for distribution of validated resources to the community. We encourage new funding opportunities for the development of RNAi resources in transgenic flies. In addition, creating collections of mutants that carry defined mutations on FRT-bearing chromosomes for thousands of genes represents a valuable step toward completing the functional analysis of the entire Drosophila genome. ii) RNAi screening in vivo: Conditional expression of hairpin constructs in vivo, known as tissue-specific RNAi, has made it possible to disrupt the activity of single genes with exquisite spatial and temporal resolution. The construction and distribution of libraries of transgenic RNAi lines, which can be targeted to specific regions of the genome to ensure consistent results, is an important resource for the community. We encourage continuing support for development of tissue-specific RNAi and related technologies and resources, including robust systems for RNAi in the germline as well

32

as support for maintenance and distribution of in vivo RNAi resources to the community. iii) RNAi screening in cells: The continued value of a centralized facility for conducting RNAi screens in cultured cells is clear from the experience of the NIGMSsupported Drosophila RNAi Screening Center (DRSC). Important improvements include: full-genome dsRNA libraries designed using current rules for minimizing offtarget effects and current gene annotations (coding and non-coding genes); availability of dsRNA libraries targeting specific classes of genes; improved image-based screens and analysis; primary cell screening; new and modified cell lines; RNAi “rescue” with D. pseudoobscura and D. persimilis fosmids (making use of resources generated for genome sequencing), ongoing production of a library for overexpression screening (derived from the community cDNA collection), and production of reagents for both loss and gain of function microRNAs and non-coding RNAs. The utility of RNAi screen results is evident in the large number of publications on individual screens and also in recent bioinformatics analyses based on full-genome RNAi datasets in the DRSC database. The community supports continued funding of the DRSC and further development of new cell screening technologies (including new cell lines and new methods for limiting false positive and false negative results), and for the distribution of data and resources to the community. iv) cDNA resources: Comprehensive cDNA sequences for D. melanogaster will be of enormous use for gene annotations and expression studies, at the level of individual genes or on a genome-wide scale using microarrays. Ongoing efforts to obtain and sequence full-length cDNAs should be supported. These, in turn, can be used to generate high quality libraries of expressionready cDNA clones that represent the full complement of Drosophila protein-coding genes. The insertion of these cDNAs into appropriate vectors for proteome and ribonome studies is a high priority. Currently 10,000 expression-ready sequence-verified constructs for 5,000 genes have been produced. Approximately 10,000 expression clones have been made and are being used for expression studies in tissue culture and in flies. These resources are being used to generate a protein-protein interaction map of Drosophila and will facilitate the analysis of DNA-protein and RNA-protein interactions. In addition to these studies, the complete cDNA set provides a basis for the production of antibodies against Drosophila proteins, which represents a high-priority need of the community. B) Functional annotation of Drosophila genomes. i) Sequencing of additional genomes: Thanks to four separate National Human Genome Research Institute (NHGRI) funded initiatives, the sequence of 11 additional species of Drosophila is now complete. Although an important accomplishment, this work needs to be extended to obtain high quality finished genome sequences for the melanogaster group species (D. simulans, D. sechellia, D. mauritiana, D. yakuba, D. santomea, and D. erecta). These new data will continue to present an unparalleled opportunity for rapid progress in a range of areas including (1) using comparative sequence analysis to improve the annotations of D. melanogaster, (2) understanding genome evolution including the functional evolution of genetic pathways, (3) describing variation at a genome-wide scale, (4) identifying non-coding genes and regulatory

33

elements, and (5) investigating differences between recently diverged species that produce interfertile hybrids. To fully realize the potential of this unique resource, continuing support is needed for assembling, aligning and annotating these genomes. ii) Additional resources for sequenced genomes: There is also widespread agreement that the community would be well served by having at least one good genomic library available for each of the 12 sequenced Drosophila species. The choice that has emerged is a P[acman] BAC library with 40 kb +/- 5 kb insert size, aiming for ~12X coverage. These genomic clones will be used for finishing the genome sequence, allowing the rescue of mutants in different species, and providing evidence for RNAi specificity in other species. They will also allow tagging of genes to determine gene expression patterns and numerous other applications. In addition, projects aimed at sequencing ESTs and cDNA clones for selected species will be invaluable for refining annotations and for developing resources to leverage the new sequence information, such as species-specific microarrays, and high-density SNP genotyping methods for speciation studies. Finally, with NextGen sequencing technologies, upgrading the sequences of the already-sequenced genomes at relatively low cost to fill in gaps and extend long-range contiguity would be valuable to researchers studying these species or using them for comparative analysis. iii) Genome-wide variation in D. melanogaster: A high priority for further annotating the Drosophila genome will be to obtain high quality whole genome sequences of a large number of D. melanogaster inbred reference strains. Understanding the effects of natural single nucleotide and copy number variants on a wide range of complex phenotypes, including variation in gene expression, will add a more subtle dimension to genome annotation that will complement other functional studies. Whole genome association studies of Drosophila complex traits using several hundred wild-derived strains is an efficient method of genome annotation, particularly for traits, such as behaviors, that are difficult to quantify precisely in high throughput assays. This strategy is unbiased, and includes non-coding genome regions as well as protein coding regions. These complex traits are directly relevant to human health and adaptive evolution. iv) Genome-scale analysis of DNA elements: DNA element characterizations of great importance to the community include the identification of all sequence-based functional elements associated with both protein coding and non-protein coding transcribed sequences, characterization of transcription factor binding sites throughout the genome, identification of other binding sites for chromosomal proteins, and locations of various types of epigenetic modifications, origins of DNA replication, and other structural features of the D. melanogaster genome. We endorse the value of genomescale analysis of functional DNA elements in D. melanogaster and urge continued funding for such efforts. v) Completion of the mapping, sequencing, and annotation of D. melanogaster heterochromatin: The difficulty of assembling heterochromatin remains the major roadblock toward the completion of genome projects in most multicellular organisms.

34

Mapping, sequencing, and annotation of heterochromatin is essential for genome-wide analyses, such as mapping the distributions of transcription factors and chromatin components, non-protein coding RNAs, and RNAi-mediated gene disruption screens. In addition, elucidating heterochromatin organization is key to understanding the epigenetic regulation of gene expression, with immediate implications in developmental biology and medicine. Important information about the composition and organization of Drosophila heterochromatin has been generated through detailed assembly of existing middle repetitive sequences from whole genome shotgun with targeted finishing using BAC-based strategies. Annotation of these revealed that ~3% of all Drosophila proteincoding genes reside in heterochromatin. However, much of the satellite sequence is unmapped and unfinished, and reliable annotations require more complete information. While one of the roadblocks has been the availability of techniques to assemble the highly repeated sequences of heterochromatin, as such capability emerges from new sequencing technologies, we urge funding of the application of these technologies to the assembly and annotation of the heterochromatin of D. melanogaster. C) Capturing temporal and spatial expression patterns for all Drosophila genes and proteins. Documenting the expression of all transcripts and proteins at single cell resolution will be essential to fully understand the structure and function of the Drosophila genome. Although the spatial expression pattern of over 7,500 genes has been determined by in situ hybridization to embryos, this effort needs to be completed for the remaining genes, extended to other stages in the life cycle, and done in a few key mutant backgrounds. New attention should be focused on in situ mapping of the expression patterns of Drosophila RNA genes, including those encoding the expanding number of small RNA classes, such as piRNAs. Protein-trap technology, which allows the modification of endogenous genes to produce GFP fusion proteins in vivo, has been shown to provide accurate information on normal expression patterns and subcellular localization. An ideal approach toward this goal involves the establishment of a large collection of modifiable protein-trap strains that can be converted through RCME to any marker, including markers that can be used for live imaging, Chip-seq, immunoprecipitation, transmission electron microscopy or in vivo protein inactivation. New opportunities should be exploited to generate large sets of such fusion genes in vitro by recombineering, and to introduce them along with sufficient flanking DNA into specific sites supporting faithful expression using phiC31-mediated swapping. Genomic libraries in P[acman] are now available that should greatly facilitate the generation of these fusion transgenes. Support for the generation, maintenance and distribution of these lines to the community is a high priority, due to their versatility and widespread value. Antibodies represent a high priority for future development. They continue to provide an essential tool for expression profiling, biochemical analyses, and are synergistic with protein traps and labeled transgenes described above. Speeding the production of antibodies against large numbers of Drosophila proteins is essential. A pilot project should be funded to prove that a centralized production facility could economically generate a significant panel of high quality monoclonal and polyclonal antibodies against important classes of proteins. Support to maintain and distribute expression reagents directly to the research community remains essential. Efforts to record and systematize protein expression patterns for electronic

35

distribution should also be expanded. The value of such databases will increase with each improvement in resolution and breadth of coverage. Projects that combine biological expertise with sophisticated imaging methods that can capture dynamic multichannel expression patterns in four dimensions, and with sub-cellular resolution, should be given high priority and supported for at least a few key tissues.

16. Bloomington Stock Center (Kathy Matthews, Kevin Cook) (Kathy Matthews, Kevin Cook, Annette Parks, Thom Kaufman) • • • • •

•

•

•

•

Stocks held: 38,504 Registered user groups: 2,631 Registered users: 5,731 Shipped in 2011: 214,718 subcultures in 14,540 shipments Funding: o We are in year 3 of a 5 year grant from NSF+NIH, ~$464,500 direct costs this year. Based on Jan & Feb orders we project fee income of approximately $722,000 (excludes postage & courier charges) in 2012. Increased income from user fees is paying for the growth of the collection. Growth: o Renovations funded by HHMI were completed in 2011, providing us with space for 60,000 – 70,000 stocks. o 7,882 stocks were accessioned in 2011. o Stockkeeping staff grew from 29 employees providing 16 FTE (full time equivalents) to 34 employees providing 18 FTE. Management/scientific staff remains at 3.8 employees providing 5-6 FTE and needs to be expanded. Costs: o Stock accession & maintenance account for ~70% of costs. § Average accession cost per stock: ~$28 § Average annual maintenance cost per stock: ~$24 o Stock distribution accounts for ~30% of costs. o Our annual expenses exceeded annual income for each of the last two years. Cost recovery: o A new accounts system using a more traditional business model was introduced in 2011. We support four account types to provide some flexibility, but all require a purchase order or payment prior to shipment. Unfortunately, the transition for existing accounts has been more difficult than we anticipated and we have some unhappy users. We regret their distress, but the changes were needed and we think things will smooth out once people are used to the new system (new accounts have worked well). o Fees for 2012 are expected to increase fee income by ~20%. This significant increase was needed to bring income in line with expenses, including needed additions to our staff. New stocks: We expect to add 7,080–10,130 new stocks in 2012. o 3,480 GAL4 drivers reflecting enhancer expression from the Rubin lab 36

•

•

o 500–3,000 insertions of RNAi constructs from the TRiP o 2,150 insertions via the GDP pipeline o 550–1,000 FlyTrap stocks (flytrap.med.yale.edu) o 400–500 stocks in all categories from the community at large Pruning: We will continue to remove obsolete, redundant and selected low-use stocks from the collection in 2012. 672 low use stocks with P{wHy} insertions were recently removed. We also intend to prune ANTC and BXC alleles, and redundant insertion alleles on the X chromosome. Mites: The mites discovered in several hundred vials in one of our constant temperature rooms in August 2011 were a species from the Family Tarsonemidae never before reported in Drosophila cultures. We suspended shipments for a week while we assessed the problem. When we were convinced the infestation was confined, we resumed shipments of all stocks except the ~11,500 stocks occupying the affected room. New cultures of all ~11,500 potentially contaminated stocks were established on miticide-treated food as back-ups. We then phenotype checked and expanded the duplicate copies of the affected stocks to create clean new main copies. We cleaned up contaminated cultures only when the duplicate’s phenotype was incorrect or it was sick. Most stocks were available for reordering by the end of August, but some high-demand and weak stocks were unavailable until the end of September. Unfortunately, the scale of contamination was large and the effort to combat it was enormous. This crisis monopolized our time for nearly two months and incurred considerable extra expense. We have provided additional training in mite recognition and we have instituted a new system of culture surveillance. SAB: Current members of our Scientific Advisory Board are: o Hugo Bellen, Baylor College of Medicine (Chair) o Norbert Perrimon, Harvard Medical School o Ken Burtis, University of California, Davis o Susan Parkhurst, Fred Hutchinson Cancer Research Center o Nancy Bonini, University of Pennsylvania

17. Kyoto Stock Center (DGRC: Drosophila Genetic Resource Center at KIT) (Masa Itoh) (Masanobu Itoh, Toshiyuki Takano-Shimizu-K) The DGRC was established in the Kyoto Institute of Technology in1999. We hold more than 27,000 stocks, and 25,600 are currently available for worldwide distribution. We have stocks for the GAL4/UAS system, protein trap analysis, imaging analysis, mosaic analysis, and genome-wide deficiencies and duplications. Subcultures are shipped by EMS (Express Mail Service of the Japan Post Office) or by airmail (small packet). We also accept donations of useful new fly lines from the community. Please contact us at: http://kyotofly.kit.jp/cgi-bin/stocks/webmail_usr.cgi. Prof. Masa-Toshi Yamamoto is retiring. As of April 1, 2012, the new staff will include Toshiyuki Takano-Shimizu-K (chief, professor), Masatoshi Tomaru (assistant professor), 37

and Masanobu Itoh (director). The DGRC continues without change in its basic policy as a stock center. The DGRC is one of the four members of a Drosophila stock center consortium funded by the “National BioResource Project” (NBRP) of the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan. The consortium also includes National Institute of Genetics (NIG) for 12,600 stocks of RNAi fly library and Ehime University and Kyorin University for 2,200 strains of Drosophila species.

18. Indian Stock Center (K. VijayRaghavan) The Indian Drosophila research community has around 50 groups scattered in different organisations and the number is increasing slowly but steadily. Those institutions such as the National Centre for Biological Sciences ( NCBS, Tata Institute of Fundamental Research) where there is a substantial concentraion of reserachers, get their fly stocks from Bloomington, VDRC etc. Our stock center maintains these only for internal use of the groups which ordered them and they are not subsequently distributed. Ocasionally, if smaller institutions do not have credit card facilities , are unable to pay, or are unable to deal with postal customs, we order on their behalf: We order afresh even if the stocks are already with us and send the fly vials unopened to their destinatiion. In collaboration with the groups of Sue Celniker and Spyros Atravanis-Tsakonas we have derived several thousand UAS- HA-tagged CDNA strains as part of a Drosophila proteome project. We maintain these stocks and currently distribute them at no cost other than the provision of a FedEx number. Our requests are growing and we may have to charge nominally sometime in the not-so-distant future. We are embarking on another project that will generate may strains locally and will be happy to serve as a repository for these and to distribut them. We are also happy to be considered to being a repository for others stocks that the fly community would like us to keep: We are now well set to do this if you think there is a need. My personal view is that the Indian science agencies and NCBS for sure will be committed to a long-term support for a stock center. Mailing out stocks from India works well, so we could share the responsibility for the community needs in a manner complementary to other efforts.

19. Drosophila Species Stock Center (Teri Markow) (Therese Markow & Maxi Richmond, University of California at San Diego) Collection Overview The Drosophila Species Stock Center (DSSC) collection currently consists of 1535 living stocks, representing 227 species. In 2011, the DSSC added 35 new stocks 38

from 18 species. Seven of the new stocks are in the Drosophila subgenus Zaprionus and were kindly donated by Jean David at the Centre National de la Recherche Scientifique in France. The rest of the new stocks were donated by Dr. Masayoshi Watada (Ehime University, Japan), Darren Obbard (University of Edinburgh, UK), and Dan Lindsley (University of California, San Diego). We also decommissioned 61 stocks that were not frequently ordered from species with strong representation in the collection. There were 5 additional stocks lost in 2011. Genomic DNA is available for all 12 species that were part of the 12 genomes consortium, as well as nine additional species with recently published genomes (more below). We also have DNA available for three commonly ordered stocks: D. miranda, D. teissieri, D. orena, and have created three genomic “DNA packs” for 1) the D. virilis group, 2) a global representation of D. melanogaster, and 3) the D. mojavensis species cluster. Nine additional Drosophila species have publicly available genome sequences that have recently been released. Dr. Peter Andolfatto’s lab at Princeton University has released the genome of Drosophila santomea using a stock that is currently maintained in the center (14021‑0271.01). In addition, as part of the modENCODE project, the Baylor College of Medicine has released genome sequences for D. eugracilis, D. rhopaloa, D. biarmipes, D. bipectinata, D. elegans, D. ficusphila, D. kikkawai, and D. takahashii. All eight of these stocks are available in the DSSC. The phylogenetic relationships of all 21 sequenced species are illustrated in Figure 1. The DSSC always has consisted of a permanent collection of both ethanol-stored and living stocks. As of February 2012 (when this report was submitted), the 1535 cultures in the living collection consist of 1030 wild-type stocks (both multi-female and isofemale lines), 354 mutant allele stocks, and 151 transgenic stocks. The living collection represents a diversity of 227 species. On the other hand, the 502 stocks in the ethanol-stored collection contain 418 wild type, 39 mutant, and 45 transgenic stocks. We periodically offer, on a temporary basis, a varying number of recently caught isofemale wild-type cultures. These isofemale collections are subsequently made “permanently available” by storing adults in ethanol or in the -80°C freezer. Summary of Order History In 2011, the DSSC provided the Drosophila research community with 1,030 stocks in 247 shipments representing 65% of species in the Stock Center. 29% of the orders came from international institutions. Details of the stock sales for 2010 and 2011 are presented in Table 1 below. The genome-sequenced species’ cultures presented approximately 19.5% of stocks sold. The top 20 species requested represent 57% of the total stocks sold by the DSSC, and are listed in Tables 2 and 3. While the number of US orders was similar between 2010 and 2011, international orders decreased. In addition, the number of stocks/order in both domestic and international orders decreased in 2011. The most commonly ordered genomic DNA was for the genome stocks of D. melanogaster, followed by D. grimshawi (of which there are only 9 vials left), D. mojavensis, and D. sechellia. There has been one order for the D. melanogaster world-wide “DNA pack” consisting of DNA from 13 D. melanogaster stocks from around the world. 39

Quality Control As a means of instituting new quality control methods in the DSSC, we have been working with Paul Hebert and the Barcode of Life project at the University of Guelph (Canada) and have generated COI barcode sequences for nearly all wild-type stocks in the Stock Center. This project also establishes a record for each stock in the Barcode of Life Database (BOLD) that includes an image and geographic data from all known collections of the species. We are in the process of linking each record in the Stock Center database to the records established in BOLD. Using the COI data garnered from this project, we have thus far detected three cases of crosscontamination between D. melanogaster and D. simulans, and five cases of stocks that were misidentified or had nomenclature changes. Workshop In 2010, funding did not allow us to conduct the annual and very popular species workshop, but we were able to offer it again in 2011. The workshop mechanism, which familiarizes researchers with the attributes of a range of species, has been a major driver in the community’s ability to take advantage of the variation in the genus and thus in the demand for stocks. We plan to offer the workshop again in 2012 and are working with our development officer to find corporate sponsors so that funding will not be the issue it has been. NSF and Living Collections Our support from the Living Collections Program at NSF was renewed for four years last spring, with declining budgets each year. The NSF indicated that foundation priorities were moving away from supporting living collections and that the collections should consider moving to a more “business-type” model. This would greatly increase costs and require that rare but interesting stocks be decommissioned. Had this been the case earlier, some species that now have been sequenced would have been lost to the community. In an effort to improve the business aspect of the DSSC, we have initiated a Facebook page to increase visibility and accessibility to the stocks available in the DSSC. We feature a ‘fly of the month’ and post information about its life history traits, interesting research papers, and videos of its mating behavior. All orders placed receive a sample of the fly of the month consisting of 5-6 flies so that researchers have an opportunity to see and experience the diversity of the DSSC collection.

40

Table 1: Shipment totals

# Orders USA INT Total # Stocks USA INT Total

1172

2010

2011

173 81 254

176 71 247

799 373

742 288

1030

Tables 2 and 3. Top 20 species ordered in 2010 and 2011 Rank st 1 nd 2 rd 3 th 4 th 5 th 6 th 7 th 8 th 9 th 10 th 11 th 12 th 13 th 14 th 15 th 16 th 17 th 18 th 19

Species D. simulans D. sechellia D. melanogaster D. pseudoobscura D. ananassae D. yakuba D. virilis D. willistoni D. mojavensis D. mauritiana D. persimilis D. erecta D. teissieri D. santomea D. mercatorum D. arizonae D. immigrans D. novomexicana D. montana

Rank st 1 nd 2 rd 3 th 4 th 5 th 6 th 7 th 8 th 9 th 10 th 11 th 12 th 13 th 14 th 15 th 16 th 17 th 18 th 19 th 20

2010

109 68 66 62 41 41 39 38 36 29 28 24 15 14 13 9 8 8 7

41

Species D. melanogaster D. virilis D. simulans D. sechellia D. pseudoobscura D. mauritiana D. mojavensis D. ananassae D. willistoni D. yakuba D. erecta D. subobscura D. persimilis D. arizonae D. suzukii D. nannoptera D. miranda D. orena D. americana D. hydei

2011

123 84 64 57 41 34 30 24 21 19 14 12 10 8 8 7 7 7 7 6

Figure 1. Phylogeny of Drosophila species with sequenced genomes

20. Mexican Drosophila Species Stock Center (Juan Riesgo-Escovar) The stock center, which was very recently founded, will house Mexican Drosophila species collected from the wild, and also hold back-up copies of the twelve Drosophila species whose genomes were sequenced, besides copies of Mexican species housed at the Drosophila Species Stock Center in San Diego. It will also very shortly have a collection of fixed material, together with collection data, available on site, and on the web. Its intention is to try and make all materials available to the Drosophila research community at large.

21. Berkeley Drosophila Genome Project (Sue Celniker) (Susan Celniker, Ann Hammonds, Ken Wan, Erwin Frise and Roger Hoskins) A. Introduction The BDGP was established in 1992 to sequence the Drosophila melanogaster genome. Now in our twentieth year, we continue to expand activities with the goals of improving the functional annotation of the genome and expanding community resources. Since the sequencing of the euchromatic portion of the genome, we have continued to work on assembly and finishing of the heterochromatin and have moved into functional genomics. We have recently completed a draft version of Release 6 of the genome and are now performing final quality control checks in preparation for public release. We continue to characterize the transcriptome using next generation RNA sequencing and to validate gene and transcript models by analysis of full-length cDNAs. We continue to

42

use the cDNAs to generate resources for proteomics studies and as templates for probes to determine spatiotemporal gene expression patterns in the embryo. B. Clone Resources To date we have submitted DNA sequence for 258,483 cDNA clones, of which 21,466 were fully sequenced and 16,473 fully support a FlyBase release 5.32 protein model. The Gold Collection of cDNAs whose amino acid translation matches a FlyBase model with 100% identity, now contains 11,181 clones. From the Gold Collection, we have produced 8,602 expression-ready donor clones lacking the native stop codon (for making C-terminal fusion constructs) and 8,459 expression-ready donor clones containing the native stop codon (for making N-terminal fusion constructs). Using the donor clones, we have generated sets of expression clones in different vectors with a variety of tags (Table 1). Table 1. Summary of Expression Clones. Collection

Vector

Promoter

XO XS MXO

pDNR-Dual pDNR-Dual pMK33CTAP-BD pMK33CFH-BD pUASTCFLAGHABD-PHI pUAST-CmCherryBDatt pUAST-CeGFP-BDatt pUAST-NmCherryBDatt pUAST-NeGFP-BDatt

FMO UFO

URO

UGO URS

UGS

N-term Tag

C-term Tag

ORF Stop Codon?

System

T7 T7 Metallothionein

----

6XHN -TAP

No Yes No

Metallothionein

--

Flag-HA

No

UAS

--

Flag-HA

No

E. coli E. coli Cell culture Cell culture Gal4UAS

UAS

--

mCherry

No

UAS

--

eGFP

No

UAS

mCherry

--

Yes

UAS

eGFP

--

Yes

2

Past year (3/113/12) 761 951 0

Total

773

7876

2211

6102

Gal4UAS

0

257

Gal4UAS Gal4UAS

0

248

0

250

Gal4UAS

0

242

8602 8459 1961

Table 2. Summary of clones available at the DGRC: Collection Past year (2010MarCumulative 2011Mar) AU (Gold) 2,016 ready to ship 11,181 XO 1,248 ready to ship 7715 XS 2,016 (480 more ready to 7093 ship) MXO 0 1961 FMO 1,229 ready to ship 7103 UFO 2,331 ready to ship 3891

C. Embryonic Gene Expression We continue to collect embryonic spatiotemporal gene expression data from high throughput in situ hybridizations using the Gold Collection clones as templates for RNA probes. In the coming year, we plan to add expression patterns for CRM-driven reporter constructs from the Rubin/Janelia collection. In 2010, we redesigned our gene expression patterns database to facilitate the transfer of expression pattern images and controlled vocabulary annotations from our production pipeline to the public database (http://insitu.fruitfly.org) and to add new search and discovery tools based on computational image analysis. We are active participants in the development of the open source image analysis platform FIJI (fiji.lbl.gov). To date we have examined 8460 genes and documented their expression patterns with over 150,000 images. D. Other Resources In an effort to improve the quality of our web-based user support, we have made changes to our website (http://www.fruitfly.org) including: updated FAQs, updated protocols and an updated design to make it easier for users to navigate to the relevant information. We have also added software for users to generate complete plasmid maps for expression clones. In addition we have added a search function so that users can identify all expression clones for a particular gene. We continue to work with FlyBase to improve gene and transcript annotations. We continually submit clones to the DGRC molecular stock center for distribution to the community. E. Technology cDNA and expression clone sequencing continues to rely heavily on the ABI3730xl capillary sequencer. Characterization of the transcriptome as part of the modENCODE project has primarily been on the Illumina GAII and HiSeq platforms. We note that sequencing technology continues to evolve rapidly, and access to the latest instruments is essential to our mission. F. Funding The BDGP is funded solely by NIH grants (NHGRI and NIGMS). The P41 (SEC) was refunded as of April 1, 2011 to continue to generate expression-ready cDNA resources

3

for three years. An R01 (SEC) funds the spatiotemporal expression studies for two more years. Informatics support for the spatiotemporal expression studies is now funded through an NIH BISTI grant to Erwin Frise. The modENCODE project will continue for one year in a no-cost extension of an NHGRI U01 (SEC).

22. modENCODE Project (Sue Celniker) (Susan Celniker, Steven Henikoff, Gary Karpen, Manolis Kellis, Eric Lai, David MacAlpine, Brian Oliver and Kevin White) A. Introduction The modENCODE project grew from a White Paper written in 2006. Grants were solicited and awards made in April of 2007. Six research proposals were funded in addition to a data distribution center and more recently a data analysis center. A marker paper was published in Nature in 2009 and a series of publications in Science, Nature, NSMB and Genome Research in 2010 and 2011. We were given a fifth year of funding to complete proposed studies and to expand studies within the limits of the original aims to determine the function of every base in the genome. The project has been very successful. NHGRI has folded any continuing work in model organisms into the ENCODE project. New proposals were submitted in November 2011 and the results of review will be known at the end of March 2012. The priorities are for studies in human, mouse then the model organisms. At least two proposals were submitted concerning Drosophila, one to finish the characterization of transcription factor binding sites in worms and flies using tagged transcription factors and the other to study RNA-binding proteins in flies using the S2 system and RIP-seq. Community support will greatly facilitate moving forward with ENCODE. B. Transcription The Celniker group has continued to to work toward a comprehensive characterization of the Drosophila melanogaster transcriptome. We have sequenced strand-specific, paired-end poly(A)+ RNA libraries from 30 developmental stages, 25 cell lines, 29 dissected tissues, 27 environmental and chemical perturbations. We have also generated rRNA-depleted poly(A)- RNA-Seq data for a subset of the RNA samples from the developmentl stages. In total, we have produced ~22 billion mapped RNA-Seq reads. This is more than ten times as much data as published (Graveley et al., 2011). To assist with transcript modeling using the RNA-Seq data, we have produced CAGE (Cap Analysis of Gene Expression) data to map 5’ transcription start sites within promoters in 42 of the RNA samples, producing at least 5M mapped reads per sample. These new data greatly expand on the characterization of promoter elements described in (Hoskins et al., 2011). To define polyadenylation sites, we performed RNA-Seq on libraries re-amplified with oligo-dT primers. We are now using these data to model fulllength transcript structures and quantify their expression levels using custom software. Our goal is to provide an improved annotation of the genome that is supported by empirical evidence. In addition, we are studying RNA binding proteins involved in splicing (Brooks et al., 2011) Alternative splicing is an important means of increasing protein diversity and regulating gene regulation. We have individually depleted 58 RNA 4

binding proteins and performed 30 RIP-Seq experiments in S2 cells. We have identified tens of thousands of new alternative splicing events revealing that over 60% of Drosophila pre-mRNAs are alternatively spliced. We have also identified thousands of splicing events that are regulated in a tissue- and sex-specific manner. The RNAi and RIP-Seq data has allowed us to identify splicing events that are directly and indirectly regulated by individual RNA binding proteins allowing us to begin elucidating the alternative splicing regulatory networks in Drosophila. Together, these studies provide tremendous new insight into the extraordinary diversity and regulation of alternative splicing in Drosophila. The Oliver group worked with the Celniker group on the production and analysis of polyA+RNA sequence and has brought comparative analysis to the modENCODE project. They isolated and sequenced polyA+ RNAs from adult male and female heads from D. pseudoobscura and D. mojavensis, as well whole females and males of D. ananassae, D. mojavensis, D. pseudoobscura, D. simulans, D. virilis, and D. yakuba. The Lai group has continued to sequence many small RNA libraries that cover new cell/tissue sources and combination of mutant backgrounds and Ago immunoprecipitations. These data fueled insights into the sorting of endo-siRNAs (Okamura MCB 2011), discovery of many new mirtrons (Chung Gen Research 2011) and allowed a major reannotation of canonical miRNAs, their variants and their modifications (Berezikov Gen Research 2011). Most recently, collaborative analysis of the transcriptome by the Celniker and Lai groups has led to the recognition of broad tissue-specific patterns of alternative polyadenylation (Smibert and Miura et al, Cell Reports 2012). This includes neural-specific 3' UTR extensions to hundreds of gene models, which collectively bring them under the influence of unexpected posttranscriptional control by miRNAs and presumably other RNA binding proteins. C. Chromatin The Karpen group has published three papers describing 1) the basic mapping of histone modifications and chromosomal proteins and an analysis of combinatorial chromatin states (Kharchenko et al., Nature 2010), 2) analysis of the plasticity of epigenetic marks in heterochromatin (Riddle et al., Genome Research 2011, and 3) a comprehensive analysis of the specificity of commercially available histone modification antibodies with an accompanying web site for public access to the data and opportunities to upload information from other labs (in collaboration with the Lieb and Ren groups), in addition to contributing chromatin data and analyses to the integrative paper (modENCODE consortium et al., Science 2010). We are currently completing the mapping and analysis of chromatin ‘landscapes’ for 75 proteins and marks in five tissue sources (early and late embryos, Kc, S2 and BG3 cell lines, which we expect to complete by the end of year 5. The Henikoff group has previously demonstrated cell-type-specific epigenomic profiling by expression a nuclear envelope protein under control of a tissue-specific promoter and isolation of tagged nuclei using affinity purification on magnetic beads. This was done in Arabidopsis, and for modENCODE, we have recently successfully adapted this strategy to flies and worms (Steiner et al., Genome Research 2012). Our project has also used RNAi knockdowns of chromatin regulators to catalog changes in chromatin properties using salt-fractionation of chromatin and CATCH-IT, a novel

5

metabolic labeling method that we introduced for measuring nucleosome turnover. We have found that single-base-pair resolution of nucleosomal and sub-nucleosomal landscapes can be achieved for low-salt-soluble classical active chromatin, including paused RNA Polymerase II (Teves & Henikoff, Genes & Development, 2011). Combining these technologies to obtain a single base pair resolution map of the entire Drosophila and worm epigenome for selected cell types is the current goal of our modENCODE project. D. Replication The MacAlpine group has characterized the DNA replication program using multiple genomic approaches which include replication timing, origin mapping and binding sites of essential replication initiation factors (MacAlpine et al., 2010, Eaton et al., 2011). A key finding of these studies was that chromatin environment was predictive of origin function. The MacAlpine group is currently mapping replication intermediates and ORC binding sites during development. The Orr-Weaver group examined the differential replication of multiple polytene tissues and identified tissue specific regions of differential replication including amplicons and under-replicated regions that are coupled to transcriptional regulation in some but not all of the tissues (Nordman et al., 2011, Sher et al., 2012). The Orr-weaver group is continuing to profile distinct tissues for differential replication. E. Cis-regulation The White group has continued to perform ChIP seq experiments, prioritizing factors requested by the community on the modENCODE web pages or through direct contact. To date, over 350 datasets have been produced by this project and are publicly available. Analyses of these data have revealed the organization of insulators, dynamic chromatin markings during development, more than 150,000 transcription factor binding sites representing over 35,000 unique locations, signatures of enhancers and promoters (Negre PLoS Genetics 2010; Negre Nature 2011). More than 1,500 novel promoter predictions have been validated in cell culture and by comparing to CAGE data from the Celniker group and Hoskins et al. 2011, as well as dozens of predicted enhancers (Hoskins Gen Research 2011; Negre Nature 2011). Working with Hugo Bellen's group, a community BAC resource was developed and epitope tagging applied to ChIP and imaging, and strains are released to the Drosophila stock center as they are validated (Venken et al. Nat Methods 2009). Future work will continue to focus on producing ChIP seq data to provide tissue-specific maps of the regulatory architecture of the genome. F. Funding modENCODE is funded solely by NHGRI U01 grants.

6

23. Drosophila Gene Disruption Project (GDP) (Hugo Bellen) (Hoskins, Spradling, Bellen) The Drosophila Gene Disruption Project (GDP) has created a widely used, publicly available collection of transposon insertion mutants (Bellen et al., 2011; Spradling et al., 2011). We are continuing to expand the collection using new tools that will dramatically increase its utility. We have developed a versatile Minos transposon, named Mi{MIC}, that contains two phage φC31 attP sites for site-specific recombination flanking a genetrap cassette. Mi{MIC} inserts in coding introns, allowing Recombination Mediated Cassette Exchange (RMCE) to swap the gene-trap cassette with any other DNA cassette to create genes expressing custom tagged fusion proteins. We have developed a battery of such cassettes for protein tagging for visualizing expression patterns in fixed or live animals, chromatin immunoprecipitation-sequencing for transcription factor binding studies, and immunoprecipitation-mass spectrometry for analysis of protein complexes (Venken et al., 2011). To utilize the power of Mi{MIC} technology fully, a pre-existing insertion in or near the gene or genomic region of interest is required. This should allow us to modify nearby genes using homologous recombination (Gao et al. 2008). We are expanding our collection of Mi{MIC} insertion stocks and bring the approaches outlined above to bear on more than 95% of Drosophila genes and euchromatic regions. We have already created 8,000 Mi{MIC} lines. We aim at creating an additional 10-12,000 lines that will tile the genome with insertions spaced no more than about 40 kb apart. Moreover, the lines will be directly associated with an estimated 5,500 genes, of which an estimated 2,800 genes will have an insertion in a coding intron. We are utilizing the newly generated Mi{MIC} lines with intronic insertions to produce strains with functional protein trap (gene-reporter) fusions in at least 1,000 of the highest priority genes for immediate use by the community. We have currently created the first 50 such lines, and they are being characterized. These lines will more than double the current number of tagged fusion genes. In sum, the proposed collection of Mi{MIC} insertions spaced throughout the genome will move virtually every aspect of Drosophila genetics to a higher plateau unmatched by any other metazoan model organism. Currently almost 1,900 Mi{MIC} insertion lines are in the BDSC and thousands are being balanced. References: Bellen HJ, Levis RW, He Y, Carlson JW, Evans-Holm M, Bae E, Kim J, Metaxakis A, Savakis C, Schulze KL, Hoskins RA, Spradling AC (2011) The Drosophila Gene Disruption Project: progress using transposons with distinctive site-specificities. Genetics 188:731-743. PMID: 21515576; PMCID: PMC3176542.

7

Gao G, McMahon C, Chen J, Rong YS (2008) A powerful method combining homologous recombination and site-specific recombination for targeted mutagenesis in Drosophila. Proceedings of the National Academy of Sciences USA 105:13999-14004. PMID: 18772376; PMCID: PMC2529331. Spradling AC, Bellen HJ, Hoskins RA (2011) Drosophila P elements preferentially transpose to replication origins. Proceedings of the National Academy of Sciences USA 108:15948-15953. PMID: 21896744. Venken KJT, Schulze KL, Haelterman NA, Pan H, He Y, Evans-Holm M, Carlson JW, Levis RW, Spradling AC, Hoskins RA, Bellen HJ (2011) MiMIC: a highly versatile transposon insertion resource for engineering Drosophila melanogaster genes. Nature Methods 8:737–743. PMID: 21985007; PMCID: PMC3191940. The X chromosome and 4th chromosome duplication projects (Kaufman, Hoskins, and Bellen) The goal of this proposal was to use the P[acman] technology to create a defined chromosomal duplication set for the X chromosome. Duplication mapping is an alternative to deficiency mapping, which is efficient on the autosomes but of very limited utility on the X chromosome. These defined duplications allow rescue of mutant phenotypes ascertaining that a phenotype is indeed due to a mutation in a specific gene. In addition, the rescue constructs can easily be tagged to determine where a gene is expressed and where the protein is localized. Two existing P[acman] BAC libraries, the 20 kb CHORI-322 and the 80 kb CHORI-321, were end sequenced as part of this project. The sequences were submitted to GenBank and the alignments were used to tile the clones on the genome. We end sequenced 80,000 clones so that we could essentially cover all fly genes. This work has been published (Venken et al., 2009). All the mapped clones can be searched at a web site (http://pacmanfly.org/) and ordered from BACPAC Resources (http://bacpac.chori.org/). We also created an 80 kb tiling path for the entire X chromosome euchromatin (Venken et al., 2010). Recently, a set of duplications has been created to cover about 15 gaps on the X chromosome using 150-220 kb BACs. We have similarly created an array of BACs that covers almost the entire 4th chromosome in a docking site on the third chromosome. The transgenic strains are currently being tested. References: Venken KJT, Carlson JW, Schulze KL, Pan H, He Y, Spokony R, Wan KH, Koriabine M, de Jong PJ, White KP, Bellen HJ, Hoskins RA (2009) Versatile P[acman] BAC Libraries for transgenesis studies in Drosophila melanogaster. Nature Methods 6:431-434. PMID: 19465919; PMCID: PMC2784134.

8

Venken KJ, Popodi E, Holtzman SL, Schulze KL, Park S, Carlson JW, Hoskins RA, Bellen HJ, Kaufman TC (2010) A molecularly defined duplication set for the X chromosome of Drosophila melanogaster. Genetics 186:1111-1125. PMID: 20876565; PMCID: PMC2998297. Mapping 400 EMS induced complementation groups on the X chromosome (Bellen, Rui, Kaufman) The X chromosome in Drosophila poses specific genetic challenges because of the difficulty of carrying out complementation tests with essential genes. Males can only be used for complementation testing if the corresponding mutation in an essential gene is rescued by a duplication that carries the gene on another chromosome. Hence, many fly labs have avoided screening the X chromosome for essential genes. Although the X chromosome carries approximately 2,400 genes (Adam et al., 2000), the number of essential genes has been estimated at 820 (Ashburner et al., 1999). Yet a detailed analysis of the X chromosome shows that less than 150 genes are represented by mutations established to be lethal and available from the Bloomington Drosophila Stock Center (BDSC). These mutations, combined with P element insertions that have been mapped and are homozygous lethal, still only account for less than 30% of all of the estimated essential genes on the X chromosome (Peter et al., 2002; Bellen et al., 2004; unpublished data). Hence, we estimate that lethal mutations in more than 70% of the essential genes are unavailable to the fly community after 100 years of fly genetics. The goal of this work is to more than double the collection of mutations in essential genes on the X chromosome, i.e., to bring the number of essential genes that can be immediately studied to more than 500. In addition, the point mutations in these genes will have been identified and rescued, and are thus valuable to the community. Moreover, their presence on FRT-carrying chromosomes will allow for mosaic analysis in most tissues. Hence, we will provide a collection of EMS (ethylmethane sulfonate)induced and molecularly identified mutations in ~400 different essential genes on the Drosophila X chromosome, including mutations in more than 250 essential genes that are currently not available. We will identify the molecular lesions, and document the rescue with defined 80 kb and 20 kb P[acman] duplications. We will deposit this collection of mutations with the corresponding rescuing duplications in the BDSC for distribution to the Drosophila research community. We screened 6,000 lethal mutations induced by low concentrations of EMS on an FRTcontaining X chromosome to create a “clean” collection of mutations in essential genes. Approximately 2,100 mutations cause interesting phenotypes based on two FRT mosaic screens in eye and thorax. About 1,600 mutations have already been mapped using large duplications to about ~1 Mb using 20 large X chromosome duplications. We have used gene capturing genome sequencing technologies to identify the point mutations. We have already identified mutations in about 120 complementation groups and have

9

confirmed many of them by rescuing the lethal mutations using 80 kb genomic P[acman] clones (see above). References: Adams MD, Celniker SE, Holt RA, Evans CA, Gocayne JD, et al. (2000) The genome sequence of Drosophila melanogaster. Science 287:2185-2195. PMID: 10731132. Ashburner M, Misra S, Roote J, Lewis SE, Blazej R, et al. (1999) An exploration of the sequence of a 2.9-Mb region of the genome of Drosophila melanogaster: the Adh region. Genetics. 153:179-219. PMID: 10471707; PMCID: PMC1460734. Bellen HJ, Levis RW, Liao G, He Y, Carlson JW, Tsang G, Evans-Holm M, Hiesinger PR, Schulze KL, Rubin GM, Hoskins RA, Spradling AC (2004) The BDGP gene disruption project: single transposon insertions associated with 40% of Drosophila genes. Genetics 167:761-781. PMID: 15238527; PMCID: PMC1470905. Peter A, Schöttler P, Werner M, Beinert N, Dowe G, et al. (2002) Mapping and identification of essential gene functions on the X chromosome of Drosophila. EMBO Reports 3:34-38. PMID: 11751581; PMCID: PMC1083931.

24. Harvard Drosophila RNAi Screening Center (Stephanie Mohr) DRSC Mission and Continued Funding Norbert Perrimon founded the Drosophila RNAi Screening Center (DRSC) at Harvard Medical School (www.flyrnai.org) in 2003. The DRSC mission is to provide the community with reagents and infrastructure for cell-based RNAi screening. Over the years, we have maintained this core mission and also expanded the suite of libraries and services we provide, including production of in vivo RNAi resources (see report on the Trangenic RNAi Project from L. Perkins), online availability of DRSC data sets and information, and online availability of software tools. We are pleased to announce that the DRSC was renewed for R01 grant funding by NIGMS at NIH. We look forward to continuing our mission to facilitate full-genome cell-based RNAi screens and related activities by the community. We extend our thanks to the Drosophila Board and to the entire Drosophila community for continued support of our efforts. To date, we have supported more than 125 screens and just in the past year, we have provided libraries, other reagents, consultation, etc. to more than 50 labs. DRSC activities fall mainly into the following categories (brief descriptions and past-year updates are presented below). I. DRSC Library Production & Distribution The DRSC built and maintains libraries of dsRNAs in order to support full-genome screens, smaller screens and follow-up verification. We also regularly re-annotate and 10

supplement our collection to keep current with FlyBase annotations. We also maintain plasmid reagents for over-expression screens (coverage of ~2600 protein-coding genes and >100 miRNAs). In the past year: (A) In collaboration with Dr. Mathias Beller at the Max Planck Institute for Biophysical Chemistry (Gottingen, Germany), we built a new dsRNA library with three unique reagents per gene coverage targeting the full set of Drosophila G proteincoupled receptors (GPCRs). This library is now available to the community (along with libraries targeting kinases and phosphatases; transcription factors and related proteins; transmembrane domain-containing proteins; and ubiquitin-related proteins). (B) We continued providing all of our libraries for on-site or off-site screening. Shipment of our libraries off-site, a service introduced in 2009, has gained in popularity as an increasing number of labs have access at their home institutions to equipment for high-throughput screening. As for on-site screeners, off-site screeners have access to our online data management tools and are bound by our data sharing agreement. (C) Production of custom 96-well plates of dsRNAs based on our existing genome-scale collections of templates, a service introduced in 2010, is also gaining in popularity. This has been used for example to target a set of genes indentified using another high-throughput approach, such as a proteomics study. II. On-site Screen Support We provide access to our libraries, data management tools, state-of-the-art equipment, etc. for on-site screens. We operate on a staff-assisted, researcher-driven model. In the past year: (A) We hosted a number of cultured cell screens and one primary cell screen, as well as assay development and follow-up studies, by local and visiting researchers. (B) The Perkin Elmer Evotec Opera confocal microscope remains a key instrument available to the community at our facility. We are working with Harvard Medical School to secure funds for an upgrade of the Opera computer hardware and software and assistance with the costly service contract. (C) We have added new automated instrumentation in order to further improve our ability to support assay optimization and screening. For more information on the DRSC’s efforts to further improve our support of on-site screening, please see our poster (426C). III. Online Availability of Protocols, Publications, Data and Software Tools Open online availability of protocols, publications, data and software tools relevant to RNAi screening and follow-up studies continues to be an area of focus for the DRSC. In the past year: (A) We made additional screen data sets public and created a summary page listing all public data sets. This and other new developments related to our website and database are described in our recent update in the Nucleic Acids Research database issue (Flockhart et al. 2012 PubMed ID 22067456). (B) Many researchers are interested to perform cross-species studies and integrate information learned from other species into their screen data analyses. Screeners frequently voiced

11

frustration with the need to use multiple different tools with different user interfaces in order to obtain more comprehensive ortholog prediction results. In response, we developed the DRSC Integrative Ortholog Prediction Tool (DIOPT) and the related tool DIOPT-diseases and traits (DIOPT-DIST). The resulting publication has already been named a frequently accessed paper at BMC Bioinformatics (Hu et al. 2011 PubMed ID 21880147). (C) Our informatics staff members have also expanded the DRSC database to house an increasing amount of information about Transgenic RNAi Project (TRiP) fly stocks, as well as TRiP-related validation and phenotypic data, and are developing new user interfaces for query of this information (see the TRiP report from L. Perkins). Future Directions Our primary goal is to continue supporting the community in all three areas outlined above—through full-genome and smaller library production; support of on-site and offsite screens; and availability and expansion of our database and software tools. Making small libraries is a particular focus. These provide a means for relatively rapid and highconfidence screening, and are increasingly popular in the community. These efforts leverage our existing resources well, as re-synthesis of dsRNAs based on our existing templates is 1/8th less costly than generating dsRNAs de novo. We recently applied for a small grant to support building another small library and will look for similar opportunities in the future. In addition, we plan to continue expansion of our database and website in a number of ways to support additional searches and views of DRSC and TRiP reagents and data (see the TRiP report from L. Perkins). We are also working on additional software tools to support analysis of screen results.

25. TRiP Summary for the Fly Board Meeting (Liz Perkins) The Transgenic RNAi Project (the TRiP: supported by NIGMS, R01-GM08494; N. Perrimon, PI) will enter its second round of funding beginning June 2012. The goal of the TRiP is to generate transgenic RNAi lines and make them immediately and openly available to the community through the BDSC. The TRiP facility was established at Harvard Medical School in September 2008, and the first round of funding will end (May 31, 2012) with approximately 5,200 stocks generated and 2,100 in production. All stocks are annotated on the TRiP website (http://www.flyrnai.org/TRiP-HOME.html) and on FlyBase, and transferred to the BDSC for distribution to the community. To date, over 114,000 TRiP stocks have been shipped to more than 1,250 different locations/labs in the U.S. and to 27 countries worldwide. The first-generation TRiP stocks contain long dsRNA hairpins (Ni et al, 2008; 2009). VALIUM1: 661 stocks, all are available at BDSC VALIUM10: 1,784 stocks, all are available at BDSC.

12

Almost all of these long dsRNA constructs were inserted into the 3rd chromosome at 68A4 using the phiC31 site-specific integration method (Groth et al, 2004). The strength of RNAi knockdown with VALIUM1 was not satisfactory. Higher temperature fly culturing and UAS-Dicer 2 are needed to achieve maximum knockdown. VALIUM10 was the best performing vector among our first series of related vectors, which were generated in an effort to optimize the various features of VALIUM1. The second-generation TRiP stocks contain short hairpins (shRNAs) (Ni et al, 2011). VALIUM20: 1,850 stocks, almost all available at BDSC. VALIUM22 (and the highly related vector VALIUM21): 805 V22 stocks, 95 V21 stocks, almost all available at BDSC. These constructs have been inserted into the 3rd chromosome at 68A4, and if a 2nd construct is requested for a given gene, it is inserted into the 2nd chromosome. VALIUM20, VALIUM21 and VALIUM22 have a modified scaffold derived from the microRNA miR-1 flanking the hairpin itself. Our data shows that VALIUM20 works well in the germline and is stronger than VALIUM10 in the soma. VALIUM22 (and VALIUM21) has features optimized for RNAi knockdown in the germline. Specifically, it has a P-transposase promoter instead of the hsp70 basal promoter, and a K10 3’UTR instead of the SV40 3’UTR. Data shows that VALIUM22 is stronger than VALIUM20 in the germline. Notably, by design, VALIUM21 and VALIUM22 do not work in the soma. Almost all of these stocks are available through the BDSC. Other TRiP Reagents: Through the BDSC, the TRiP also provides the community with the “TRiP Toolbox”, which includes injection stocks for labs wishing to generate their own RNAi lines and commonly used GAL4 lines with UAS-Dcr2 to enhance message knockdown. We also used the VALIUM10 backbone to generate vermillion and white versions of vectors for over-expression, i.e. pVALIUM10-roe, pVALIUM10-moe, pWALIUM20-roe and pWALIUM10-moe. With the latter vectors, researchers have the option to sub-clone using a recombination-based approach (“roe” versions) or using a standard restriction enzyme-based approach (“moe”). The VALIUM vectors, maps and cloning protocols are also available upon request and we have arranged with the plasmid repository at the DNA Resource Core at Harvard Medical School (http://plasmid.med.harvard.edu/PLASMID/) to distribute these vectors in the future. We would be happy to place the vectors with additional repositories at community request. The Future of the TRiP: During our anticipated second funding period (starting June 2012), we will continue to expand the TRiP collection of shRNA lines to our ultimate goal of 18,000 VALIUM20 stocks and 4,000 VALIUM22 stocks. To accomplish this goal we will continue to generate lines at HMS, using GSI (Cambridge, MA) for injections. In addition, we are coordinating the production of lines by a number of outside groups, including Ruth Lehmann’s lab, as well as the National Institute of Genetics in Japan (coordinated by Drs. Shu Kondo and Ryu Ueda) and Tsinghua University in China (coordinated by Dr. Jianquan Ni). Both Dr. Kondo and Dr. Ni are former postdocs of Norbert Perrimon and so prior working relationships are facilitating the TRiP’s interactions with these Asian centers. Most important to us is that these outside labs

13

agree to utilize established TRiP nomenclature and send the lines they generate to the TRiP, where they are checked for quality and then sent to the BDSC. The RSVP (the RNAi Stock Validation and Phenotypes Project): We are performing validation experiments (qPCR and phenotype analyses) to evaluate the performance of existing and new TRiP stocks. These efforts are made possible through our TRiP renewal funding and a grant from NCRR/ORIP. These data are being incorporated into the DRSC database and we are developing a web resource, the RSVP web pages and search tools, which will be appended onto the TRiP website. On the RSVP web pages, the community will have the opportunity to search and view the RSVP’s qPCR and phenotype data, as well as to share their own experiences with individual TRiP stocks. Well-organized public availability of this information will not only help individual researchers select the best lines for experiments but also help us identify additional shRNA lines that need to be produced (i.e. replacing constructs that do not work well), learn new rules for effective hairpin design, etc. The web and database infrastructure is nearly complete. We plan to make the online resource available once we have a significant amount of qPCR and phenotype data available. Shown here is an example of the “detail page” layout, which displays full information about a TRiP line as characterized by RSVP and through community input. Please note that the text shown is for informatics testing purposes— these are not real data, information or community comments. Initial RSVP data suggest good performance of TRiP stocks The production pipeline for RSVP qPCR validation and phenotyping was pioneered in the Perrimon Lab by a postdoc, Richelle Sopko. Richelle found that, on average, 6014

80% of the TRiP stocks display knock down efficiencies of >50% (see graph below of remaining expression as detected by qPCR in 0-4 hour embryos from females that have a TRiP insertion and MTD-GAL4). We have moved RSVP efforts to a production scale and are planning to perform a large number of qPCR and phenotype assays using various Gal4 drivers in the future. More on this at our platform presentation in the Techniques & Genomics session on Saturday (abstract #134) and on our poster (865A).

26. Vienna Drosophila RNAi Center (VDRC), Vienna, Austria (Lisa Meadows) The VDRC was established in April 2007 as non-profit research infrastructure by the IMP and IMBA research institutes in Vienna, Austria. Its mandate is to maintain and distribute the transgenic RNAi stocks constructed by Dickson and Keleman groups at the IMP. In addition to the original P-element based library, a second genome-wide collection of phiC31-based transgenes was made available to the Drosophila community in April 2009. The VDRC currently has 1862 registered users world-wide and has delivered a total of almost 800,000 RNAi lines to the Drosophila community. Currently, the VDRC maintains and makes available 31,838 Drosophila lines, consisting of: • 21,065 lines in the GD RNAi collection, constructed by P element mediated transgenesis • 10,740 lines in the KK RNAi collection, constructed by phiC31 mediated transgenesis into preselected single genomic locus, VIE260b, on chromosome II. • 33 miscellaneous stocks used for the construction of both collections Additionally, the VDRC provides: • 13,848 DNA constructs used for the generation of the GD collection Available soon: collection of the enhancer-Gal4s, generated by Dickson group, to be available by the end of 2012 to the Drosophila community Collectively, the GD and KK libraries cover a total 13,264 Drosophila genes (93.1%), with GD collection covering 11,972 genes (84.6%) and KK collection covering 9502 genes (71.49%). For most of the genes, more than one independent RNAi line is available through the VDRC. The VDRC is staffed with 17.5 employees: 0.5 1 1

VDRC head (Krystyna Keleman), starting March 1st, Lisa Meadows stock maintenance and shipping head (Reinhard Klug) software developer (Thomas Micheler)

15

0.5 14.5

administrative assistant (Virginia Salva) technicians for maintenance and shipping

Administratively, from March 1, 2011, the VDRC formally became part of the Vienna Biocenter Campus Support Facility (CSF), an infrastructure project funded jointly by the Austrian government and the city of Vienna. This administrative move does not effect any of the operating procedures of the VDRC, but provides for more secure long-term funding. Currently, 50% of the VDRC running costs is recovered from the user fees, while the other half is provided by the CSF.

27. DIS Report (Jim Thompson) The year 2011 was an important landmark for Drosophila Information Service (DIS). This year we completed the freely-accessible archive of past volumes of DIS at www.ou.edu/journals/dis. With the exception of some historical stock lists and other dated information like old directory listings that can be obtained from us by request, all past articles can now be obtained freely at this site. This was accomplished at no cost (not surprising, since we are a non-profit volunteer activity anyway). But the project’s success can be traced to the wonderful efforts of two people, Jenna Hellack and Clayton Hallman. Jenna Hellack is Associate Editor of DIS, and Clay Hallman has assisted our efforts in organizing and shipping for several years. They drew from often rare copies of early issues to create an accessible database of articles for community use. First published in 1934 and now at volume 94 (2011), DIS remains an active source for research, teaching, and technique articles relevant to our field. At 202 pages, the current DIS volume is the second largest in recent years, so it still seems to be a recognized outlet for the community. As usual, most contributions are received between mid-November and the end of December in response to the annual “Call for Papers”, a decades-old tradition. Most of the printed copies now go to subscribing libraries. Open access on our web site is provided shortly after the end of article acceptance in December of the publication year. But submissions are accepted at any time. Manuscripts and orders for a printed copy can be sent to James N. Thompson, jr., Department of Zoology, University of Oklahoma, Norman, OK 73019; [email protected].

16

28. FlyBase (Bill Gelbart) We are pleased to present our 2012 report to the Fly Board. Respectfully submitted, Bill Gelbart, Nick Brown, Thom Kaufman, Kathy Matthews, Richard Cripps & Maggie Werner-Washburne The Current FlyBase Home Page: FB2012_01: January 20th, 2012

2012 FlyBase Report – page 17

A. FlyBase Funding: Current Status and Future Plans FlyBase on our own behalf, and on behalf of the entire Drosophila research community, expresses our appreciation for the continuing support of the National Human Genome Research Institute (NHGRI) of NIH for the FlyBase project. As of now, we are about 2/3 of the way through the current 5 year funding period and have begun to plan our next 5 year competitive application to NHGRI. As we always do for these applications, we will be soliciting community input into establishing our future priorities, and we hope that the Fly Board will serve as one route for such input, particularly the regional representatives. We will soon be posting an on-line survey as another route; hopefully the survey will be on-line by the time the Fly Board meets. As one demonstration of community buy-in, it is essential that we get a large response to the survey (five years ago, we received over 1000 responses). We ask the Fly Board to fill out the survey and to encourage your lab members and your colleagues to do so as well. We will discuss some of our initial thoughts about plans for the next 5 years of FlyBase at the Board meeting. B. FlyBase Highlights from 2011 •

•

Public Releases in 2011: We met our schedule of 10 public releases per year. Each public release included updates to all section of FlyBase: in-house and community-contributed literature curation, D. melanogaster gene model annotations, large-scale datasets (especially related to modENCODE and DPiM publications) as well as new web site features such as the revisions to improve the power of our QuickSearch tool and the reorganization of the D. melanogaster GBrowse pages. A summary of our production release schedule and new feature highlights is presented in Table 1. We continuously monitor FlyBase web site usage. In the last calendar year, based on visits and page views, usage has increased by roughly 25%. Community-Contributed Literature Curation: Since October 2010, we have been sending weekly, automated emails to authors of newly published papers requesting that they skim curate their paper (i.e. indicate the key genes and data types within it) by completing a personalized Fast-Track Your Paper (FTYP) web form. At the end of 2010, we also carried out a one-off bulk emailing to authors of uncurated papers published in that year. In total, we have received 1678 community curation records since we started e-mailing (resulting in 9210 geneto-publication links) and the response rate to the weekly emails has been 40%. As suggested by our SAB, in November 2011 we began to send an automatic follow-up email (two weeks after the original one) to authors who had not responded to our first request, in order to increase our success rate. The early results of these follow-ups are encouraging: 37% of authors who were sent a reminder e-mail have responded. This raises the overall response rate to 60% since we started sending the reminder e-mail. The genes entered were highly accurate (requiring correction in only 5% of papers) and the flagging of data

2012 FlyBase Report – page 18

•

•

•

•

•

•

types has been sufficiently good to incorporate community curation into our full curation pipeline. Literature Curation by FlyBase: We have continued to focus on full genetic curation, prioritizing papers according to relevant data type flags assigned by triaging and by FTYP community contributions (see previous section). In the last year (specifically from FB2010_08 to FB2011_08) 1587 papers were fully curated for genetic and GO data. Gene Expression Curation: Within the past year, 741 papers were curated for expression pattern data, leading to the capture of 5748 expression statements for 2838 gene products; this includes data for 964 genes or reporters that had no prior expression data in FlyBase. Text-Mining in Support of Literature Curation: In collaboration with the WormBase text-mining groups, we continue to explore ways to use natural language processing approaches to facilitate literature triaging and full curation. These approaches have allowed the mark-up of Drosophila research articles in the GSA journals GENETICS and G3 (see below). Other applications within the FlyBase literature curation pipeline are being continually evaluated. Gene Model Annotation of D. melanogaster: In the past year, 3024 gene model annotations were updated through review by FlyBase curators. These include: o 364 newly created gene models o 17 gene models were no longer viewed as credible and were eliminated o 91 gene were merged or split o 1602 genes with one or more added transcripts o 621 genes with one or more deleted transcripts o 1649 genes with modifications to the structures of one or more transcripts At the transcript level, 8911 were reviewed. Of these, o 2598 new transcripts were created o 2544 transcript structures were modified o 769 transcripts were eliminated Gene Model Annotation of D. pseudoobscura: As an addition to the on-going annotation of D. melanogaster, in May 2009 FlyBase began the gene model annotation of a second species, D. pseudoobscura. Chromosome 2 of D. pseudoobscura has been entirely reviewed by FlyBase curators. The total gene model count for chromosome 2 went from 3,630 before review to 3,477 afterwards. Changes included: o 91 newly created gene models o 88 previously deprecated gene models were restored o 126 gene models were no longer viewed as credible and were eliminated o 1322 transcripts were extended to include UTRs o 282 gene models were extensively changed o 212 gene models were merged or split Incorporation of High Throughput Datasets: With the publication of several papers from the modENCODE group and one from the DPiM group in calendar year 2011, FlyBase has worked with the modENCODE data producers to bring the relevant data sets and DNA element prediction features into FlyBase. We

2012 FlyBase Report – page 19

•

•

•

have also developed new genome browser views and query systems for visualizing and interrogating these datasets in useful ways. Finally, we have begun to use a section of FlyBase called Library / Collection Reports to capture and present the relevant metadata on each of the high throughput datasets. Collaboration with GSA on Links to FlyBase in GENETICS & G3 Papers: GENETICS/G3 article mark-up: In collaboration with WormBase and the staff of the journal GENETICS, a mark-up pipeline that links genetic entities in GENETICS and G3: Genes, Genomes, Genetics journal articles to FlyBase went live in February 2011. The pipeline has marked up a total of 59 papers to date (43 for GENETICS and 16 for G3). A paper describing the pipeline has been published: Rangarajan et al. (2011) BMC Bioinformatics 12:175 (PMID: 21595960). FlyBase Diversity Action Plan (DAP): As a center-sized NHGRI project, FlyBase supports a DAP for developing a diverse workforce in STEM areas, especially the genomic sciences. The FlyBase DAP focuses on bringing talented undergraduates including underrepresented minorities into the genomic sciences through the funding of 1-2 year postbaccalaureate positions and through an annual half-semester course called Frontiers in Genomics. This program is centered at the University of New Mexico because of its very diverse undergraduate demographics and because of the devotion to these goals of two new FlyBase PIs (Maggie Werner-Washburne and Richard Cripps), as well as the commitment of the other FlyBase PIs to this program. We know that many of you have interests in such programs at your institutions and we would be delighted to discuss ways that we might work together. You may contact Maggie, Rich, Thom, Bill or the FlyBase DAP Training Director, Paul Szauter, who some of you know from his fly genetics days. FlyBase Scientific Advisory Board (SAB): As always, FlyBase relies on advice from its very active SAB in determining priorities and goals, through an annual one-day SAB meeting with the entire FlyBase team (most recently in early Oct. 2011) and on an ad hoc basis when issues arise. We especially acknowledge the hard work and dedication of our SAB Chair, Brian Oliver, whom we consult with frequently throughout the year. The list of the 2011 SAB members and their particularly relevant expertise is presented in Table 2.

C. Highlights of FlyBase Plans for 2012: •

•

Public Release Plans for 2012: In evaluating the balance between database production and development activities, we determined that ten releases per year left us with less time for development than was desirable, especially with numerous new types of data coming into FlyBase from modENCODE and other projects. In consultation with our Scientific Advisory Board, we decided to cut back to bimonthly releases during 2012. Our 2012 release schedule is included in Table 1. On-Going Literature Curation and Annotation Priorities: FlyBase will continue to capture information from the literature in similar fashion to 2011, including increased reliance on community-contributed curation and automated

2012 FlyBase Report – page 20

•

•

•

•

text mining. The heavy emphasis in gene model annotation will focus on D. melanogaster with a goal of a comprehensive review of all gene models for which modENCODE and other community data are not entirely consistent with the current models. modENCODE Data Handoff: Funding for the modENCODE project is terminating in the first quarter of 2012. It is essential that the incredibly valuable data produced by this project are preserved for use by the community, and FlyBase has been designated as one of the major inheritors of these data. Discussions of how to manage these very extensive and complex datasets in a way that ensures a long shelf-life are on-going with the modENCODE data producers and data coordination center (DCC). Migration to Reference Genome Assembly Release_6: Sue Celniker, PI of the BDGP, has told us that the final BDGP assembly of the reference sequenced strain of D. melanogaster is to be made public in the near future. Once it is made public, FlyBase will begin the task of migrating all of the genome sequence mapped features from the current Release_5 onto the improved Release_6. We expect it will be a matter of several months to do this carefully and to shift all of our genome views in FlyBase onto Release_6, which will then become the reference assembly. Migration to Release_6 of course also has major implications for modENCODE data, which up to now are all layered upon Release_5. DGRP Variation Data: Phenotyped whole genome variation data from the DGRP project (Trudy Mackay, PI) is an incredibly valuable resource for understanding variation in complex traits, and is a model for how to approach such problems in a variety of organisms, including GWAS approaches to identifying loci contributing to the heritable component of complex human diseases. FlyBase will work with the DGRP group in 2012 to determine how it can contribute to making the genomic and phenotypic variation data accessible to the community in the context of other FlyBase data. Making FlyBase More Accessible to Non-Specialists: As we all know, Drosophila has been a major driver of advances in our understanding of biological mechanisms across all metazoans. As we also know, for a substantial number of non-specialists as well as for new people entering the study of Drosophila itself, nomenclature and fly jargon can serve as activation energy barriers inhibiting a full appreciation of the richness of Drosophila data and literature. With this in mind, FlyBase will begin in earnest to develop a more accessible view of Drosophila melanogaster gene records, including humanauthored executive summaries focusing on molecular and functional information, improved orthology calls (being developed in collaboration with OrthoDB, Evgeny Zbodnov, PI), connections through orthologs to disease ontologies and incorporation of the Drosophila disease model literature. Through these connections, for example, a human geneticist would be able to query for D. melanogaster genes using a human gene symbol or a human disease term. Another important human health community for which FlyBase is particularly relevant is the community that studies insect vectors of infectious agents. We will also be developing lightweight approaches to make data from D.

2012 FlyBase Report – page 21

melanogaster, the nearest genetic model for these insects, more accessible for vectorologists.

Release Date 2012 November 02 2012 September 07 2012 July 06 2012 May 04 2012 March 02 2012 January 20 2011 November 11 2011 October 10 2011 September 02 2011 July 21 2011 June 24 2011 May 27 2011 April 22 2011 March 21 2011 February 18 2011 January 21

TABLE 1: FLYBASE RELEASE PLANS AS OF 2012 February Release ID Dmel annotation set Notable Events Scheduled Future 2012 Releases FB2012_06 Dmel Release 5.48 New FlyBase BLAST FB2012_05 Dmel Release 5.47 Migration to Dmel assembly Release_6 FB2012_04 Dmel Release 5.46 Human disease model data made public FB2012_03 Dmel Release 5.45 GBrowse 2.x implementation FB2012_02 Dmel Release 5.44 More modENCODE data in each release Actual Releases FB2012_01 Dmel Release 5.43 New QuickSearch Query System FB2011_10 Dmel Release 5.42 Major Dmel GBrowse Reorganization FB2011_09 Dmel Release 5.41 NEW: QS Beta / mE TFBS in GBrowse FB2011_08 Dmel Release 5.40 FB2011_07 Dmel Release 5.39 FB2011_06 Dmel Release 5.38 NEW: modENCODE Origin of Replication / Stranded RNA-Seq FB2011_05 Dmel Release 5.37 FB2011_04 Dmel Release 5.36 FB2011_03 Dmel Release 5.35 NEW: DPiM interaction maps/queries FB2011_02 Dmel Release 5.34 FB2011_01 Dmel Release 5.33 NEW: Chromatin domains / RPKMs

TABLE 2: The 2011 FLYBASE SCIENTIFIC ADVISORY BOARD (SAB) Role Affiliation Relevant Positions & Expertise Chair NIDDK, NIH Drosophila genomic analysis; coPI, modENCODE Transcription group Ken Burtis Vice UC-Davis Drosophila genetics & genomics; Diversity training Chair Rolf Apweiler Member EBI PI, UniProt; co-Director of EBI/Ensembl Amy Bejsovec Member Duke U. Drosophila genetics Susan Brown Member KSU PI, BeetleBase; Insect genomic analysis Susan Celniker Member LBNL Co-Director, BDGP; PI modENCODE Transcription group Michael Cherry Member Stanford U. PI, Saccharomyces Genome Database (SGD); Advisor, modENCODE Scott Edwards Member Harvard U. Vertebrate evolutionary genomics; Diversity training Janan Eppig Member Jackson Labs PI, Mouse Genome Informatics (MGI) Trudy Mackay Member NCSU Genetics/genomics of complex traits in Drosophila; PI, DGRP Paul Sternberg Member Cal Tech PI, WormBase; Advisor, modENCODE Kevin White Member U. Chicago Drosophila genomic analysis; PI, modENCODE Regulatory Element group Advisor Brian Oliver

2012 FlyBase Report – page 22