FMHS-CSCR Research Workshop 2012 23 April, 2012 (Monday, 2.15-2.40 pm)

Writing a research proposal Professor Choo Kong Bung Faculty of Medicine and Health Science Universiti Tunku Abdul Rahman Sungai Long, Kajang Selangor

Email: [email protected]; Office: K301 (3rd floor) 1

Why write research proposals? ** To obtain funds to support our research ** To review and to establish further focus(es) of ongoing research programmes ** To develop novel ideas during writing of proposal

Preparation ∗ Decide on the granting body ∗ Clarify qualification of applicants ∗ Know the application procedure, time open for application & obtain all application forms ∗ Is it a group or personal project? ∗ Collaborators: co-PIs or associate PIs??

Understand the culture of the granting body & the application procedure

Different types of research proposals e.g. Ministry of Higher Education (MoHE)

FRGS: Fundamental Research Grant Scheme ERGS: Exploratory Research Grant Scheme LRGS: Long-term Research Grant Scheme

5

Long-term research grant ** May need to first submit a concept paper ** PI and team members may be asked to present the proposal orally ** Writing up of a full proposal for further review

Principal Investigator (PI), co-Principal Investigator (co-PI) or Associate Investigator ∗ PI: should have the relevant background/experiences to supervise and execute main body of the project ∗ Co- and associate PI should have relevant expertise and experiences to complement the PI

Major issues to be addressed in a research proposal ∗ Goal ：What is our objective? ∗ Significance： ：Why is the project important? ∗ Design / approaches ：How to achieve the goal ? ∗ PI & co-PI’s： ：Who are doing which part of the study ? ∗ For multi-year project： ：When is each specific aim expected to be achieved ? ∗ Impact of project ：When the project is successfully carried out, so what ? ∗ Forecasts based on project data ：What next ?

Keys to good proposal writing ** Clear and concise (good command of language …)

** Evidence-based & logical (avoid wild speculation …)

** Relevance (avoid unnecessary information …)

Be reviewer friendly!!

Content of a successful research proposal ** Addressing interesting & worthy questions/issues ** Clear and innovative concept and rationale ** Achievable aims ** Appropriate experimental designs with feasible and up-to-date techniques ** Interesting and convincing preliminary data or relevant previous publications ** Competence and publication record of PI

Always have a rational and achievable goal!!

Preparing and writing up a research proposal

Literature Review

Observations

Questions Hypothesis Goal & aims

Writing up

Experimental design Anticipated problems /Expected results

Preparation

Preliminary Results

Hypothesis • Use relevant literature and preliminary data to build the hypothesis • Use diagrams to outline ideas and models • State the hypothesis clearly in the abstract and specific aims

A roadmap of the project ∗ Display the various steps on how the various specific aims are integrated ∗ Reveal the major experimental design and methods to be used (e.g. real-time PCR, microarray, bioinformatics, knockout mice ……..)

∗ Show timeline (milestone on completion of each specific aim over the granting period)

Overall scheme:

Specific aim 3： ：Transcriptional regulation of Zfp352 (Yrs 2-3)

An example

Upstream regulator gene(s)

Specific aim 2： Effects of Zfp352 knockdown on development (Yr 2)

Upstream regulator

siRNA k/d Effects on development ？ Zfp352 regulation ZFP352 gene

cis

Specific aim 4： ： ZFP352 interaction proteins & PTM (Yr 3)

ZFP352 associating protein(s)

ZFP352 protein PTM

？ Activation of downstream target genes C(A/T)CCC

Target gene(s)

ZFP352-binding site(s)

：

Specific aim 1 Identification of downstream target genes (Yrs 1-2)

X

Y

Z

ZFP352-regulated d/s protein(s)

Preimplantation development

Experimental/study design ** Study design is NOT Materials and Methods ** Design experiments to address the questions raised in the specific aims ** Be realistic, manageable and focussed ** Be logical in step-by-step leading to your goal

Be reviewer friendly ∗ Present information logically, concisely & clearly ∗ Make appropriate sections and subsections with concise & informative titles and subtitles under a logical numbering system ∗ Prepare a list of content with page numbers of sections and subsections ∗ The following important sections are definitely read very carefully by the reviewers, so write well: specific aims, study design approaches and integration.

Writing up the proposal

The basic structure of a research proposal (I) 1. Title 2. Abstract 3. Specific aims 4. Background/literature review & significance of project 5. Preliminary data 6. Study design and major approaches 7. Materials and methods

The basic structure of a research proposal (II) 8. Anticipated results 9. Anticipated problems & solutions 10. Literature cited 11. Biodata of PI and collaborators 12. Research environment and supports 13. Budget 14. Approval from Ethics Committees 15. Appendices

Title of a research proposal ∗ Should clearly reflect the major goal of the proposed research ∗ Concise, informative and attractive ∗ Create a title by first making a list of keywords ∗ Avoid acronyms ∗ Should be decided on when the proposal is finalised

Abstract ∗ Most important section; will be read closely by reviewers (First impression on the reviewers) ∗ Final section to be written (or prepare an early draft but finalised last …) ∗ Be concise, comprehensive and organised (beware of word limitation …)

∗ Should include all key points of whole proposal: Background, hypothesis, specific aims, study design, significance of study & anticipated results

Abstract: an example Importance

Early onset breast cancer has been the unique and major health problem in Malaysia with annual increase of …

Outstanding problems

The etiology and mechanisms of breast cancer in young women is unknown. It has been suggested that carcinogenesis in utero may account for the early-onset of this cancer …

Hypothesis

To test this hypothesis, we have used fed pregnant mice with fatty diet and found increase in incidence of mammary tumours in the new born mice …

Experimental approaches

In this proposal, we will examine the alteration of mammary gland differentiation pathway in the mammary tumours derived from the new born mice using microarray, SAGE (serial analysis of gene expression) as well real-time PCR techniques

Summary Answers

Significance

This study of alterations in mammary gland differentiation in the mammary tumour of new born mice will allow us to identify the genetic and molecular mechanisms involved in the early-onset breast cancer. This information could be useful for diagnosis/treatment of early-onset breast cancer in Malaysia …

Goals and specific aims What do we intend to achieve? • Goal(s): Overall and long-term (best to have only one major goal) • Specific aims: milestones/steps to reach the goal (no more than 3-5 specific aims) • Specific aims: Be specific, be achievable, be logical … >> Both goals and specific aims: Clear link to test of hypothesis Clear link to study design …

Specific aim: an example Approaches

Rationale and hypothesis

Specific Aim 1. To determine the role of nucleosomes in the regulation of Igk locus rearrangement. Our preliminary results showed that the V(D)J recombinase could not recognize RSS targets if they were arranged into a nucleosome structure. We propose experiments to extend these observations by 1) determining what fraction of the Jk gene segments are in the nucleosomal structure in cells undergoing rearrangement as compared with non-lymphoid cells, 2) determining if nucleosomes are phased across the Jk locus, 3)determining whether nucleosome remodeling complex can alter the accessibility of the Jk cluster in native or reconstituted chromatin. This analysis will give us insight of the mechanism of Igk gene rearrangement. Significance

Background and significance

WHY the study is important? • Describe what has or has not been reported (current status of information) • Importance of the research goals & potential benefits derived from the study • Cite relevant and up-to-date literature • Consider the pros and cons of the subject matter • Demonstrate that we are fully qualified & competent to address the stated questions • This is not writing a review; limit to 3-5 pages

Preliminary data What are the pilot studies have we done? • Describe only relevant preliminary data • Describe how the hypothesis is developed from and supported by the preliminary data • Figures & tables should include legends & footnotes (as in writing up a research paper) • Limit to 2-4 pages (including figures and tables)

Study design & experimental approaches

HOW do we plan to execute the project? ∗ Rationale of study design and major techniques to be used ∗ Variables and parameters of the major expt’l approaches ∗ Study design & methods must be feasible & integrated, and be consistent with specific aims and goal ∗ Potential pitfalls and alternative strategies when problems are encountered

Study design & experimental approaches • This section should include an integrated scheme (roadmap) of the core steps of the proposal • Describe how experiments are to be done; more importantly, also explain why • Also need to cite appropriate supporting literature • Limit to 4-6 pages

Overall scheme:

Specific aim 3： ：Transcriptional regulation of Zfp352 (Yrs 2-3)

An example

Upstream regulator gene(s)

Specific aim 2： Effects of Zfp352 knockdown on development (Yr 2)

Upstream regulator

siRNA k/d Effects on development ？ Zfp352 regulation ZFP352 gene

cis

Specific aim 4： ： ZFP352 interaction proteins & PTM (Yr 3)

ZFP352 associating protein(s)

ZFP352 protein PTM

Preimplantation development

？ Activation of downstream target genes C(A/T)CCC

Target gene(s)

ZFP352-binding site(s)

：

Specific aim 1 Identification of downstream target genes (Yrs 1-2)

X

Y

Z

ZFP352-regulated d/s protein(s)

From Choo KB

Literature cited ∗ Literature cited must be appropriate, complete and up-to-date ∗ Best to list the full title of each cited paper besides authorship and journal source ∗ Check to make sure of the correctness of cited papers ∗ Restrict to 40-60 most important papers

Biodata of PI and co-PI ∗ Use only updated biodata ∗ Include publications in the past 5 years ∗ May also include conference abstracts and monographs and books published

Research environment & support ∗ Is the research environment of the PI equipped to successfully carry out project? (Emphasis on superior research environment e.g. core facilities, animal facilities …) ∗ Other senior or experienced collaborators in own and other institutions ∗ Supports from affiliated organisation of PI and coPI’s ∗ Availability of postgraduate students

Budget ∗ Know the budget ceiling & average budget range ∗ Be reasonable; justify request of large sum … ∗ The budget may include： >Salaries (full- or part-time RA, postgraduate scheme) >Instruments and software (with limitation) >Consumbles (reagents, chemicals, plasticware …) >Others (conferences, MS handling fee, publication

costs …)

Approval from Research Ethics Committees • For use of human subjects: Internal Review Board (IRB) or Ethical Committee • For use of animals: Animals Use & Care Committee • Recombinant DNA Research Committee • Best to submit for internal committee approvals early to avoid delays in final submission

Appendices ∗ May include pdf copies of important supporting papers, accepted or submitted manuscripts ∗ Intellectual properties (IP’s) or licensing ∗ Agreement for use of expensive instruments from other institutions ∗ All other helpful supporting documents

Writing up a research proposal: summary

Completion and submission of proposal

Write up, discuss, review and rewrite

Organise ideas, literature review, study design and integration of specific aims into a roadmap Decide on funding body; familiarise with application procedure

A reminder

Absolutely NO PLAGIARISM!!! PLAGIARISM in any published writing is a MOST SERIOUS offence

Some useful websites http://www.nsf.gov/home/programs/guide.htm http://grants1.nih.gov/grants/grant_tips.htm http://www.niaid.nih.gov/ncn/grants/ http://deainfo.nci.nih.gov/extra/extdocs/gntapp.htm http://cpmcnet.columbia.edu/research/writing.htm http://www.csr.nih.gov/ http://www.grantcentral.com

Best of luck & Enjoy our research … 40