MSc in Medical Sciences – Faculty of Medical Sciences 2015/2016
Module Name:
Current Research Trends in Musculoskeletal Disease
Module Code:
MMB8002
Module Leader Name/Email:
Dr Kenny Rankin
[email protected]
Other Teaching Staff: Name
Email Address
Prof John Isaacs
[email protected]
Dr Andrew Knight
[email protected]
Dr Alice Lorenzi
[email protected]
Prof John Loughlin
[email protected]
Dr Fai Ng
[email protected]
Dr Arthur Pratt
[email protected]
Prof John Robinson
[email protected]
Prof Andrew Rowan
[email protected]
Dr David Young
[email protected]
General Introduction: Musculoskeletal biology is the study of the skeleton, joints and the associated ligaments and musculature. Musculoskeletal diseases are the biggest cause of chronic disability. The conditions include: osteoarthritis, inflammatory arthritis (rheumatoid arthritis and spondyloarthropathy), back pain, musculoskeletal injuries including sports injuries, crystal arthritis (gout and calcium pyrophosphate disease), metabolic bone disease (principally osteoporosis) and bone cancers. This module provides an overview of musculoskeletal disorders and investigates in depth the underlying cell biology and biochemistry of the principal musculoskeletal tissues: bone, cartilage and synovium, in health and disease. In particular the mechanisms of cartilage destruction and the role of innate and acquired immunity in arthritis will be described provide a framework in which to understand the current research trends in investigating disease processes and developing more accurate diagnostic tools and types of therapy, including surgery.
Aims: The module aims to inform students about the molecular and cellular mechanisms underlying musculoskeletal disorders, the experimental methods used to characterise the underlying (patho) physiology and both the current and future approaches to the treatment of musculoskeletal disease.
Outline of Syllabus: The taught component will comprise weekly 1-2 hour lecture/tutorial sessions on the following topics: 1. Cells of joint tissues and the inflammatory response 2. An introduction to the structure and function of joints 3. An overview of the clinical features of Musculoskeletal diseases 4. Cell biology of chondrocytes and cartilage biochemistry 5. Cartilage matrix turnover and its disregulation in arthritis 6. Connective tissue diseases 7. Cellular and molecular biology of bone destruction and remodelling 8. Orthopaedic surgery - clinical and research aspects 9. Genetic and epigenetic factors predisposing to arthritis 10. Acquired immune mechanisms in inflammatory arthritis 11. Experimental cellular therapies in Rheumatoid Arthritis 12. An overview of old and new therapies for arthritis
Learning Outcomes: Intended Knowledge Outcomes: By the end of this module students should be able to: •
distinguish between a range of different features of musculoskeletal disorders
•
discuss current frontiers of research into musculoskeletal diseases
•
display an understanding of the cellular and molecular basis for therapies used and under development for treating musculoskeletal diseases
•
display a detailed knowledge of the structure and cellular and matrix components of the main tissues in joints: bone, cartilage, synovium and fibrous tissue
•
describe the mechanisms of normal turnover of the extracellular matrix in joints and how homeostasis is disrupted in musculoskeletal disease
•
display insight into the role of innate and acquired immune mechanisms in arthritis
Intended Skill Outcomes: By the end of the module the students should be able to: •
critical explain the mechanisms of musculoskeletal diseases
•
discuss the experimental approaches used to study musculoskeletal diseases
•
present information on musculoskeletal disorders to an audience of their peers in clear written format
Starting Level of Module: No previous experience of musculoskeletal biology is required but some knowledge of basic immunology will be useful. The module is appropriate for all students accepted for the MRes course, regardless of background. Intercalating medical students will find little overlap with the MBBS course, as the focus of the module is to summarise research approaches to studying the cellular and molecular mechanisms underlying joint disease and not clinical medicine.
Schedule of Lectures: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.
An introduction to the structure and function of joints An overview of the clinical features of Musculoskeletal diseases Cell biology of chondrocytes and cartilage biochemistry Cartilage matrix turnover and its disregulation in arthritis Connective tissue diseases Cellular and molecular biology of bone destruction and remodelling Surgical approaches to the treatment of arthritis Genetic and epigenetic factors predisposing to arthritis An introduction to immunology and inflammatory responses Acquired immune mechanisms in inflammatory arthritis Cellular therapies in Rheumatoid Arthritis An overview of old and new therapies for arthritis
Assessment Deadlines: Assessment Details
Deadline
Written Exam (60%)
Week commencing 25th January 2016
In-course assessment: MCQ (20%)
To be announced
Essay (20%)
To be announced
Recommended Reading and Other Resources: https://rlo.ncl.ac.uk/modules/MMB8002/2015
MSc in Medical Sciences – Faculty of Medical Sciences 2015/2016
Module Name:
Experimental Medicine & Therapeutics
Module Code:
MMB8005
Module Leader Name/Email:
Dr Ruben Thanacoody
[email protected]
Other Teaching Staff: Name
Email Address
Professor David Jones
[email protected]
Professor Simon Thomas
[email protected]
Professor Patrick Chinnery
[email protected]
Dr Stephen Erhorn
[email protected]
Professor Ruth Plummer
[email protected]
Professor Paddy Stevenson
[email protected]
Dr Deborah Stocken
[email protected]
Mr Sean Scott
[email protected]
Dr A Hochberg (Roche) Dr S Slater (Roche)
General Introduction: This module describes the research required for the development of a medicine from first use in man to licensing and beyond, encompassing Phase 1-IV clinical trials. Teaching is provided in small group seminars and includes practical exercises, one of which is assessed. The module is based on a series of presentations and workshops by leading international experts from the pharmaceutical industry and academics from the University with experience of translational therapeutics. It is suitable for those who are interested in obtaining specific skills in the design or management of clinical trials involving medicines. By the end of the module the students will have acquired the skills necessary for initial involvement, with support, in research in drug development from first use in man to licensing and beyond. This includes designing a clinical trial protocol, applying for funding, obtaining ethical and R&D approvals, managing a research project, analysing clinical trial data and presenting the results both in writing and by oral presentation.
Aims: The module aims to develop the students’ knowledge and understanding of the pharmacological and toxicological principles relevant to drug discovery and development, of the key principles involved in developing a drug from first use in man to licensing and early clinical use, and of the design, conduct and regulation of clinical trials in humans.
Outline of Syllabus: The module covers the following topics, delivered through a series of lectures and formative assessments delivered through e-learning, supported by weekly interactive faceto-face seminars. •
UK Research Infrastructure, Research Networks
•
Research governance and ethics, Good clinical practice
•
Clinical phases of drug development, phase I-IV trials
•
Clinical trial design
•
Statistical analysis of data
•
Patient recruitment, data collection and management
•
Monitoring safety
•
Interpreting, presenting and publishing results of clinical trials
•
Drug licensing in the EU and USA
•
Critical appraisal and economic evaluation
•
Post-marketing surveillance
Learning Outcomes: Intended Knowledge Outcomes: By the end of the module students should be able to: • • • • •
Explain the research governance framework in the UK and the legal requirements before conducting research in man. State and distinguish the clinical phases of drug development and explain the purpose and key features of each phase Describe different trial designs and compare their strengths and weaknesses Examine and discuss the importance of blinding, randomisation, choice of control group, choice of appropriate endpoints in the design of clinical trials Debate and discuss ethical and funding considerations in clinical trials
• •
Describe the types and classification of adverse events and the legal requirements for reporting of adverse events. List the regulatory authorities involved in drug licensing in the UK, EU and US and describe the methods for obtaining marketing authorisation for a drug in the EU
Intended Skill Outcomes: By the end of the module students should be able to: •
Complete all the requisite applications to conduct a clinical trial in man, including: o ethics application o patient information sheet and consent form o clinical trial protocol o funding application
•
Analyse data from clinical research, perform simple statistical analyses and present the results
•
Critically appraise clinical trial results
Starting Level of Module: This module is suitable for anyone with a background in biological or medical sciences entering the MRes programme. Specialist knowledge in Pharmacology and/or Toxicology is not a requirement and the introductory sessions are tailored for those with less experience in these subject areas. However, some prior knowledge of Pharmacology and/or Toxicology is an advantage. The module is designed to be complementary to the ‘Drug Discovery and Development module and these two modules share some introductory sessions. Students taking both modules can get an overview of the drug development process from laboratory to licensing and can be awarded the MRes (Translational Medicine and Therapeutics). However, either module can also be taken in isolation if preferred.
Schedule of Lectures: Introduction to Translational medicine and therapeutics Introduction and course orientation Introduction to the translational medicine and therapeutics strand Drug absorption, distribution, metabolism and excretion Mechanisms of drug action Inter-individual variability in pharmacokinetics and drug effects Data interpretation exercise Practical exercises and revision session for introductory lectures Experimental medicine and therapeutics UK Research infrastructure and sources of research funding Early phase clinical trial methodology Use of appropriate comparators and endpoints Statistical considerations and study power Research governance, ethical principles and obtaining ethical approval. Good clinical practice Writing a clinical trial protocol Writing a patient information sheet
Seminar Lecture E-learning E-learning E-learning Seminar Seminar Lecture Lecture Seminar Lecture Seminar Seminar Seminar
Patient recruitment methodology Data collection and management Drug safety and reporting adverse effects Statistical analysis of clinical trials and other experimental medicine research Drafting a paper for publication Drug licensing in the EU and USA Pharmacovigilance and risk management planning Other designs for studies in experimental medicine and therapeutics
Lecture Lecture Lecture Lecture Seminar Lecture Lecture Lecture
Assessment Deadlines: Assessment Details
Deadline
Written Exam (60%)
Week commencing 25th January 2016
In-course assessment: Written Report (40%)
Noon 11th January 2016
Recommended Reading and Other Resources: Textbooks The Pharmacological Basis of Therapeutics. Goodman and Gilman(ed) 12th edition 2011 Section 1 Chapters 1-7 Clinical Trials. A Practical Guide to Design, Analysis and Reporting. 2006. Wang & Bakhai Principles and Practice of Clinical Trial Medicine. 2008 Chin & Lee.
Websites (a selection): ICH Harmonised Tripartite Guidelines E2A, E2D, E2E, E7, E8, E9, E10, E11 http://www.ich.org/products/guidelines/efficacy/article/efficacy-guidelines.html Clinical trials toolkit http://www.ct-toolkit.ac.uk/ Integrated Research Application System(IRAS) https://www.myresearchproject.org.uk/ELearning/IRAS_E_learning.htm EMA guidelines for first-in-man clinical trials http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09 /WC500002989.pdf
MSc in Medical Sciences – Faculty of Medical Sciences 2015/2016 Module Name:
Drug Discovery and Development
Module Code:
MMB8006
Module Leader Name/Email:
Dr Simon Hill
[email protected]
Other Teaching Staff: Name
Email Address
Professor David Jones
[email protected]
Professor Simon Thomas
[email protected]
Professor Paul Flecknell
[email protected]
Dr Jennifer Bonner
[email protected]
Professor Ann Daly
[email protected]
Dr Ruben Thanacoody
[email protected]
Professor Ruth Plummer
[email protected]
Dr Simon Wilkinson
[email protected]
Dr Ian Hardcastle
[email protected]
External staff (Contact via Simon Hill) Dr Matthew Sleeman
Medimmune
Dr Andy Blanchard
GSK
Dr Donna Finch
Medimmune
Dr Frank Bonner
FocusBio
Dr Nick Barton
GSK
Dr Jeremy Prodger
GSK
General Introduction: This module considers in detail the aspects of translational medicine called ‘drug discovery’ and ‘drug development’. The programme starts with a review of the important pharmacological principles required to underpin further learning (shared with Experimental medicine and therapeutics module). We continue with addressing how therapeutic concepts are developed in academia, industry or in clinical practice. We explore how molecules are created or identified and tested for potential clinical therapeutic effect and then how the molecules are optimised ahead of first-in-man testing. Throughout we emphasise the importance of clinical trial and medicine licensing regulatory authority requirements.
Learning is facilitated by on-line interactive material that learners undertake weekly in their own time. This is delivered in a bespoke virtual learning environment, is content rich and provides much of the factual knowledge required for a clear understanding of underlying principles of drug discovery and development. Deeper and more practical learning is promoted by face-to-face interactive, problem-solving small group seminars delivered by experts in the field from academia, clinical medicine and industry. The module is suitable for those who are interested in pursuing a career in basic or clinical biomedical research, translational medicine or within the pharmaceutical industry.
Aims: To develop a cohort of learners who fully understand and have practical experience of the drug discovery and development process and the necessary actions needed to take a basic science concept and translate it into a first in man study of a potential drug. To situate the learning within the research governance framework.
Outline of Syllabus: The module covers the following topics, delivered through a series of lectures and formative assessments delivered through e-learning, supported by weekly interactive faceto-face seminars. • • • • • • • • • •
Drug absorption, distribution, metabolism and elimination Mechanisms of drug action Inter-individual variability in pharmacokinetics and drug effects Targets and target validation Screening and hits Molecular biology underpinning drug discovery Optimising molecules Pre-clinical studies Toxicology Clinical Trial Authorisation / First-in-man
Learning Outcomes: Intended Knowledge Outcomes: By the end of the module students should be able to: • •
Describe the drug discovery and development process and it’s place in the research governance framework Evaluate and critically appraise the effectiveness of the drug discovery and development process and suggest reasons for the number of new drugs to market being less than expected
• • • • •
Summarise the methods used to identify and validate drug targets Discuss the screening of compounds for activity against targets Give an overview of the various stages of optimisation that a hit must go through to eventually become a clinical candidate Describe the pre-clinical assessments required for clinical trial authorisation Summarise the clinical phases of drug development.
Intended Skill Outcomes: By the end of the module students should be able to: • • •
Identify and complete the required documentation for a clinical trial authorisation Interact effectively with academic and industrial colleagues working on drug discovery and development projects Critically appraise pre-clinical data ahead of regulatory submission and suggest whether the candidate molecule should proceed to clinical studies.
Starting Level of Module: This module is suitable for anyone with a background in biological or medical sciences entering the MRes programme. Specialist knowledge in Pharmacology and/or Toxicology is not a requirement and the introductory sessions are tailored for those with less experience in these subject areas. However, some prior knowledge of Pharmacology and/or Toxicology is an advantage. The module is designed to be complementary to the ‘Experimental Medicine and Therapeutics’ module and these two modules share some introductory sessions. Students taking both modules can get an overview of the drug development process from laboratory to licensing and can be awarded the MRes (Translational Medicine and Therapeutics). However, either module can also be taken in isolation if preferred.
Schedule of Lectures: Schedule of lectures will be provided upon commencement of the module.
Assessment Deadlines: Assessment Details
Deadline
Written Examination (60%)
Week commencing 25th January 2016
In-course assessment: Written Assignment (40%)
To be confirmed
Recommended Reading and Other Resources: Websites (a selection): Nature Reviews: Drug Discovery http://www.nature.com/nrd/journal/v12/n7/index.html
Textbooks The Pharmacological Basis of Therapeutics. Goodman and Gilman (ed)12th edition 2011 Section 1 Chapters 1-7 Drug Discovery and Development, 2nd edition. Hill RG and Rang HP (eds). Churchill Livingstone
Journal Articles Swinney DC and Anthony J (2011) 'How were new medicines discovered?' Nature Reviews Drug Discovery 10, 507-519
MSc in Medical Sciences – Faculty of Medical Sciences 2015/2016
Module Name:
Cell Cycle Control & Cell Signalling in Health & Disease
Module Code:
MMB8008
Module Leader Name/Email:
Dr Jun-Yong Huang
[email protected]
Other Teaching Staff: Name
Email Address
Prof. Loranne Agius
[email protected]
Dr Catherine Arden
[email protected]
Dr Richard Daniel
[email protected]
Prof. Nick Europe-Finner
[email protected]
Prof. Brendan Kenny
[email protected]
Dr Penny Lovat
[email protected]
Prof. Jonathan Higgins
[email protected]
Dr Laura Maringele
[email protected]
Dr Fiona Oakley
[email protected]
Prof. Michael Taggart
[email protected]
Prof. Michael Whitaker
[email protected]
General Introduction: This module is designed to introduce students to cell cycle control and cell signalling in a number of different model organisms and to illustrate how activity of key components of these pathways can become subverted in a number of different diseases such as diabetes, liver fibrosis and cancer.
Aims: This module is designed to introduce students with fundamentals of cell biology in terms of the cell cycle controls in different model organisms. In addition, students will be provided both a thorough understanding of some key signalling pathways regulating a wide range of cellular responses and to describe how the activity of key components of these pathways can become subverted in a number of disease states such as diabetes, liver fibrosis and cancer.
Outline of Syllabus: This module covers three main aspects: 1. The fundamentals biology in terms of the cell cycle control in different model organisms (bacterial systems, Drosophila, Saccharomyces cerevisiae and human culture cell lines). It will cover DNA replication, meiosis and mitosis, autophagy, apoptosis and diseases, telomere and DNA damage repair and current research interests. 2. Calcium signalling and its dysfunction caused by diseases and current research interests. It will cover calcium signalling in embryo development, and smooth muscle contraction & phenotypic modulation. 3. The impact of some intracellular signalling pathways on the cytoskeleton, transcription factors and gene expression in health and disease and current research interests. It will cover the function of the following: receptors, G-proteins, coupled cAMP signalling in smooth muscle and NF-kB in regulating the transcription and immune response to infection, stress, cytokines, etc., tissue differentiation and glucose metabolism, insulin signalling and diabetes, and in addition to the impairment of cell death mechanisms in disease, it will also cover the signalling pathways related to EPEC altering the biology of differentiated epithelia encompassing.
Learning Outcomes: Intended Knowledge Outcomes: At the end of this module the students should be able to: 1. discuss the impact of the cell cycle control in different model organisms 2. demonstrate a clear understanding of the impact of calcium signalling in embryo development and muscle contraction in pregnancy including calcium signalling in early embryonic development and mammalian cells 3. discuss the impact of intracellular signalling pathways on the cytoskeleton, transcription factors and gene expression in health and disease 4. discuss cell division control in different model organisms 5. discuss the role of cell signalling in the diagnosis and therapy of cancer including impairment mechanisms of cell death 6. discus the role of cell signalling in apoptosis, autophagy and inflammation 7. discuss the role of insulin signalling and diabetes 8. demonstrate an understanding of the therapeutic role of interference in signalling pathways 9. discuss the role of the EPEC related signalling pathways in altering the biology of differentiated epithelia
Intended Skill Outcomes: By the end of the module the students should be able to: 1. interpret and understand data from the cell cycle control and cell signalling literature 2. critically appraise the current literature in a selected subject and present an essay 3. perform short oral presentations (on cell signalling in health and disease) 4. communicate ideas and information on the subject of cell signalling to an audience of their peers both orally and in writing.
Starting Level of Module: A first degree in Biochemistry or Biomedical Sciences would be useful, but is not essential for this module. In previous years, individuals with little or no previous knowledge of this subject area have satisfactorily completed the module.
Schedule of Lectures: 09 am-12 noon, 06 Oct. 2015, Dr Jun-Yong Huang 09 am-11 am, 13 Oct. 2015, Dr Laura Maringele 09 am-11 am, 20 Oct. 2015, Prof. Michael Whitaker 09 am-11 am, 27 Oct. 2015, Prof. Jonathan Higgins 08 am, 28 Oct. 2015 09-10 am, 03 Nov. 2015, Prof. Penny Lovat 10-11 am, 03 Nov. 2015, Prof. Penny Lovat 09-11 am, 10 Nov. 2015, Dr Fiona Oakley 09-11 am, 17 Nov. 2015, Dr Fiona Oakley 11-12 noon, 17 Nov. 2015, Dr Catherine Arden 09-11 am, 24 Nov. 2015, Prof. Nick Europe-Finner 09-11 am, 01 Dec. 2015, Prof. Michael Taggart 12 noon 02 Dec. 2015 09-11 am, 08 Dec. 2015, Prof. Loranne Agius 15-17 pm, 11 Dec. 2015, Dr Richard Daniel 09-11 am, 15 Dec. 2015,
Module Introduction & General cell cycle control in mitosis and meiosis Telomere, cancer and aging General calcium signalling in embryo development Signaling to chromatin Release the essay titles on module web site on Blackboard Apoptosis: regulation and laboratory detection Autophagy in health and disease Apoptosis signals in disease NF-kB in health and disease Insulin secretion in Type 2 diabetes G-protein coupled cyclic AMP signalling in smooth muscle Calcium signalling regulating vascular and visceral muscle The deadline for hand-in the Essays via the NESS Glucose Metabolism, insulin signalling and diabetes General bacterial biology How bacteria manipulate the host-cell signalling pathways to
Prof. Brendan Kenny
their benefit and cause disease
Assessment Deadlines: Assessment Details
Deadline
Written Examination (60%)
Week commencing 25th January 2016
In-course assessment: Essay (20%) Oral Presentation (20%)
Essay titles will be released on 28th Oct. 2015 via Blackboard. The deadline for hand-in the essay is on 12 noon of the 2nd Dec. 2015 via NESS. The deadline for hand-in the oral presentation PowerPoint is on 12 noon of the 8th Jan. 2016 via NESS. The presentation is on 12th Jan. 2016 from 911am.
Recommended Reading and Other Resources:
https://rlo.ncl.ac.uk/modules/MMB8008/2015
MSc in Medical Sciences – Faculty of Medical Sciences 2015/2016
Module Name:
Clinical Epidemiology
Module Code:
MMB8009
Module Leader Name/Email:
Professor Mark Pearce
[email protected]
Other Teaching Staff: Name
Email Address
Dr Colin Muirhead
[email protected]
Kay Mann
[email protected]
Professor Judith Rankin
[email protected]
Dr Richard McNally
[email protected]
Dr Jill McKay
[email protected]
General Introduction: This module aims to provide sound theoretical and practical understanding of the value, theoretical basis and practicalities of epidemiology and approaches to epidemiological research. Epidemiology concerns the investigation of distributions and causes of disease within populations. This module engages the students in thinking about the basic concepts of epidemiology and covers the basic epidemiology of cancer, children’s health and adult onset diseases, as well as how to investigate the potential impact of environmental, lifestyle and occupational exposures on the health of individuals. The emphasis of the course is on practical application – how can I set about answering a question about the health of individuals within an epidemiological framework? Throughout the course you will develop skills in critical appraisal by evaluating published research and the strengths and weaknesses of epidemiology itself. By the end of the course students will, with our help in small group tutorial work, have designed an epidemiological study of their choice and gained knowledge that will be provide a sound grounding if you undertake medical or biological research in the future. It is also useful for all students undertaking observational research projects, including epidemiology-related ones.
Aims: This module aims to provide the students with a sound theoretical and practical understanding of value, theoretical basis and practicalities of epidemiology and approaches to epidemiological research. Epidemiology concerns the investigation of distributions and causes of disease within populations. This module engages the students in thinking about the basic concepts of epidemiology and covers the basic epidemiology of cancer, children’s health and adult onset diseases, as well as how to investigate the potential impact of
environmental, lifestyle and occupational exposures on the health of individuals. The emphasis of the course is on practical application – how can I set about answering a question about the health of individuals within an epidemiological framework? Throughout the course you will develop skills in critical appraisal by evaluating published research and the strengths and weaknesses of epidemiology itself. By the end of the course students will, with our help in small group tutorial work, have designed an epidemiological study of their choice and gained knowledge that will be provide a sound grounding if you undertake medical or biological research in the future. No previous experience of epidemiology is required as the module assumes no prior knowledge of epidemiological methods. The course has (almost) no statistics or formulae. The module is appropriate for all students accepted for the MRes, regardless of background.
Outline of Syllabus: The syllabus includes: • • • • • • • • • • • • • • • • • •
Introductory lecture: What is it and what has epidemiology ever done for us? Epidemiological Study Design – ecological, cross-sectional and cohort studies Case-Control Studies Measuring disease frequency – incidence, prevalence and mortality Bias, confounding and Fallacies Creating Information for use in epidemiology studies Ethics and Legal issues Lifecourse Epidemiology Genetic Epidemiology Environmental and Occupational Epidemiology Cancer Epidemiology Molecular Epidemiology Perinatal and Paediatric Epidemiology Critical appraisal of epidemiology literature Barker hypothesis Causation and interpretation Cardiovascular Disease Epidemiology Developing hypotheses and planning studies (leading to the written assignment)
Learning Outcomes: Intended Knowledge Outcomes: By the end of this module the students should be able to: 1. discuss the basic concepts of epidemiology and especially environmental and genetic epidemiology and the fundamentals of epidemiological research 2. demonstrate an awareness of the limitations of all studies; error, bias and confounding 3. discuss the legal and ethical issues of the use of information 4. display an awareness of the role of epidemiological investigation in the study of disease
Intended Skill Outcomes: 1. By the end of the module the students should be able to: 1. critically appraise primary scientific literature 2. plan an epidemiological investigation taking into account ethical and consent issues, study design, information sources, data capture and issues of bias and confounding 3. produce an oral presentation in power point on the subject of clinical epidemiology
Starting Level of Module: No previous experience of epidemiology is required as the module assumes no prior knowledge of epidemiological methods. The course has (almost) no statistics or formulae. The module is appropriate for all students accepted for the MRes, regardless of background and is especially useful for students with research projects that include epidemiological or observational aspects of disease or behaviour causation.
Schedule of Lectures: 8th October 15th October 22nd October 29th October 5th November 12th November 19th November 26th November 3rd December 10th December 17th December 7th January 14th January
Lecture: Introduction to epidemiology Lecture: Measuring disease frequency Seminar: Measuring disease frequency Lecture: Study design 1 Seminar: Cohort studies Lecture: Case-control studies Seminar: Study design issues Lecture: Bias and confounding Seminar: Critical appraisal Seminar: Introduction to designing your own study Lecture: Cancer epidemiology Lecture: Creating information for use in epidemiology studies Lecture and Seminar: Genetic epidemiology Lecture: Lifecourse epidemiology Seminar: Designing your own study Lecture: Molecular epidemiology Lecture: Ethics and legal issues in epidemiology Lecture: Environmental & Occupational epidemiology Seminar: Designing your own study Seminar: The Barker hypothesis Oral Presentations Lecture: Paediatric & Perinatal epidemiology Seminar: Cardiovascular disease Seminar: Open session Lecture: Causality Seminar: Revision session
Assessment Deadlines: Assessment Details
Deadline
Written Examination (60%)
Week commencing 25th January 2016
In-course assessment: Written assignment (30%)
18th December 2015 noon
Oral Presentation (10%)
17th December 2015 (NESS submission deadline 16th December 2105 noon)
Recommended Reading and Other Resources: https://rlo.ncl.ac.uk/modules/MMB8009/2015
MSc in Medical Sciences – Faculty of Medical Sciences 2015/2016
Module Name:
The Biological Basis of Psychiatric Illness & its Treatment
Module Code:
MMB8010
Module Leader Name/Email:
Dr Hamish McAllister-Williams / Dr Richard McQuade
[email protected] [email protected]
Other Teaching Staff: Name
Email Address
Dr Mark Cunningham
[email protected]
Dr David Cousins
[email protected]
Dr Peter Gallagher
[email protected]
Dr Sasha Gartside
[email protected]
Dr Fiona LeBeau
[email protected]
Dr Adrian Lloyd
[email protected]
Dr Stuart Watson
[email protected]
Dr Chris Smart
[email protected]
General Introduction: This module explores a range of hypotheses related to the biological basis of psychiatric illnesses. The module is very much orientated around the challenges of studying psychiatric illnesses and their biology. The module will commence with an introduction to neuroanatomy, neurophysiology and neuroimaging jointly with other MRes neuroscience modules, as well as an introduction to psychiatric illnesses and an overview of biological theories of their pathophysiology. The module is then broken down into five sections each of which focuses on a specific area of research. Each section will include two lectures describing some of the challenges faced in the particular topic and the key findings to date. There will be three workshops held during the course. These will address the critical appraisal of scientific literature related to the subject areas being covered in the module. They will include focuses of identification of strengths and weaknesses of scientific methodology, summarising findings in the form of an abstract and considering the next research steps. The module is taught by psychologists, psychiatrists and neuroscientists who are experts in experimental approaches to understanding the biological basis of psychiatric illnesses. This module covers a very broad range of complex neuroscientific areas that can be challenging for students who do not have any background in neuroscience. However, such a background is not an entry requirement to the module. The intention is that the various topics will illustrate a variety of issues around the study of the biological basis of psychiatric illnesses including how this is undertaken using both animal and human studies and the translation between these techniques.
As a module of the Masters in Research Degree the emphasis is on exploring how hypotheses are derived and tested in the various research areas pertaining to the topic.
Aims: The module aims are to: •
provide the students with an introduction to the nature of psychiatric illness and the various biological abnormalities hypotheized to underlie it
•
introduce the students to some of the challenges of studying the biological basis of psychiatric illness
•
review some major proposed biological abnormalities in psychiatric illness
•
consider the nature and mechanism of action of physical treatments in psychiatric illnesses
•
develop critical appraisal skills of students as applied to the published literature related to the biological basis of psychiatric illnesses
Outline of Syllabus: The module consists primarily of lectures given by experts in the research areas covered. The module also includes the first four lectures/practicals in MMB8020 (not included in the syllabus below) which provide revision and background for all of the modules in the Neuroscience strand of the MRes. • • • • • •
Introduction to Psychiatric illness and major biological hypotheses Glutamate & Schizophrenia HPA axis and mood disorders Monoamines and mood disorders Cognition and bipolar disorder Psychopharmacological Treatments
Learning Outcomes: Intended Knowledge Outcomes: Upon completing this module, students should be able to: •
describe the concepts around diagnosis of psychiatric illnesses and the implications of these to the study of the underlying biology of these disorders
•
give examples of the major biological hypotheses related to the pathophysiology of psychiatric illnesses
•
discuss specific topics taught pertaining to biological aspects of psychiatric illnesses and their treatment
Intended Skill Outcomes: At the end of this module the students should be able to: •
integrate data from human and animal studies in the study of biology of psychiatric illnesses
•
apply analytical reasoning based on recently-acquired knowledge for the interpretation of related data
•
demonstrate skills in the critical appraisal of literature related to the study of the biological basis of psychiatric illness
•
demonstrate skills in summarising data from a research study
Starting Level of Module: Undergraduate background in psychology or a life science degree is required. Physical or engineering science backgrounds are suitable if basic background knowledge in life sciences can be demonstrated or readily acquired by independent study.
Schedule of Lectures: Date
Time
Lecture
Title
Lecturer
Notes
Introduction 9-10
1
6/10/15 10-11
2
Neuroanatomy (with other Neuroscience modules)
Neurophysiology I (with other Neuroscience modules)
Sernagor
TUES 9-11 Dent LTD
Sernagor
Joint with other Neuroscience Modules FRI 9-12
9/10/15
9-12
3&4
Neuro-anatomy practical (laboratory session) (with other Neuroscience modules)
Cunningham, Hurlbert & Sernagor
MED Dissecting Room Joint with other Neuroscience Modules
9-10
5
13/10/15 10-11
6
Neurophysiology II (with other Neuroscience modules)
Neuroimaging (with other Neuroscience modules)
Sernagor
TUES 9-11 Dent LTC
Firbank
Joint with other Neuroscience Modules
Smart
RIDB1.2.04
McAllister-Williams
RIDB1.2.04
Introduction to the Module
23/10/15
12-2
7&8
Psychiatric Illness – Focus on Schizophrenia and mood disorders Characteristic symptoms, epidemiology, functional impact & prognosis Biological abnormalities in psychiatric illnesses as candidates for the associated cognitive impairment •
30/10/15
12-2
9&10
6/11/15
12-1
11
Translation of findings in animals to humans
Cunningham
Baddiley Clark Sem Rm
6/11/15
1-2
12
GABA and glutamate in schizophrenia
LeBeau
Baddiley Clark Sem Rm
RIDB1.2.04
Neurotransmitter abnormalities • Neuroendocrine abnormalities • Abnormalities in neural networks Glutamate & Schizophrenia •
HPA axis and mood disorders 13/11/15
12-1
13
Modelling abnormalities in animals
Gartside
13/11/15
1-2
14
The challenges of assessing the HPA axis in human studies
Watson
RIDB1.2.04
Workshop 1: Critial appraisal and identification of pros and cons of research methodology 20/11/15
20/11/15
12-1 / 1-2
1-2 / 12-1
15
16
Paper related to glutamate and schizophrenia
Paper related to HPA axis and mood disorders
Cunningham / LeBeau
Rm 229, WRC, CAV
Gartside / Watson
NB – Group splits in two with each workshop run twice
Cognition and bipolar disorder 27/11/15
27/11/15
12-1
1-2
17
18
Is cognition a useful outcome measure?
Gallagher
Where in the brain is the abnormality?
Lloyd
Baddiley Clark Sem Rm
Psychopharmacological Treatments 4/12/15
12-1
19
Drug targets
McQuade
Baddiley Clark Sem Rm
4/12/15
1-2
20
Localising drugs and their effects on the brain
Cousins
Baddiley Clark Sem Rm
Workshop 2: Critial appraisal and writing an abstract 11/12/15
11/12/15
12-1 / 1-2
1-2 / 12-1
21
22
Paper related to cognition and bipolar disorder
Paper related to Psychopharmacological treatments
Gallagher / Lloyd
McQuade / Cousins
Rm 229, WRC, CAV NB – Group splits in two with each workshop run twice
Monoamines and mood disorders 18/12/16
12-1
23
Untangling mechanisms of action of mood stabilisers
McQuade
Baddiley Clark Sem Rm
18/12/16
1-2
24
The psychology of biological abnormalities
McAllister-Williams
Baddiley Clark Sem Rm
In-course Assessment, Feedback and Exam Preparation In-course Abstract writing
McQuade
MED.FELL. PC
In Course MCQ Exam
McAllister-Williams
MED. FELL.PC
25 & 26
Workshop 3: Critical appraisal – non-clinical next steps
McQuade / McAllister-Williams
Baddiley Clark Sem Rm
12-1
27
MCQ and abstract writing feedback
1-2
28
Exam preparation
McAllister-Williams / McQuade
Baddiley Clark Sem Rm
18/12/15
3-5
8/1/16
10-12
8/1/16
12.30-2
15/1/16 15/1/16
Assessment Deadlines: Assessment Details
Deadline
Written Examination (60%)
Week commencing 25th January 2016
In-course assessment: Abstract Writing (20%)
18th December 2015
Multiple Choice Questions [MCQ] (20%)
8th January 2016
Recommended Reading and Other Resources: For general background to the module: •
Concise Oxford Textbook of Psychiatry by Gelder, Gath, and Mayou
•
Biological Psychology by J.W. Kalat
•
Psychology: The Science of Mind and Behaviour by Richard Gross
•
Principles of Neural Science, 4th Ed. Kandell et al.
•
Cellular and Molecular Neuroscience by Byrne and Roberts.
Other texts will be recommended around the lectures. These are required reading by the students. Note that at a Master’s Degree level, self-directed reading is expected beyond recommended and required reading lists.
MSc in Medical Sciences – Faculty of Medical Sciences 2015/2016
Module Name:
Biology of Ageing
Module Code:
MMB8011
Module Leader Name/Email:
Dr Daryl Shanley
[email protected]
Other Teaching Staff: Name
Email Address
Dr Mary Herbert
[email protected]
Dr Mario Siervo
[email protected]
Prof Tom Kirkwood
[email protected]
Dr Viktor Korolchuk
[email protected]
Dr Joao Passos
[email protected]
Dr Carole Proctor
[email protected]
Dr Gabriele Saretzki
[email protected]
Dr David Young
[email protected]
Prof Thomas von Zglinicki
[email protected]
General Introduction: This module will present a broad perspective of current research in the biology of ageing by leading experts in the field, addressing both questions of why and how ageing occurs in addition to examining the plasticity in ageing observed with variation in factors such as nutrition. The process of ageing can be understood as the accumulation of unrepaired damage to molecules, cells and tissues. The module will include an introduction to the role of intrinsic and extrinsic stresses in generating molecular damage within cells, the broad principles defining the network of cellular defences against stress-induced damage, and the current understanding of the molecular and cellular mechanisms of ageing. As ageing involves multiple biochemical and cellular mechanisms affecting multiple tissues, the emphasis will be on building a thorough understanding of why adopting an integrative, systems approach is essential.
Aims: The module aims to: 1. provide a framework to understand why ageing occurs in almost all organisms and why ageing is particularly slow in humans 2. present details of the essential mechanisms of ageing as a basis to understand how organisms age 3. inform students on the role of intrinsic and extrinsic stress in ageing 4. provide a critical platform to judge the efficacy of potential interventions which include pharmacological, nutritional and physical
Outline of Syllabus: This module aims to provide an overview on current thinking on why ageing is observed in almost all organisms, what factors influence the rate of ageing and the key mechanisms of ageing. The module will include an introduction to the role of intrinsic and extrinsic stresses in generating molecular damage within cells, the broad principles defining the network of cellular defences against stress-induced damage, and the current understanding of the molecular and cellular mechanisms of ageing. As ageing involves multiple biochemical and cellular mechanisms affecting multiple tissues, the emphasis will be on building a thorough understanding of why adopting an integrative, systems approach is essential. The module aims to provide a critical platform to judge the efficacy of potential interventions which include pharmacological, nutritional and physical. The module contents include: 1. Definitions of longevity and ageing 2. Ageing and the life cycle 3. Evolutionary theories of ageing 4. Genetics of ageing and longevity 5. Stress, damage and repair 6. Mechanisms of stress 7. Mechanisms of ageing: damage to protein, lipid and DNA molecules; the associated maintenance and repair systems; and the consequences of the accumulation of unrepaired molecular damage. 8. A special focus on the maintenance of telomeres; apoptosis and cellular senescence; the role of mitochondria and oxidative stress; and stem cells 9. The insights gained from detailed study of caloric restriction
10. Age-associated changes in human organ/tissue integrity and function 11. Use of cell and animal model systems for ageing research 12. Use of computer simulation for ageing research 13. Measurement of ageing 14. Human population studies 15. Systems biology of ageing
Learning Outcomes: Intended Knowledge Outcomes: By the end of this module students should be able to: 1. discuss why ageing occurs and the role of stress in its progression 2. display a clear understanding of the key mechanisms of ageing 3. discuss the limitations of potential interventions to slow the ageing process 4. discriminate between normal ageing and disease 5. display an awareness of the current areas of research in ageing Intended Skill Outcomes: By the end of the module the students should be able to: 1. use their knowledge and critical appraisal skills to judge realistically the potential of possible interventions 2. suggest appropriate experimental procedures to address problems in biogerontology 3. give short oral presentations on the biology of ageing and stress to both lay and specialist audiences
Starting Level of Module: This module deals with the biology of ageing and is suitable for anyone with a background in biological or medical sciences entering the MRes programme.
Schedule of Lectures:
1. Course introduction (Shanley) 2. Evolution of ageing (Shanley) 3. Ageing and stress (von Zglinicki) 4. Oxidative stress (Passos) 5. Protein homeostasis (Proctor) 6. DNA damage (von Zglinicki) 7. Telomeres and telomerase (Saretzki) 8. Stem cell ageing (Saretzki) 9. Model organisms (Korolchuk) 10. Extra cellular matrix (Young) 11. Hormones (Shanley) 12. Nutrition (Siervo) 13. Reproductive ageing (Herbert) 14. Future of ageing (Kirkwood)
Assessment Deadlines: Assessment Details
Deadline
Written Examination (60%)
Week commencing 25th January 2016
In-course assessment: Written assignment (20%)
Oral Presentation (20%)
Set on the 11th November 2015 NESS submission (12 noon) on the 8th December 2015 Set on the 16th December 2015 NESS submission (12 noon) 12th January 2016 Presentation 13th January 2016
Recommended Reading and Other Resources: Essential Reading Time of our lives the science of human aging Kirkwood, T. B. L Oxford University Press, 2000 Further Reading The biology of aging, 3rd Edition Arking, Robert Oxford University Press,, 2006 The biology of aging : observations and principles, 3rd Edition Arking, Robert Oxford University Press, 2006 Handbook of the Biology of Aging Masoro, Edward J, Austad, Steven N Elsevier Science, 2010 Handbook of the biology of aging, 7th Edition Masoro, Edward J, Austad, Steven N. Academic, 2010 Aging at the molecular level Zglinicki, Thomas von Kluwer Academic Publishers, 2003 Journal Articles (2005), Special issue - Aging research comes of age in Cell Volume 120 Issue 4 Pages 435-568 (2011), Special issue - Royal Society discussion on the 'New science of aging' in Philosophical transactions. Volume 366 Issue 1561 Pages 3-119 (2007), Focus on Ageing in Nature reviews. Molecular cell biology Volume 8 Issue 9 (2010), Insight: Ageing supplement in Nature Volume 464 Issue 7288 Pages 503-542
MSc in Medical Sciences – Faculty of Medical Sciences 2015/2016
Module Name:
Genetics of Common Disease
Module Code:
MMB8014
Module Leader Name/Email:
Professor Heather Cordell
[email protected]
Other Teaching Staff: Name
Email Address
Dr Peter Donaldson
[email protected]
Dr Deborah Bevitt
[email protected]
Dr Chris Morris
[email protected]
Dr John Mansfield
[email protected]
Professor Mark Walker
[email protected]
Dr Joanna Elson
[email protected]
Professor Ann Daly
[email protected]
Professor John Loughlin
[email protected]
Dr Ian Wilson
[email protected]
General Introduction: This module aims to address a major area of current medical research and to provide students with an understanding of the strengths and weakness of both the current subject knowledge in this area and the practical approaches to it. Understanding the genetics of complex disease has been identified as a major post-genome challenge. The module aims to equip Level 7 students with the necessary skills to understand and develop research strategies to investigate the inheritance of complex diseases.
Aims: Specific aims are: •
To inform students in genetic variation and the genetics of non-Mendelian (complex) disease.
•
To introduce students to the different strategies and information input required to identify genes in complex diseases.
•
To compare the various practical approaches used to identify the genetic basis of common disease and to elucidate the role of genes in common disease.
•
To outline the relevance and utility of genetic investigations to understanding the pathogenesis of common diseases.
Outline of Syllabus: The module will cover: •
Genetic variation and the definition of complex genetic diseases in comparison to Mendelian disorders.
•
How to identify and assess the heritable component of a complex disease.
•
Selecting and applying different research strategies.
•
Linkage versus association analysis.
•
Immunogenetics and pharmacogenetics.
•
Data interpretation and use of computer packages for performing statistical genetic analysis
•
Knowledge of key examples of complex diseases, including examples such as: Crohn’s disease, Diabetes, Rheumatoid Arthritis, Alzheimer’s Disease, Infectious Diseases.
Learning Outcomes: Intended Knowledge Outcomes: By the end of this module students should be able to: 1. Discuss the basic principles and concepts of complex disease genetics as applied to a range of diseases [autoimmune, infectious (bacterial, viral, parasitic) and metabolic disease], including subject knowledge relating to immunogenetics and pharmacogenetics. 2. Describe the main research strategies and laboratory methods used in investigating the genetics of complex diseases 3. select appropriate research strategies and laboratory techniques for identifying genes in complex disease: linkage analysis (family studies, sib-pair analysis) or association analysis (TDT or case-control studies) 4. discuss and evaluate the appropriateness of these different research strategies and laboratory techniques for gene identification in complex diseases
Intended Skill Outcomes: By the end of the module the students should be able to: 1. consider and interpret data from studies of complex disease 2. critically appraise current literature especially in the area of study design 3. Analyse data from genetic studies of complex disease
Starting Level of Module: This module deals with human genetics and disease and is suitable for anyone with a background in biological or medical sciences entering the MRes programme. Specialist knowledge in genetics is NOT required – all of the background information required will be given as the module progresses. The module will, however, involve a relatively high level of mathematical/statistical thinking, and 30% of the module will involve performing computer analysis of genetic data. Therefore, students who have difficulty with mathematical/statistical concepts and/or with computer work should consider carefully (and perhaps discuss with the Module Leader) before selecting this module.
Provisional Schedule of Lectures: Lectures 1 and 2 (Heather Cordell) Lectures 3 and 4 (Heather Cordell) Lectures 5 and 6 (Ian Wilson) Lectures 7 and 8 (Heather Cordell) Lectures 9 and 10 (Jo Elson) Lecture 11 (Pete Donaldson) Computer Practical 1 (Heather Cordell) Lecture 12 (Pete Donaldson) Computer Practical 2 (Heather Cordell) Lecture 13 (Heather Cordell) Computer Practical 3 (Heather Cordell) Lecture 14 (Mark Walker) Lectures 15 and 16 (Ann Daly) Lecture 17 (John Loughlin) Lecture 18 + discussion (John Mansfield) Lecture 19 (Chris Morris) Lecture 20 (Debbie Bevitt) Revision session (Heather Cordell)
Basic concepts in genetics and inheritance; basic concepts in statistical hypothesis testing (type 1 error and power) Parametric and non-parametric linkage analysis; kinship and relatedness Classifying human genetic variation: allele frequencies, mutation and linkage disequilibrium (LD) Linkage disequilibrium (LD) and association analysis (family-based and case/control) The mitochondrial genome and disease The role of HLA and the MHC in human disease I Computer practical: linkage analysis The role of HLA and the MHC in human disease II Computer practical: association analysis Genome-wide association studies (GWAS) Computer practical: GWAS Genetic determinants of Type 2 Diabetes and MODY Pharmacogenetics I and II Genetics of Osteoarthritis Genetics of Crohns’ Disease Genetics of Alzheimer’s Disease (both Mendelian and nonMendelian) Host Genes and Infection I and II Revision
Assessment Deadlines: Assessment Details
Deadline
Written Examination (50%)
Week commencing 25th January 2016
In-course assessment: Computer Analysis Exercise (30%)
12 noon, Friday 11th December 2015
Critical Appraisal (20%)
12 noon, Friday 15th January 2016
Recommended Reading and Other Resources: The genetic basis of common diseases, 2nd Edition King, Richard A, Rotter, Jerome I, Motulsky, Arno G. Oxford University Press, 2002 Statistical genetics : gene mapping through linkage and association Neale, Benjamin M Taylor & Francis Group, 2008 Human molecular genetics, 4th Edition Strachan, T, Read, Andrew P., Strachan, T Garland Science, 2011 Identically different : why you can change your genes Spector, Tim Orion Publishing Co, 2013 Genetics and genomics in medicine Stachan T, Goodship J, Chinnery P Garland Publishing Inc, 2014
MSc in Medical Sciences – Faculty of Medical Sciences 2015/2016
Module Name:
Applied Immunobiology of Human Disease
Module Code:
MMB8015
Module Leader Name/Email:
Dr Catharien Hilkens
[email protected]
Other Teaching Staff: Name
Email Address
Prof. Simi Ali
[email protected]
Dr Andy Gennery
[email protected]
Prof. Sophie Hambleton
[email protected]
Prof. John Isaacs
[email protected]
Prof. Dave Jones
[email protected]
Prof. John Kirby
[email protected]
Dr Andy Knight
[email protected]
Dr Desa Lilic
[email protected]
Dr Kevin Marchbank
[email protected]
General Introduction: Immunology is the term used to describe the systems that protect the body from invasion or colonisation by harmful and/or foreign materials. This module will focus specifically on immunobiology as we consider the way the immune system is supported by, and normally works harmoniously within, healthy body tissues. We will also consider how and why normal regulation fails when the immune system is induced to cause the various forms of tissue damage associated with a wide range of diseases. Finally, the module will explain how our understanding of the biology of the immune response is being applied to the development of new strategies to improve the treatment of human diseases ranging from autoimmunity and allergy to cancer and infectious diseases, as well as the prevention of rejection of transplanted organs. This module is designed to be multi-disciplinary, drawing upon the specialized expertise and research strengths of academic staff from the Institute of Cellular Medicine (http://www.ncl.ac.uk/icm/). Our emphasis on research led teaching that encourages development of analytical and critical thinking aims to prepare students for research based careers. It will provide a strong platform for those students aiming to pursue research projects in cellular or molecular immunology.
Aims: The purpose of this module is to provide an up-to-date overview and introduction to selected aspects of Immunobiology. The module will comprise a series of lectures on recent developments, with an emphasis on understanding the supportive biological concepts. This module aims to address a major area of current medical research and to provide students with an understanding of the strengths and weakness of both the current subject knowledge in this area and the practical approaches to it. This module is designed to be multi-disciplinary, drawing upon the specialized expertise and research strengths of academic staff drawn from a number of schools in Faculty of Medical Sciences. It will provide a strong platform for those students aiming to pursue research projects in cellular or molecular immunology.
Outline of Syllabus: The syllabus includes the following topics: • • • • • • • • • • • • • •
Immune recognition of antigens Antigen presentation T cell responses B cell responses Immunological tolerance Regulation of immunity and tolerance by dendritic cells Apoptotic cell death as an effector component of the immune system Transplantation and graft rejection Immunodeficiency disorders Primary biliary cirrhosis Tumour Immunobiology Immunotherapy of rheumatoid arthritis Allergy and hypersensitivity Immunological defence mechanisms in infection
Learning Outcomes: Intended Knowledge Outcomes: By the end of this module students should be able to: 1. provide an in-depth explanation of the general conventions and principles of immunology; 2. discuss critically and with reference to recent literature recent developments in key selected areas of applied immunobiology; 3. with reference to specific examples, explain how specific functions and functional perturbations of the immune system have an impact on health and disease.
Intended Skill Outcomes: By the end of the module the students should be able to: 1. synthesise findings in applied immunobiology and explain these both verbally and in written format to specialist audiences; 2. identify and select original research papers that are relevant to specified topics in immunobiology.
Starting Level of Module: This module deals with immunobiology in health and in some disease situations. It is therefore suitable for anyone with a background in biological or medical sciences entering the MRes programme.
Schedule of Lectures: (Subject to change) Date
TBC
Time
Title
Lecturer
9-9.15
Introduction to the Module
Catharien Hilkens
9.15-11
Immune cells and recognition of antigen
Andy Knight
9-11
Antigen presentation and processing
Andy Knight
9-10
T cell responses
Kevin Marchbank
10-11
Generation of B cell immunity
Andy Knight
9-11
Immune tolerance
John Kirby
9-10
Dendritic cells balance immunity and tolerance
Catharien Hilkens
10-11
Dendritic cells as an immunotherapeutic tool
Catharien Hilkens
9-10
TBC
Simi Ali
10-11
Apoptotic cell death as an effector component of the immune system
Simi Ali
Location
TBC
9-11
Allergy & hypersensitivity
Desa Lilic
9-11
Immunology of infections
Sophie Hambleton
9-10
Transplantation and graft rejection
John Kirby
10-11
Primary Biliary Cirrhosis
Dave Jones
9-10
Immunodeficiency disorders
Andy Gennery
10-11
Tumour Immunology
John Kirby
9-11
Immunotherapy of rheumatoid arthritis
John Isaacs
9-9.45
MCQ exam
Assessment Deadlines: Assessment Details
Deadline
Written Examination (60%)
Week commencing 25th January 2016
In-course assessment: Essay (20%)
To be confirmed
Multiple Choice Questions [MCQ] (20%)
To be confirmed
Reading list – subject to change
Cellular and molecular immunology, 7th Edition Abbas, Abul K, Lichtman, Andrew H, Pillai, Shiv Saunders/Elsevier, 2012 Janeway's immunobiology, 8th Edition Murphy, Kenneth P, Travers, Paul, Walport, Mark, Janeway, Charles Garland Science, 2011 Immunology, 8th Edition Roitt, Ivan M, Brostoff, Jonathan, Roth, David Saunders, 2012
Journals
Journal of Experimental Medicine Electronic Journal The journal of immunology American Association of Immunologists, 2013 Electronic journal Nature immunology Electronic Journal Nature reviews. Immunology Electronic Journal Trends in immunology Elsevier Science, 2013 Electronic journal
MSc in Medical Sciences – Faculty of Medical Sciences 2015/2016
Module Name:
Sensory Systems
Module Code:
MMB8019
Module Leader Name/Email:
Dr Evelyne Sernagor
[email protected]
Other Teaching Staff: Name
Email Address
Prof Stuart Baker
[email protected]
Prof Andrew Blamire
[email protected]
Dr Patrick Degenaar
[email protected]
Dr Michael Firbank
[email protected]
Prof Tim Griffiths
[email protected]
Prof Anya Hurlbert
[email protected]
Dr Gabi Jordan
[email protected]
Dr Marcus Kaiser
[email protected]
Dr Adrian Rees
[email protected]
Prof Alex Thiele
[email protected]
Prof Geraldine Wright
[email protected]
General Introduction: Much of our current understanding of brain function comes from the study of sensory systems, especially vision and hearing. However, similar basic principles of neuronal function and brain structure, and the research methodologies that have been developed to invstigate sensory systems apply also to other neural systems. In this module, we start from these fundamental facts to construct an overall understanding of brain function, using examples based on a variety of research techniques, including: clinical investigations; basic neurophysiology, neuropharmacology and neuroanatomy; functional neuroimaging; behavioural approaches; and computational modelling. Our aims are therefore both to develop a specific, in-depth understanding of the neural mechanisms underlying our senses, and to develop a more general understanding of the functioning of single neurons, networks of neurons, and the whole brain. The module is taught by researchers with particular expertise in the topics covered, so that in each topic, basic textbook knowledge will be integrated with cutting-edge research methods and results.
Aims: The module aims are: 1. introduce the principles and practice of modern methods (primarily neurophysiology, imaging, and computational techniques) for investigating sensory systems (vision, audition and chemical senses). 2. explore sensory physiology at an advanced level from single neuron function to complex neuronal networks in the visual, auditory and olfactive systems. 3. gain an understanding of how basic experimental studies and clinical investigations reveal the neuronal mechanisms underlying function of sensory systems in health and disease. 4. acquire basic knowledge in neural implant devices to regain lost senses. 5. gain specific knowledge on: • • • • • • • • • •
neuronal signalling mechanisms cellular neurophysiology invasive and non-invasive techniques for studying the nervous system in humans and experimental animals computational approaches for interpreting neural network function gross sensory neuroanatomy (in primates and simpler animals) development of neural function and structure genetics and neuroanatomy of specific sensory disorders and their relationship to normal brain function multisensory integration functional links between sensory systems, and disorders thereof higher brain functions that build on sensory function, such as visual memory and attention, reading, music perception.
Outline of Syllabus: The module will introduce the principles and practice of modern methods (primarily neurophysiological, neuroimaging, and computational techniques) for investigating sensory systems including the visual and auditory systems, chemical senses through a series of lectures; Lecture topics will include: 1. Introduction to Sensory Systems research 2. Essential neuroanatomy 3. Essential cellular neurophysiology 4. Neuroimaging techniques 5. Retinal structure and function
6. Visual system development 7. Colour vision (retinal processing, genetic disorders, central processing) 8. Visual cortical function (modularity, cognitive aspects, visual attention) 9. Neural prosthetics for the restoration of sight 10. Chemical senses (taste, olfaction) 11. The auditory pathway 12. Auditory neurophysiology and neuropharmacology 13. Cortical basis and disorders of human auditory cognition 14. Multisensory integration 15. Computational approaches to understanding neuroanatomical networks and behaviour Practicals will include: 1. Fundamental neuroanatomy - Gross anatomy of the human brain. techniques. Comparative neuroanatomy.
Cellular staining
2. Spike train analysis – to analyse and quantify spiking activity in neural networks. Students will also prepare 10-minute PowerPoint presentations on in-depth topics related to the lectures, preferably based on one or more recent journal articles. Presentations will be assessed on content, organisation, style, and visual clarity. To help consolidate factual information learned throughout the course, students will have a multiple-choice-question exam during the last session of the module. The MCQ exam mark will contribute 20% to the final mark. Only lecture material will be covered in the MCQ exam.
Learning Outcomes: Intended Knowledge Outcomes: Upon completing this module students should be able to: 1. discuss the fundamental organisation of the visual and auditory systems in humans (and other animals in general), and will understand how basic experimental and clinical studies inform present-day understanding of the function of sensory systems 2. demonstrate a sound knowledge of basic experimental techniques in sensory systems research, including functional neuroimaging (fMRI, EEG, MEG), neurophysiology, neuropharmacology, and computational modelling 3. demonstrate a broad knowledge base of advanced topics in the functioning of the human auditory and visual systems, including: the development of sensory pathways; modularity of vision and hearing; higher-level cognitive functions such as language
processing and reading; the genetics and cortical bases of sensory and cognitive disorders Intended Skill Outcomes: At the end of this module the students should be able to: 1. critically evaluate the strengths and weaknesses of the pervasive research paradigms in this field 2. produce a short presentation in PowerPoint on sensory systems 3. acquire scientific knowledge through independent reading and deductive and inductive reasoning
Starting Level of Module: Undergraduate background in biological or biomedical sciences is required. A scientific, yet not biological background (e.g. physics, mathematics, computer science, and engineering) is suitable as well if the student has at least some minimal background knowledge in neuroscience or is prepared to fill the gap through independent study.
MMB8019: Lecture Time Table Date
Lecture
09/10/15
Neuroanatomy (joint with other Neuroscience modules)
ES
2
Neurophysiology I (joint with other Neuroscience modules)
ES
3
Practical
19/10/15
22/10/15
29/10/15
05/11/15
12/11/15
19/11/15 26/11/15
An introduction to the module
Neuroanatomy practical (joint with other Neuroscience modules)
AH
GC, MOC
4
Neurophysiology II (joint with other Neuroscience modules)
ES
5
Neuroimaging I (joint with other Neuroscience modules)
MJF
6
Retina I
ES
7
Retina II
ES
8
Neuroimaging techniques II fMRI
9
Retinal colour processing
GJ
10
Genetics of colour vision
GJ
Visual Development I and II
ES
13
Chemical Senses I
GW
14
Chemical Senses II
GW
Visual cortical function
ACH
13/10/15
15/10/15
Lecturer
1 06/10/15
08/10/15
Title
11-12
15-16
AMB
17
Visual prosthetics
PD
18
Neuroanatomical networks
MK
19
Auditory transduction
AR
20
Auditory pathways and function
AR
Room, time Dent LTD Tuesday 9-11am
Thursday 12-1pmL2.2 practical MED. Dissecting Room Friday 9am-12 Dent LTC Tuesday 9-11am
Thursday 12-2pm L2.6 Monday 1-2pm L2.2 Thursday 12-2pm Baddiley Clark Sem Rm Thursday 12-2pm Baddiley Clark Sem Rm Thursday 12-2pm L2.2 Thursday L2.6 Thursday 12-2pm L2.2 Thursday 12-2pm Baddiley Clark Sem Rm
03/12/15
10/12/15
21
Multisensory integration
AR
22
Visual attention and attentional mechanisms
AT
23-24
Oral presentations
17/12/15
07/01/16
Mechanisms and disorders of auditory cognition
25-26
14/01/16
TDG
To be determined
Spike train analysis practical
SB
In course MCQ
Thursday 12-2pm L2.6 Thursday 12-2pm L2.6 Thursday 12-3pm RIDB2.1.44 RIDB2.1.47 RIDB2.1.50 RIDB2.1.58 Thursday 12-2pm Practical Med Pool PC Thursday 12-2pm Med Pool PC
Assessment Deadlines: Assessment Details
Deadline
Written Examination (60%)
Week commencing 25th January 2016
In-course assessment: Multiple Choice Questions [MCQ] (20%)
14 January 2016
Oral presentation (20%)
17 December 2015 (+NESS submission 16 December 2015)
Recommended Reading and Other Resources:
https://rlo.ncl.ac.uk/modules/MMB8019/2015
MSc in Medical Sciences – Faculty of Medical Sciences 2015/2016 Module Name:
Scientific Basis of Neurological Disorders
Module Code:
MMB8020
Module Leader Name/Email:
Professor Bob Lightowlers
[email protected]
Other Teaching Staff: Name
Email Address
Professor Raj Kalaria
[email protected]
Dr Evelyne Sernagor
[email protected]
Dr Michael Firbank
[email protected]
Dr Grainne Gorman
[email protected]
Dr Tim Williams
[email protected]
Professor Rob Taylor
[email protected]
Dr Patrick Yu-Wai Man
[email protected]
Dr Bobby McFarland
[email protected]
Dr Martin Duddy
[email protected]
Dr Gavin Clowry
[email protected]
Dr Mark Cunningham
[email protected]
Dr Andy Trevelyan
[email protected]
Dr Amy Reeve
[email protected]
General Introduction: This module introduces the basic clinical aspects of many neurological disorders and details our present understanding of the molecular aetiology that underlies these disorders. It blends clinical lectures given by practicing clinicians and basic science lectures from researchers involved in unravelling the molecular basis of these disorders. Initially, the module introduces the students to several aspects of neurology and neurological research that are critical to be able to understand this module. This involves basic neuroanatomy, neurophysiology, neurological examination and neuroimaging, with a general practical session on neuroanatomical features. The module then focuses on several groups of disorders – stroke, movement disorders, dementias, eye disease, autoimmunity and mitochondrial disease. Clinicians working in these areas present the basic clinical aspects and research scientists explain the molecular dysfunctions that can lead to these diseases. Finally, the module leader gives a brief overview of the course with emphasis on general themes that run through all the neurological disorders that have been discussed.
Aims: The module aims are to: 1. acquaint students with the clinical presentations of some important neurological disorders 2. develop understanding of key aspects of cellular and molecular neuroscience in the context of their relevance to those disorders 3. introduce principles and practice of a range of modern methods for investigating the nervous system 4. describe the main ways in which nerve cells respond to insult and injury 5. examine the latest hypotheses to explain the symptoms and consequences of neurological disorders 6. explore possible ways in which neurological disorders might be treated in the future
Outline of Syllabus: The students will be given a brief foundation in several aspects of neurology and neurological research that are critical to their understanding of the module. This involves basic neuroanatomy, neurophysiology, neurological examination and neuroimaging. The syllabus will then direct the students through several groups of disorders in more detail – stroke, movement disorders, dementias, eye disease, autoimmunity and mitochondrial disease. Clinicians working in these areas will present the basic clinical aspects and research scientists will explain the molecular dysfunctions that can lead to these diseases. Finally, the module leader will give a brief resumé of the course with emphasis on general themes that run through our understanding of the molecular basis of the neurological disorders that have been discussed.
Learning Outcomes: Intended Knowledge Outcomes: On completion of the module students should be able to: 1. demonstrate an understanding of key aspects of the structure and function of nerve cells 2. discuss the cellular and molecular basis of neurological disorders 3. demonstrate an awareness of the latest concepts in the molecular aetiology of some disorders 4. discuss the reasons for using various techniques in the study of neurological disease
Intended Skill Outcomes: On completion of the module students should be able to: understand and evaluate relevant literature on neurological disease and also in the consideration of hypotheses proposed to explain molecular aetiology of selected neurological disorders.
Starting Level of Module: Strong knowledge of molecular and cell biology to 3rd year undergraduate level essential. Basic understanding of neurosciences.
Schedule of Lectures: Introductory lecture – * From Bedside to Bench (Kalaria) Essential neurological techniques (4 lectures + practical) * Basic neuroanatomy (Sernagor Dental School LTD) * Basic neurophysiology I (Sernagor Dental School LTD) * Neuroanatomy practical (Cunningham/Clowry, Dissecting Room) * Basic neurophysiology II (Sernagor Dental School LTC) * Neuroimaging techniques (Firbank Dental School LTC) The Eye (2 lectures) Anatomy of the eye, clinical and molecular aetiology of eye disease (2 lectures – Yu-Wai-Man) Stroke (2 lectures) An introduction to stroke and associated clinical features (Kalaria) Cell and molecular basis of stroke (Kalaria) Dementia (2 lectures) An introduction to Dementia and associated clin features (Kalaria) Molecular Aetiology of Alzheimers Disease (Lightowlers) Epilepsy (2 lectures) Molecular and cellular pathology of epilepsy (Trevelyan x2) Disorders of the mitochondrial genome (2 lectures) Molecular aetiology of mtDNA disease (Taylor) Defects of the mitochondrial genome – clinical aspects (McFarland) Movement Disorders I (2 lectures) Motor neurone disease – clinical aspects (Williams) Molecular aetiology of MND (Lightowlers)
Movement Disorders II (2 lectures) Parkinsons and Huntingtons Disease – Clin aspects (2 lectures - Gorman) Movement Disorders III (2 lectures) Molecular aetiology/genetics of Parkinsons Disease (Lightowlers) Trinucleotide repeat disorders (Lightowlers) Autoimmune diseases of the nervous system (3 lectures) Multiple sclerosis and myasthaenia gravis (Duddy x2) Molecular aetiology of MS – hypotheses (Lightowlers) Final seminar – The complexities of neurological disorders (Lightowlers) In course examination – Multiple Choice Questions (Pool cluster) Assessment Deadlines: Assessment Details
Deadline
Written Examination (60%)
w/c 25 January 2016
In-course assessment: Multiple Choice Questions [MCQ] (20%)
Tuesday 5th January 2016
Critical Evaluation (20%)
Friday 11th December 2015, 12 noon
Recommended Reading and Other Resources: https://rlo.ncl.ac.uk/modules/MMB8020/2015
MSc in Medical Sciences – Faculty of Medical Sciences 2015-2016
Module:
MMB8022 Stem Cells and Regenerative Medicine
Names of Lecturers/ Email Addresses: Module leader: Dr Annette Meeson
[email protected]
Professor Michael Whitaker
[email protected]
Professor Che Connon
[email protected]
Dr Andrew Filby
[email protected]
Professor David Jones
[email protected]
Dr Matthew Wright
[email protected]
Dr Arto Maatta
[email protected]
Professor Colin Jahoda
[email protected]
Dr Elizabeth Stoll
[email protected]
Dr Lyle Armstrong
[email protected]
Dr Gabriele Saretzki
[email protected]
Dr Andrew Knight
[email protected]
A number of guest lecturers will also contribute to the module content Dr Carla Mellough Professor Majlinda Lako Di Sion Phillips
[email protected] [email protected] [email protected]
General Introduction: A stem cell is a type of cell that has the ability to either divide for indefinite periods in culture to create more stem cells, or to give rise to specialized cells. Due to their ability to develop into different cell types, they could potentially provide an unlimited source of adult cells, such as bone, muscle, liver, or blood cells. Study of these important cell types also offers new insight into the fundamental processes of embryogenesis and homeostasis of adult tissues. There has been tremendous interest in stem cells in the recent years as part of a renewed interest in regenerative medicine i.e. the replacement of defective cells
and tissues with new cells and tissues. This offers hope of new therapies for otherwise intractable diseases. This module will draw upon very recent research in science and medicine to examine three broad areas in the field of stem cell and regenerative medicine: (1) the basic principles of stem cell science; (2). the basic biology of stem cells and (3) the role of stem cells in regenerative medicine.
Outline of Syllabus: The stem cell module will consider the following topics: • • • • • • • • • •
Origin and development of stem cells General terminology of stem cell classification Differentiation potential of stem cells Embryonic versus adult stem cells Isolation and culture of stem cells Tissue engineering Stem cell transplantation Stem cell based therapy Tolerance mechanisms and rejection Legal, political and ethical aspects of stem cells
Learning Outcomes: Intended Knowledge Outcomes: Upon completing this module students should be able to: 1. display a clear overview of different stem cell types and their origin 2. display a sound knowledge of basic experimental techniques used in stem cell research, including isolation and culture of stem cells 3. discuss the clinical uses of stem cells and related ethical and political aspects Intended Skill Outcomes: On completion of this module students should be able to: 1. discuss aspects of stem cell biology, current research in stems cells and the implications of stem cell research for medicine and society 2. critically appraise current literature on stem cell research 3. prepare a project proposal for scientific or clinical application
Starting Level of Module: The programme includes advanced study of subjects in stem cell biology and regenerative medicine, research skills and a 24-week research project. It assumes a background and understanding of basic molecular and cellular biology. The programme provides a springboard into a career that involves a working knowledge of scientific research in academia and industry and provides excellent preparation for PhD research studies.
Schedule of lectures: this will be provided as a timetable on BB Assessment: Assessment Details
Deadline
Exam (60%) One-hour exam (1 question to be answered out of 3)
To be announced
Essay (15%) Project proposal (25%)
To be announced
A reading list is available at: https://rlo.ncl.ac.uk/modules/MMB8022/2014
MSc in Medical Sciences – Faculty of Medical Sciences 2015/2016
Module Name:
Systems Biology
Module Code:
MMB8023
Module Leader Name/Email:
Dr Daryl Shanley
[email protected]
Other Teaching Staff: Name
Email Address
Dr Graham Smith
[email protected]
Dr Simon Cockell
[email protected]
Dr Conor Lawless
[email protected]
Dr Chris Redfern
[email protected]
General Introduction: This module provides an overview of systems biology with a focus on dynamic systems. The course introduces the range of experimental and computational tools and techniques that are available for investigating biological systems. The course will cover how the data generated can be stored, integrated and used to build effective predictive models. An emphasis will be placed on demonstrating that collaboration is essential for working at the systems level. The current focus of systems biology is on investigating cellular components and their interactions, however for systems biology to really deliver it is clear that it must incorporate studies that span biological levels. These ideas will be developed within the course. This module is suitable as an introduction to systems biology for students with a biological background or for advanced researchers approaching systems biology from a different discipline.
Aims: The module aims to: 1. provide a clear understanding of what distinguishes a systems biology from a traditional reductionist approach to solving problems in the life sciences 2. inform students of the importance of establishing an effective experiment - model prediction cycle 3. inform students of the experimental and computational technologies available
4. inform students of online data and model resources together with their associated standards 5. provide a critical platform to judge where and when a systems biology approach would be particularly useful
Outline of Syllabus: 1. The module includes lectures on: 1. An introduction to systems modelling and systems biology 2. Brief overview of essential biology 3. Brief overview of essential mathematics 4. Experimental techniques: ‘Omics’ and specific quantification methods at cellular and physiological levels 5. Currently available database resources and modelling tools 6. Current standards to enable data integration 7. Network and simulation modelling 8. Examples of modelling to include gene expression, biochemical networks and physiological systems 9. From molecules to organisms
Learning Outcomes: Intended Knowledge Outcomes: By the end of this module students should be able to: 1. identify questions within system of interest that can be feasibly answered 2. display an awareness of possible experiments that can be performed 3. to demonstrate knowledge of which kinds of numerical models are appropriate 4. display an understanding of how to make testable predictions 5. access various online resources in systems biology 6. adopt a systems approach to biological problems
Intended Skill Outcomes: By the end of the module the students should be able to: 1. use their knowledge and critical appraisal skills to judge realistically whether the problem is suitable for a systems level approach 2. suggest and undertake appropriate experimental procedures 3. suggest and undertake appropriate numerical procedures 4. give short oral presentations on systems biology to both lay and specialist audiences
Starting Level of Module: This module is suitable for anyone with a background in biological or medical sciences entering the MRes programme that is interested in engaging with a computational approach for understanding biological systems.
Schedule of Lectures: Lecture 1. Course introduction (Shanley) Lecture 2. Basic principles (Shanley) Lecture 3. High throughput technologies: overview (Cockell) Lecture 4. High throughput technologies: transcriptomics (Cockell) Lecture 5. High throughput technologies: proteomics (Cockell) Lecture 6. High throughput technologies: integration (Smith) Lecture 7. Data integration (Shanley) Lecture 8. Complex systems (Smith) Lecture 9. System Dynamics: introduction (Shanley) Lecture 10. Systems dynamics: laboratory (Redfern) Lecture 11. Systems dynamics: computational modelling I (Lawless) Lecture 12. Systems dynamics: computational modelling II (Shanley) Lecture 13. Systems biology in cancer research (Redfern) Lecture 14. Physiological systems biology (Shanley)
Assessment Deadlines:
Assessment Details
Deadline
Written Examination (60%)
Week commencing 25th January 2016
In-course assessment: Written exercise (20%)
Oral Presentation (20%)
Set on the 17th November 2015 Hand-in on the 7th December 2015 (12 noon) NESS Submission Set on the 15th December 2015 NESS Submission (12 noon) 11th January 2016 Presentation 12th January 2016
Recommended Reading and Other Resources: https://rlo.ncl.ac.uk/modules/MMB8023/2015
MSc in Medical Sciences – Faculty of Medical Sciences 2015/2016
Module Name:
Transplantation Sciences
Module Code:
MMB8025
Module Leader Name/Email:
Dr Xiao-nong Wang
[email protected]
Other Teaching Staff: Name
Email Address
Prof. Anne Dickinson
[email protected]
Dr Martin Howell
[email protected]
Dr Chris Ward
[email protected]
Prof. Simi Ali
[email protected]
Prof. Steve White
[email protected]
Prof. Graham H Jackson
[email protected]
Prof. John A Kirby
[email protected]
Dr Peter G Middleton
[email protected]
Dr Andrew R Gennery
[email protected]
Dr Laura Jardine
[email protected]
Prof. Francisco Figueiredo
[email protected]
Prof. Andrew Fisher
[email protected]
Prof. James Shaw
[email protected]
Dr Joseph Willet
[email protected]
Mr Dave Ryan
[email protected]
General Introduction: This module is designed to be multi-disciplinary to deal with the broad diversity of scientific principles and clinical concepts related to different forms of transplantations. The lectures are therefore delivered by a joint force of specialised medical staff from clinical transplant teams and academic staff from the Faculty of Medical Sciences. This module covers bench to bedside practice and will provide a window to expose the students to translational aspects of scientific research and clinical practice.
Aims: The module aims: 1. To provide an overview of and introduction to transplantation sciences in the context of solid organ and haematopoietic stem cell transplants 2. To provide sound understanding of the scientific basis underlying the therapeutic benefits and adverse effects of clinical transplants 3. To highlight the research areas in transplantation where applications of immunology, cell biology and novel technology are impacting on clinical outcome and patient wellbeing
Outline of Syllabus: The module covers following main areas: 1. Transplantation immunology: allo-Ag presentation/recognition, cellular and molecular factors involved in alloreactive immune responses, antibody mediated rejection, immunotolerance induction and immunosuppression. 2. HLA system and tissue typing: the genetic organization and polymorphisms of the HLA system, the protein structure of HLA antigens, non-HLA genetics, HLA in health and disease, and the impact of HLA matching on donor selection and transplant outcome. 3. Transplant therapeutic effect: haematopoietic stem cell transplant for leukaemia, lymphoma, and primary immunodeficiency, islet transplant and beta-cell replacement for type1 diabetes, corneal/limbal stem cell transplant for damaged tissue repair and identification of biomarkers of tolerance and rejection. 4. Transplant complications: The risk factors and pathogenesis, the prevention and development of novel therapies are introduced and discussed in the context of acute and chronic kidney graft rejection, non-immune injury in chronic lung allograft rejection, graft-versus-host disease in haematopoietic stem cell transplant. 5. Manipulation of haematopoietic stem cells for clinical use: the use of cryopreservation, T cell depletion, red blood cell depletion and stem cell isolation, and increasing the supply of donor lungs for transplantation.
Learning Outcomes: Intended Knowledge Outcomes: By the end of the module the students should be able to: demonstrate a systematic understanding of the scientific principles and concepts behind clinical transplants including:
•
the immunobiology of transplantation: cellular and molecular basis of allogeneic immune responses, tolerance induction, immunosuppression
•
tissue typing: the genetic and molecular basis of HLA system, non-HLA immunogenetics, histocompatibility, impact of HLA matching in choice of donor and transplant outcome
•
the clinical rationale for transplantation: graft versus tumour effect for malignant disorders and immune reconstitution in patients with immune deficiency
•
the pathology of transplantation: post-transplant complications e.g. graft-versus-host disease following haematopoietic stem cell transplant, rejection and overall injury following solid organ transplant
•
the manipulation of haematopoietic stem cells for clinical use: cryopreservation, T cell depletion, stem cell isolation
•
future advances in transplantation: novel scientific/clinical strategies aimed to maximise transplant therapeutic effects and minimise transplant complications
Intended Skill Outcomes: The students should be able to: 1. consider critically the advantages and disadvantages associated with transplantation of different organs and different clinical practices 2. discuss the concepts and uses of in vivo and in vitro monitoring and prediction methods 3. discuss the importance of major and minor histocompatability typing in the choice of donor 4. consider critically practical issues associated with practices in transplantation and the transplant laboratory (e.g. cryopreservation/T-cell depletion/stem cell isolation)
Starting Level of Module: A broad range of scientific topics will be delivered in the context of diverse clinical transplant settings. Therefore a medical background would be an advantage in understanding the clinical aspects of the module while a background in biosciences, particularly HLA system and allo-reactive immune responses, could be an advantage in understanding the scientific aspects of the module. The students are expected to have background knowledge of basic immunology and molecular biology. Medical background is beneficial but not essential. Concurrent study of the Applied Immunology module and Transplantation module could be complimentary but not a pre-requisite. The module aims to deliver all lectures in a logical order and cohesive manner; however the timetable for individual lectures may, sometimes, has to be governed by the availability of transplant specialists who has fixed clinical commitments. In addition, motivation, dedication and ability to drive self-directed study are essential for achieving the best outcome of the module study.
Schedule of Lectures: Date 05.10.15
12.10.15 19.10.15
14:00-15:00 Introduction to the module
15:00-16:00 HLA basics: genetics, structure & function North East Postgraduate Conference
16:00-17:00
Immunobiology of allograft rejection HLA in transplantation and donor selection
Prevention of allograft rejection Haematopoietic stem cell transplant - GvL
02.11.15
Haematopoietic stem cell transplant - GvHD
The role of APC in GvHD
09.11.15
Haematopoietic stem cell transplant for PID
Gene Therapy
Visit to PID Unit
16.11.15
Antibody mediated rejection
Biomarkers of tolerance and rejection
23.11.15
Reconditioning donor lungs for transplantation
Chronic lung allograft rejection
Islet transplant & beta-cell replacement Manipulation of HSC for clinical use
30.11.15
Corneal transplant & immune privilege
limbal stem cell transplant
07.12.15
Clinical organ transplant (renal, pancreas & liver)
Immunosuppression
14.12.15
HLA in health and disease
Non-HLA gene polymorphism & transplantation
21.12.15
Vacation
28.12.15
Vacation
04.01.16
Oral presentation assessment
11.01.16
Revision session
26.10.15
Assessment Deadlines: Assessment Details
Deadline
Written Examination (60%)
Week commencing 25th January 2016
In-course assessment: Essay (20%)
30.11.2015 (12 noon)
Oral Presentation (20%)
04.01.2016 NESS Submission (12 noon) 18.12.2015
Recommended Reading and Other Resources: ● Janeway’s Immunobiology, 8th Edition (2011) – Chapter 15: Responses to alloantigens & transplant rejection ● The Immune System: Peter Parham 3rd Edition (2009) – Chapters 5, 7, 8 and 15 ● Cellular and Molecular Immunology, Abbas AK et al. 7th Edition (2012) - Chapters 9 and 16 ● Graft versus Host Disease: Eds J.L.M. Ferrara et al. 3rd Edition (2004). ● HLA in health and disease, 2nd edition (2000), Ed Robert Lechler et al. – Chapter 2 (the structure of MHC and its molecular interactions) - Chapters 23 & 24 (HLA and transplantation I & II). ● EBMT Handbook: Haematopoietic stem cell transplantation, 2012 Eds J. Apperley, E. Carreras et al. This book provides relevant guidelines for clinical practice in HSCT as well as general scientific background of HSCT. http://www.ebmt.org/Contents/Resources/Library/EBMTESHhandbook/Pages/EBM T-ESH-handbook.aspx Due to the vast subject diversity, recent reviews and original research articles related to the lecture subjects listed above are highly recommended. Some examples are given below. Relevant reading materials will also be recommended during individual lectures. ● Klein J. Sato A. The HLA system. First of two parts. [Review] New England Journal of Medicine (2000) 343(10):702-9. ● Klein J. Sato A. The HLA system. Second of two parts.[Review] New England Journal of Medicine (2000) 343(11):782-6. ● Nathan J. Felix and Paul M. Allen: Specificity of T-cell alloreactivity. Nature reviews Immunology 2007; 7:942 ● Bruce Blazar et al. Advances in GVHD biology & therapy, 2012 Nat Rev Vol12:443 ● Paczesny S. et al. New perspectives on the biology of aGVHD, BMT 2010; 45:1-11 ● Flower M. et al. Comparative analysis of risk factors for acute and chronic GVHD. Blood 2011; 117:3214 ● Levine J. et al. aGVHD Biomarkers. Blood 2012; 119:3854. ● Fischer A et al. Gene therapy for primary adaptive immune deficiencies. J Allergy Clin Immunol, 2011; 127:1356 ● Veys P. Reduced Intensity Transplantation for Primary Immunodeficiency Disorders. Immunol Allergy Clin M Am 2010; 30:103 ● Gennery A et al. Transplantation of hematopoietic stem cells and long-term survival for primary immunodeficiencies in Europe: Entering a new century, do we do better? J Allergy Clin Immunol 2010; 126:602
● Szabolcs P. et al. Bone Marrow Transplantation for Primary Immunodeficiency Diseases. Pediatr Clin N Am 2010; 57:207 ● Targeting allograft injury and inflammation in the management of post-lung transplant bronchiolitis obliterans syndrome. Robertson AG, Griffin SM, Murphy DM, Pearson JP, Forrest IA, Dark JH, Corris PA, Ward C. Am J Transplant. 2009 Jun;9(6):1272-8.
MSc in Medical Sciences – Faculty of Medical Sciences 2015/2016 Module Name:
Genetic Medicine
Module Code:
MMB8030
Module Leader Name/Email:
Dr Colin Miles (CGM)
[email protected]
Other Teaching Staff: Name
Email Address
Dr John Sayer (JAS)
[email protected]
Dr David Kavanagh (DK)
[email protected]
Dr Teresinha Evangelista (TE)
[email protected]
Dr Jelena Mann (JM)
[email protected]
Dr David Bourn (DB)
[email protected]
Professor Kate Bushby (KB)
[email protected]
Dr Rita Horvath (RH)
[email protected]
Professor John Burn (JB)
[email protected]
Professor David Elliott (DE)
[email protected]
Dr Mauro Santibanez-Koref (MSK)
[email protected]
Dr Michael Jackson (MSJ)
[email protected]
Mr Jerome Evans (JE)
[email protected]
Mr Gareth Breese (GB)
[email protected]
Dr Simon Zwolinsky (SZ)
[email protected]
Dr Ciaron McAnulty (CMcA)
[email protected]
Professor Hanns Lochmuller (HL)
[email protected]
General Introduction: In all fields of medicine there are disorders that have a genetic basis and it is increasingly important that clinicians are able to interpret, understand and communicate genetic information to their patients and recognise when there are implications for the wider family. Similarly, diagnostic laboratories have to rapidly introduce new technologies and research findings to diagnostic service. This course aims to introduce students to this rapidly evolving field through a combination of lectures, practical exercises, and group learning. It covers the processing of genetic information, structural chromosomal abnormalities and genomic disorders, Mendelian inheritance including unusual features such as anticipation and imprinting, mitochondrial inheritance, cancer genetics and new genetic approaches to treating disease. It also introduces the strengths and weaknesses of
emerging high throughput approaches in clinical practice, including next generation sequencing, and the use of standard in silico representations of human genome data as research tools. This module is compulsory for students wishing to graduate with an MRes in Medical Genetics, but may also be taken as a single 20 credit component of other MRes strands (subject to timetabling). A high level of independence and initiative in reading around the subject is expected of students.
Aims: The primary aims of the module are as follows: 1. to consolidate knowledge of genetic information processing and inheritance patterns of human genetic disease 2. to introduce the wide variety of mutational mechanisms underlying disease phenotypes, and the detection mechanisms used to identify them 3. to introduce high throughput mutation detection techniques and in silico representations of human genome data 4. to introduce the dynamics of clinical consultations and develop an understanding of ethical and confidentiality issues within this setting
Outline of Syllabus: The module will consider: •
information processing within the cell
•
Epidemiology of heritable disease and patterns of inheritance using clinical examples.
•
Chromosome analysis including antenatal diagnosis.
•
Molecular diagnostic techniques including next generation DNA sequencing and mutation scanning.
•
Genome browsers and gene specific PCR assay design
•
Unusual patterns of inheritance - Imprinting, Mosaicism and Mitochondrial disorders, Unstable repeat disorders.
•
Genomic Disorders and techniques for copy number detection.
•
Cancer Genetics: Hereditary vs. sporadic cancer.
•
Clinical Consultation skills - pedigree analysis,risk calculations and clinical ethics.
•
Gene therapy: principles and future prospects.
Learning Outcomes: Intended Knowledge Outcomes: By the end of this module students should be able to: 1. Identify and differentiate between the different inheritance patterns exhibited by human genetic diseases 2. Differentiate between the different molecular mechanisms which can lead to genetic disease viz. loss of function, gain of function, unstable repeats, epigenetic mechanisms, mosaicism and mitochondrial mutations 3. Critical evaluation of the different methods used to identify disease causing mutations and specific diseases which arise by means of the different mechanisms. 4. Recognise some genetic disorders and know their main clinical features. Intended Skill Outcomes: By the end of the module the students should be able to: 1. draw pedigrees and interpret pedigree information 2. calculate genetic risk, and critically evaluate ethical issues surrounding specific clinical genetic scenarios 3. investigate gene structure and function using genome browsers and design gene specific PCR assays
Starting Level of Module: This module deals with human genetics and disease and is suitable for anyone with a background in biological or medical sciences entering the MRes programme. Specialised knowledge in human genetics is NOT required.
Schedule of Lectures: Lecture L1 L2
Date/Time/Venue 05/10/2015 10:00 Bioscience LT 05/10/2015 11:00
Lecturer CGM/DE
Title/content Introduction to DNA, RNA and proteins.
DE
Introduction to the Human Genome.
L3 L4 S1 L5 L6 Practical 1 (introduction) Practical 2 (assessed) L7 L8 L9 L10 L11 L12 L13 L14 L15 L16 L17
Bioscience LT 12/10/2015 19/10/2015 10:00 Bioscience LT 19/10/2015 11:00 Bioscience LT 26/10/2015 09:00 Bioscience LT 26/10/2015 10:00 Bioscience LT 26/10/2015 11:00 Bioscience LT 02/11/2015 09:00-12:00 BSTC.2.40 PC 09/11/2015 09:00-12:00 BSTC.2.40 PC 16/11/2015 09:00 Bioscience LT 16/11/2015 10:00 Bioscience LT 16/11/2015 11:00 Bioscience LT 23/11/2015 09:00 Bioscience LT 23/11/2015 10:00 Bioscience LT 23/11/2015 11:00 Bioscience LT 30/11/2015 09:00 Bioscience LT 30/11/2015 10:00 Bioscience LT 30/11/2015 11:00 Bioscience LT 07/12/2015 09:00 Bioscience LT 07/12/2015 10:00 Bioscience LT
DE
NO TEACHING Active and inactive DNA, promoters and enhancers, transcription factors.
DE
RNA and post transcriptional regulatory mechanisms.
JAS
Pedigree drawing, patterns of inheritance, risk.
GB
Introduction to cytogenetics.
JM
Introduction to epigenetics.
MSJ
Genome browser and search tools: introduction to 1st assessment.
MSJ
Assessment 1.
JE
Trisomy and prenatal diagnosis.
GB
Chromosomal rearrangements.
DB
Diagnostic molecular genetics.
JAS
Autosomal dominant inheritance.
KB
Neuromuscular disease and dystrophinopathies.
HL
Introduction to gene therapy.
RH
Mitochondrial genetics and disease.
TE
Unstable triplet repeats.
DK
Genomic disorders.
GB
Laboratory diagnosis of genomic disorders and copy number methods.
JB
Introduction to cancer genetics.
L18 S2
S3
07/12/2015 11:00 Bioscience LT 14/12/2015 09:00-12:00 Bioscience LT 21/12/2015 28/12/2015 04/01/2015 11/01/2016 09:00-12:00 Bioscience LT
CMcA
Sanger and next generation sequencing techniques.
MSK
Analysis of next generation sequencing data.
CGM/SZ
NO TEACHING NO TEACHING NO TEACHING Assessed presentations
Assessment Deadlines: Assessment Details
Deadline
Written Examination (60%)
Week commencing 25th January 2016
In-course assessment: Group Presentation (20%)
11/01/2016
Computer Practical (20%)
09/11/2015
Recommended Reading and Other Resources:
Genetic and Genomic Medicine. Authors: Strachan, Chinnery and Goodship Publishers: Garland Science ISBN: 0815344805 Human Molecular Genetics (4th Edition) Authors: Strachan and Read Publishers: Garland Science ISBN 0815341490 Chromosome abnormalities and Genetic Counselling Authors: McKinlay Gardner and Sutherland Publishers: Oxford University Press ISBN 0195149609 Online versions of several textbooks are available on Pubmed books http://www.ncbi.nlm.nih.gov/pubmed/(use the pull down menu to select books). These can be either searched or browsed. These are recent, but not the most up to date editions, and provide excellent background material. In particular, we recommend: 2). Genomes (http://www.ncbi.nlm.nih.gov/books/NBK21128/ ), 3). Molecular Cell Biology ( http://www.ncbi.nlm.nih.gov/books/NBK21475/) 4). Molecular Biology of the Cell (http://www.ncbi.nlm.nih.gov/books/NBK21054/).
5). GeneReviews (http://www.ncbi.nlm.nih.gov/books/NBK1116/).
MSc in Medical Sciences – Faculty of Medical Sciences 2015/2016
Module Name:
Developmental Genetics
Module Code:
MMB8031
Module Leader Name/Email:
Dr Heiko Peters
[email protected]
Other Teaching Staff: Name
Email Address
Dr Miranda Splitt
[email protected]
Dr Laura Yates
[email protected]
Prof Susan Lindsay
[email protected]
Dr Colin Miles
[email protected]
Dr Michael Jackson
[email protected]
Prof David Elliott
[email protected]
Dr Helen Arthur
[email protected]
Dr Simon Bamforth
[email protected]
Dr Helen Phillips
[email protected]
Dr Lyle Armstrong
[email protected]
Dr Janet Kerwin
[email protected]
General Introduction: Digit duplication, genetic brain defects, cleft lip, sex reversal, inherited heart anomalies and even tumour formation in young children – these are just a few examples within a broad spectrum of inherited disorders that may result from genetic defects disrupting developmental programmes in the growing embryo. Over the last decade, considerable technological progress has been made to greatly accelerate the identification of genetic alterations underlying these defects. A central challenge for future generation(s) of medical geneticists will be to translate this knowledge into the development of strategies improving both prevention and treatment of inherited birth defects. To successfully approach this challenge it will be necessary to understand how genetic programmes regulate growth and differentiation of uncommitted cell populations in the developing embryo, how gene functions instruct cells to differentiate along different and highly specific lineages, how transcription factors and signalling pathways are activated for specific periods of time and how this creates the striking variety of different patterns, shapes and functions of organs and tissues. Developmental genetics addresses these questions and investigates the molecular and cellular mechanisms by which gene defects result in disturbed embryonic development.
Focussing on mammalian development, including that of humans, this module will provide the students with an understanding of how genes regulate embryonic processes, how defective genes can interfere with normal development, and how gene activities can be modified in model systems to analyse gene functions in the context of a living organism. In addition to providing a comprehensive introduction to relevant key concepts of developmental genetics, it will cover the basic principles of pattern formation and organ development. Students will also gain an insight into the NHS-based Northern Genetics Service (NGS), who provide counselling to patients at risk for heritable diseases. Moreover, since most teaching staff within this module have active research programmes in the field of developmental genetics, many lectures include components that will give the students an understanding of how topical research questions are currently being addressed (see Research Focus in list of lectures).
Aims: The primary aims of this module are to: 1. introduce students to the genetic mechanisms controlling developmental processes, and to illustrate their importance for identifying and evaluating inherited disorders in humans. 2. provide the students with a comprehensive knowledge about the latest research technologies applied to the analysis and understanding of gene functions in the developing mammalian embryo.
Outline of Syllabus: This module will teach fundamental principles of Developmental Genetics and will explain how they impact on medically relevant research areas. The lectures will include several elements (“Research Focus”) of topical research projects currently carried out by group leaders involved in teaching on this module. Specifically, the module will consider: •
The early developmental processes that regulate the establishment of the body plan.
•
How gene activities control the formation of “patterns.”
•
The genetic control regulating the development of major organ systems.
•
Key signalling pathways in development and how these may contribute to tumour formation.
•
Human tissue-specific gene expression analysis and digital atlases.
•
Syndromes associated with disrupted functions of key developmental control genes.
•
Practical approaches to investigate gene function in vivo and their application in
medical genetics. •
The importance of developmental processes to the therapeutic potential of embryonic and somatic stem cells.
Learning Outcomes: Intended Knowledge Outcomes: At the end of the module students should be able to: 1. explain key aspects of genetic and developmental processes and describe how they converge to regulate the formation of a mammalian body 2. give examples of the molecular basis of some inherited developmental disorders 3. interpret novel research outcomes in the field of developmental genetics 4. discuss the potential and limitations of research strategies to investigate gene function during embryonic development 5. consider and integrate the importance of developmental genetics aspects for other, medically relevant research areas Intended Skill Outcomes: At the end of the module students should be able to: 1. use online tools to identify developmental malformation syndromes 2. critically appraise data from developmental genetics studies and to communicate these orally and in writing 3. evaluate the significance of scientific publications in the field of developmental genetics 4. efficiently design appropriate research strategies to investigate gene functions in mammalian and other vertebrate model organisms
Starting Level of Module: This module is suitable for anyone with a background in biological or medical sciences. Specialist knowledge in genetics or developmental biology is not required.
Schedule of Lectures: Lecture 1 Lecture 2 Lecture 3
Introduction Clinical Spectrum of Common Birth Abnormalities (Part A) Clinical Spectrum of Common Birth Abnormalities (Part B)
Miranda Split Laura Yates Susan Lindsay Janet Kerwin Susan Lindsay Janet Kerwin Heiko Peters
Lecture 11
Brain Development, Holoprosencephaly, Neural Tube Defects Research Focus & Dem onstration : 3D Atlas of Gene Expression in the Developing Human Embryo Craniofacial Development, Molecular Crosstalk in Epithelial-Mesenchymal Interactions Research Focus : Gene-Gene and Gene-Environment Interactions and the Risk for Cleft Lip and Cleft Palate Development of the Sensory Organs, Kidney Development and Sex Determination. Research Focus : 11p13 deletion syndrome and “master regulator” genes in development and disease: Pax6 and WT1. Genetic Engineering of Tissue-Specific and Inducible Gene Inactivation in Mice Research Focus : Identification of Developmental Gene Mutations that Predispose to Paediatric Brain Tumours Sperm Development and Infertility
Lecture 12
Research Focus : RNA-Binding Proteins and Regulation of
David Elliott
Lecture 4 Lecture 5 Lecture 6 Lecture 7 Lecture 8 Lecture 9 Lecture 10
Heiko Peters Colin Miles Colin Miles Heiko Peters Mike Jackson David Elliott
Lecture 14
Splicing The Link between Chromosome Segregation and Developmental Gene Regulation Body Axis Formation and Left-Right Asymmetry
Lecture 15
Genetics of Vasculature Development
Helen Arthur
Lecture 16
Heiko Peters
Lecture 17
Development of the Skeleton, Genetics of Common Skeletal Abnormalities Heart Development and Inherited Cardiac Malformations
Lecture 18
Research Focus : Roles of Transcription Factors for Aortic
Lecture 13
Lecture 19 Lecture 20
Arch Patterning Wnt Signalling and Planar Cell Polarity
Heiko Peters Heiko Peters
Simon Bamforth Simon Bamforth Helen Phillips Helen Phillips
Lecture 21
The role of the Wnt pathway during mammalian organogenesis Development and the Potential of Human Stem Cells
Lecture 22
Research Focus : Epigenetic Control of Stem Cell
Lyle Armstrong
Differentiation
Lyle Armstrong
Assessment Deadlines: Assessment Details
Deadline
Written Examination (60%)
Week commencing 25th January 2016
In-course assessment: Critique of a Research Paper (20%)
Set: 22nd October 2015 Hand in: 12 noon, 3rd December 2015
Group Presentation (20%)
Set: 26th November 2015 Hand in: 12 noon, 14th January 2016
Recommended Reading and Other Resources: https://rlo.ncl.ac.uk/modules/MMB8031/2015
MSc in Medical Sciences – Faculty of Medical Sciences 2015/2016
Module Name:
Toxicology
Module Code:
MMB8032
Module Leader Name/Email:
Professor Matthew Wright
[email protected]
Other Teaching Staff: Name
Email Address
Dr Jennifer Bonner
[email protected]
Prof Ann Daly
[email protected]
Dr Ruben Thanacoody
[email protected]
Dr Andrew Knight
[email protected]
Dr Colin Brown
[email protected]
Dr Chris Morris
[email protected]
Dr Simon Wilkinson
[email protected]
Dr Ernie Harpur
[email protected]
Dr Paul A Jowsey
[email protected]
General Introduction: This module will give the student a broad grounding in Toxicology and an introduction to toxicity testing as it is applied in the Pharmaceutical industry. The course will cover basic concepts, the movement of toxins (or drugs) around the body and metabolism. General mechanism by which toxins interact with cells at a molecular level will be covered and related to their adverse effects (e.g. cancer). The module will then cover the major targets for toxin (or drug) toxicity. The module will end with an overview of the preclinical and clinical toxicity tests required by licensing authorities and therefore performed by pharmaceutical companies to get their drugs to the clinic. Studies into the cause of occasional adverse drug reactions will also be examined.
Aims: The aims of the module are to give a broad understanding in Toxicology, from basic concepts and molecular mechanisms to a review of target organ toxicities, pre-clinical and clinical pharmaceutical toxicology testing. The module will provide a broad overview of Toxicology as it is applied in the Pharmaceutical industries.
Outline of Syllabus: The module will consider: 1. Basic concepts in Toxicology, (type of toxic response/factors affecting toxicity) 2. Toxicokinetics (ADME/toxicokinetic parameters) 3. Xenobiotic metabolism (phase I/II) 4. Molecular mechanisms (oxidative stress, genotoxicity, carcinogenicity, epigentics) 5. Necrosis 6. Apoptosis 7. Non-genotoxic carcinogenesis 8. Target organ toxicity (liver, kidney, skin, immune, neuro, lung) 9. Compound safety – pharmaceuticals – pre-clinical 10. Compound safety – pharmaceuticals – clinical trials 11. Idiosyncratic adverse drug reactions 12. Mechanism-based risk assessment
Learning Outcomes: Intended Knowledge Outcomes: At the end of the module students should be able to: •
discuss toxicokinetics and its relationship to toxic outcomes
•
describe the primary routes of metabolism of major toxic compounds and relate these routes to their toxicity in target organs
•
identify and explain the molecular mechanisms that cause toxicity
•
relate toxicokinetics, metabolism and molecular mechanisms to target organ toxicity
•
discuss the basic mechanisms of selected toxins in a range of organs
•
consider different pre-clinical and clinical tests performed in the testing of new pharmaceuticals
•
discuss potential causes of idiosyncratic adverse drug reactions
Intended Skill Outcomes: At the end of this module students should be able to: •
critically assess primary and secondary literature
•
apply toxicokinetics to toxic outcomes
•
critically evaluate the major elements of health evaluation
•
communicate toxicological data accurately and concisely using a variety of media
•
demonstrate a range of generic skills taught with specific reference to toxicology
•
Critically evaluate the pre-clinical and clinical tests performed in the testing of new pharmaceuticals
•
Critically appraise the potential causes of idiosyncratic adverse drug reactions
Starting Level of Module: This module deals with many aspects of Toxicology and is suitable for anyone with a background in biological or medical sciences entering the MRes programme.
Schedule of Lectures: All sessions will be on Thursdays WEEK 1 15:00 15:15 16:00 WEEK 2 15:00 16:00 17:00 WEEK 3 15:00 16:00 17:00 WEEK 4 15:00 16:00 WEEK 5 15:00 16:00
Welcome Toxicology, basic concepts 1 Toxicology, basic concepts 2 Toxicokinetics 1 Toxicokinetics 2 Toxicology RIP meeting Xenobiotic metabolism 1 Xenobiotic metabolism 2 Guidance for essay Cell death Reactive oxygen species Genotoxicity Genotoxicity and carcinogenesis
WEEK 6 15:00 16:00 WEEK 7 15:00 16:00 WEEK 8 15:00 16:00 WEEK 9 12:00 15:00 16:00 WEEK 10 15:00 16:00 WEEK 11 15:00 16:00 WEEK 12 15:00 16:00
Liver toxicity Cardiotoxicity Renal Toxicity Toxicology RIP meeting Skin toxicity Immune-mediated toxicity Hand in assignment 1 Neurotoxicity Guidance on PowerPoint presentation Assignment. Lung toxicity Idiosyncratic adverse drug reactions Safety evaluation of pharmaceuticals 1 Safety evaluation of pharmaceuticals 2 Pharmaceutical safety evaluation (50% of class) Pharmaceutical safety evaluation (50% of class)
XMAS break WEEK 13 12:00 15:00-17:00
PowerPoint presentations - submit PRESENTATIONS to staff
Assessment Deadlines: Assessment Details
Deadline
Written Examination (60%)
Week commencing 25th January 2016
In-course assessment: Appraisal of Scientific Literature (20%)
12 noon, 3/12/2015
Oral Presentation (20%)
14/01/2016
Recommended Reading and Other Resources:
The text books recommended for the Toxicology Module are:
Introductory background reading: 1. Introduction to Toxicology. Timbrell J.A. Taylor and Francis 2002 ISBN 0415247632 Essential reading 2. Casarett & Doull's Toxicology: The Basic Science of Poisons. Edited by Klaassen, C.D. McGraw-Hill Professional ISBN 978-0071470513 3. Principles of Biochemical Toxicology. Timbrell J.A. Taylor and Francis 2000 ISBN 0-7484-0736-7 Further reading 4. General and Applied Toxicology Vol. 1-3. Editors: Bryan Ballantyne, Timothy Mans, Tore Syversen Macmillan reference ltd ISBN 0-333-698681 Journals: Toxicology research papers and reviews are published in a wide range of general and specialist medical journals. The journal Toxicology contains many good reviews on Toxicology. A list of relevant and up-to-date references will be issued to all students during the module. Websites: Newcastle University http://www.ncl.ac.uk/biomedicine/research/groups/drugtox.htm http://www.ncl.ac.uk/mtc/
External http://www.thebts.org/ http://www.bps.ac.uk/view/index.html http://www.toxicology.org/ http://drnelson.uthsc.edu/cytochromeP450.html http://www.cypalleles.ki.se/
MSc in Medical Sciences – Faculty of Medical Sciences 2015/2016
Module Name:
Mitochondrial Biology and Medicine
Module Code:
MMB8034
Module Leader Name/Email:
Professor Zosia ChrzanowskaLightowlers
[email protected]
Other Teaching Staff: Name
Email Address
Prof R Taylor
[email protected]
Prof R Lightowlers
[email protected]
Dr R Hirt
[email protected]
Dr G Hudson
[email protected]
Dr J Oliveira
International visitor
Prof D Turnbull
[email protected]
Dr L Greaves
[email protected]
Prof P Chinnery
[email protected]
Dr J Elson
[email protected]
Dr A Reeve
[email protected]
Dr R Horvath
[email protected]
Dr R McFarland
[email protected]
Prof M Herbert
[email protected]
General Introduction:
Mammalian mitochondria possess their own genome, mtDNA, which encodes 13 proteins that are all vital members of the protein complexes that couple oxidative phosphorylation (OXPHOS). Hence correct expression is essential for all obligate aerobes. Human mtDNA also encodes the 24 RNA components necessary for intramitochondrial translation. The remaining proteins required for this process and all mitochondrial homeostasis, are nuclear encoded, synthesised in the cytosol and imported into the organelle. The mitochondrial oxidative phosphorylation system is the primary source of energy produced in the form of adenosine triphosphate (ATP) in all nucleated cells. A wide range of both child and adult-onset multisystem diseases are associated with deficiencies in the OXPHOS system, affecting at least 1 in 4300 individuals. Due to the dual genetic (nuclear and mitochondrial DNA) origin of genes encoding the structural components of the OXPHOS system, mitochondrial respiratory chain disorders can be inherited as Mendelian traits, inherited maternally or may occur sporadically. The clinical presentation of mitochondrial disease is associated with a broad spectrum of organ and tissue involvement with a variable age of onset. Although the correlation between the clinical and genetic diversity of respiratory chain disorders is poor and apparent phenotype-genotype association is often not present. Aspects of all these areas will be covered n the module. Mitochondrial Biology and Medicine is an area of research strength in the Faculty of Medical Sciences and has been awarded Wellcome Trust Centre status (Wellcome Trust Centre for Mitochondrial Research).
Aims: The module will provide detailed information on aspects of basic mitochondrial biology including the origins and essential functions of mitochondria, the maintenance and expression of the mitochondrial genome, and the metabolic processes in which mitochondria play a role. The module will also provide information on disease that results from mitochondrial dysfunction. This information will be informed by current research and the current state of knowledge in the field of mitochondrial biology.
Outline of Syllabus: This module is designed to provide both a thorough understanding of human mitochondrial genetics; the maintenance, replication and segregation of the mitochondrial genome (mtDNA); mtDNA transcription and intra-organellar translation; and appreciation of the metabolic processes that mitochondria are involved in; a detailed understanding of oxidative phosphorylation (OXPHOS) and the underlying biochemistry; an understanding of the interplay and coordination of nuclear and mitochondrially encoded proteins that maintains a healthy organelle; and an appreciation of the disease states and contribution to ageing that can arise as a consequence of dysfunction in any of the above.
Learning Outcomes: Intended Knowledge Outcomes: At the end of this module students should be able to: • • • • • •
Describe and discuss the origins and essential roles played by mitochondria Explain in detail and with reference to the evidence how mtDNA is maintained, expressed, replicated, transcribed and how mechanisms control intra organellar protein synthesis and OXPHOS complex biochemistry Consider and discuss the relevance of the interplay of mitochondrial and nuclear gene products Describe and discuss the dynamics of mitochondria Discuss with reference to specific examples the concepts of disease onset and progression as a consequences of organellar dysfunction
Intended Skill Outcomes: At the end of this module students should be able to: • • •
Interpret and understand data from the mitochondrial literature Evaluate the current literature Communicate ideas and information both orally and in writing to an audience of their peers on the subject of mitochondrial biology and medicine
Starting Level of Module: Undergraduate biological sciences with a good understanding of biochemistry, genetics and molecular biology.
Schedule of Lectures: Due to variable commitments on the part of the lecturers, there may be occasions when the order of the lectures varies. Lecture 1 Lecture 2 Lectures 3 & 4 Lectures 5 & 6
Lecture 7 Lecture 8 Lecture 9 Lecture 10 Lecture 11 & 12 Lecture 13 Lecture 14 Lecture 15 & 16 Lecture 17 Lecture 18 Lecture 19 Lecture 20 Lecture 21 & 22 Lecture 23 Lecture 24 Lecture 25 Lecture 26
Introductory overview Evolutionary origins Basic mitochondrial respiration (OXPHOS/respiratory chain/ATP synthesis and biochemistry Mitochondria in cell biology – non-OXPHOS functions • Fe-S cluster formation • Apoptosis • Calcium handling • Beta oxidation • Haem synthesis • Steroid synthesis • Ubiquinone synthesis Basic mitochondrial genetics mtDNA replication mtDNA transcription, processing and maturation Mt-mRNA translation Mitochondrial physiology and dynamics Clinical aspects of mitochondrial disease in adults Clinical aspects of mitochondrial disease in children Laboratory investigation of Mitochondrial Disease – To include a lab visit to see how samples are processed Mitochondrial dysfunction and ageing mtDNA variation and common disease Mitochondrial DNA – evolution and population studies Role of mitochondria in neurogenerative disorders How investigations of patient cell lines can elucidate the molecular mechanisms of mitochondrial homeostasis Clinical management and treatment of mitochondrial disease Preventing the transmission of mtDNA disease (PND, PGD, PNT MCQ Balloon debate (in groups as assessment)
Assessment Deadlines: Assessment Details
Deadline
Written Examination (60%)
Week commencing 25th January 2016
In-course assessment: Multiple Choice Questions (MCQ) (20%)
14 January 2016
Balloon debate: Abstract (5%) and Presentation (15%)
13 January 2016 electronic submission 14 January 2016 presentation
Recommended Reading and Other Resources: https://rlo.ncl.ac.uk/modules/MMB8034/2015
MSc in Medical Sciences – Faculty of Medical Sciences 2015/2016
Module Name:
Diabetes
Module Code:
MMB8035
Module Leader Name/Email:
Professor Sally Marshall
[email protected]
Other Teaching Staff: Name
Email Address
Prof Jim Shaw
[email protected]
Prof Mark Walker
[email protected]
Dr Jill McKay
[email protected]
Prof Loranne Agius
[email protected]
Dr Catherine Arden
[email protected]
Prof Roy Taylor
[email protected]
Dr Mike Trenell
[email protected]
Dr Linda Penn
[email protected]
Dr Nicky Leech
[email protected]
Dr Jola Weaver
[email protected]
Dr Dermot Neely
[email protected]
Dr Quentin Anstee
[email protected]
Prof Rudy Bilous
[email protected]
Prof Philip Home
[email protected]
General Introduction: The module offers state of the art clinical and research knowledge and experience delivered by acknowledged national and international leaders specialising in diabetes. All aspects of diabetes, including the use of up-to-date technologies, will be discussed in lectures, seminars and practical sessions.
Aims: The module aims to provide an introduction to clinical aspects of diabetes mellitus and its complications, based on an understanding of the underlying basic metabolic control processes, and to build knowledge and understanding of diabetes care and research, including an increased awareness of the clinical research tools available for the study of the disease and its complications.
Outline of Syllabus: The taught component of the module is delivered through lectures, seminars and practical sessions. The topics covered include: the genetics of diabetes; genetic epidemiology and epigenetics; glucose and lipid metabolism in the fed and fasted state and their perturbation in diabetes; insulin signalling and metabolic regulation; biochemical mechanisms of insulin secretion; insulin resistance; assessment of beta cell function; assessment of physical activity and fitness; prevention of type 2 diabetes at the population and individual level; prediction of type 1 diabetes and treatment by immunotherapeutic intervention; transplantation and regenerative medicine approaches for diabetes; factors contributing to the development of complications in diabetes; vascular studies in diabetes; liver disease in diabetes; designing, monitoring and conducting clinical trials; magnetic resonance imaging as a research tool; the use of technology in diabetes care.
Learning Outcomes: Intended Knowledge Outcomes: By the end of this module students should be able to: • • • • • • • •
provide a broad overview of diabetes mellitus as a clinical disease; list and explain the biochemical and physiological basis of the pathophysiological and metabolic changes occurring in diabetes; give examples of genetic factors that influence the development of diabetes and discuss how the functional effects of these genetic differences may contribute to disease aetiology; explain in detail the normal physiology and metabolism relevant to diabetes; give an account of the development of potential population and individual strategies to prevent diabetes, and discuss the most recent advances in these areas; explain and evaluate critically clinical research methods used in diabetes research; identify factors important in the design of studies testing new diabetes therapies and explain their relevance; propose, with justification and explanation, the design of a diabetes clinical trial.
Intended Skill Outcomes: On completion of the module, students should be able to: • • •
critically appraise, interpret and evaluate clinical trials in diabetes assess relevant literature and place it in context of their existing knowledge present a diabetes research study
Starting Level of Module: An upper-second-class Honours degree, or international equivalent, in a science or related discipline, is preferred.
Schedule of Lectures: Wed 7 Oct 1400 h Wed 7 Oct 1500 h Wed 14 Oct 1400 h Wed 14 Oct 1500 h Wed 21 Oct 1400 h Wed 21 Oct 1500 h Wed 28 Oct 1400 h Tues 3 Nov 1300 h Wed 4 Nov 1400 h Wed 4 Nov 1500 h Wed 11 Nov 1400 h Wed 11 Nov 1500 h Wed 18 Nov 1400 h Wed 18 Nov 1500 h Wed 25 Nov 1400 h Wed 25 Nov 1500 h Wed 2 Dec 0900 – 1200 h Wed 9 Dec 1400 h Wed 9 Dec 1500 h Wed 16 Dec 1400 h Wed 16 Dec 1500 h Wed 13 January time tbc
Sally Marshall What is diabetes? – general introduction Jim Shaw Type 1 diabetes Mark Walker Genetics of diabetes Jill McKay Genetic epidemiology and epigenetics Loranne Agius Glucose and lipid metabolism in the fed state Loranne Agius Glucose and lipid metabolism in the fasted state OK Catherine Arden Biochemical mechanisms of insulin secretion Roy Taylor Insulin resistance from the receptor to the mouthful Mike Trenell Fit to function: assessing physical activity and fitness Quentin Anstee Liver disease in diabetes Philip Home Designing a good clinical trial Philip Home Monitoring and conducting a clinical trial Sally Marshall Factors contributing to the development of complications in diabetes Nicky Leech Prediction and immunotherapeutic intervention in Type 1 diabetes Jim Shaw Transplantation and regenerative medicine approaches for diabetes Dermot Neely Lipids in diabetes Mark Walker and Mike Trenell Practical session, Clinical Research Facility, Royal Victoria Infirmary. Nicky Leech & Rudy Bilous Seminar Design an outcome trial for a new glucose lowering drug Stuart Little Seminar How can technology help improve diabetes care? Jola Weaver Vascular studies in diabetes Linda Penn Type 2 diabetes prevention – population and individual approaches Roy Taylor Practical session MRI techniques Magnetic Resonance Centre, CAV
Assessment Deadlines: Assessment Details
Deadline
Written Examination (60%)
Week commencing 25th January 2016
In-course assessment: Written Report (20%)
Friday 18 December 2015, 1200 h
Oral Presentation (20%)
Wed 4 January 2016, 1400 h onwards (NESS submission deadline 1000 h, Wed 4 January 2016)
Recommended Reading and Other Resources: Reading list online: https://rlo.ncl.ac.uk/modules/MMB8035/2015
General Introduction: International Diabetes Federation www.idf.org Diabetes UK www.diabetes.org.uk American Diabetes Association www.diabetes.org
Other specific texts will be given at the end of each lecture
MSc in Medical Sciences – Faculty of Medical Sciences 2015/2016
Module Name:
Neuromuscular Diseases: Bench to Bedside
Module Code:
MMB8036
Module Leader Name/Email:
Dr Michela Guglieri
[email protected]
Other Teaching Staff: Name
Email Address
Prof. Kate Bushby
[email protected]
Prof. Clarke Slater
[email protected]
Dr Tuomo Polvikoski
[email protected]
Dr Richard Charlton
[email protected]
Dr Anna Sarkozy
[email protected]
Dr Ana Topf
[email protected]
Dr Iakowos Karakesisoglou
[email protected]
Dr Rita Horvath
[email protected]
Prof. Hanns Lochmüller
[email protected]
Prof. Annemieke Aartsma-Rus
[email protected]
Prof. Volker Straub
[email protected]
Dr Umar Burki
[email protected]
Dr Pauline McCormack
[email protected]
Dr Amina Chaouch
[email protected]
Dr Anna Mayhew
[email protected]
General Introduction: Neuromuscular diseases (NMDs) are rare, highly debilitating genetic conditions affecting the voluntary muscles, motor neurons or neuromuscular junctions. NMDs, such as muscular dystrophy or spinal muscular atrophy, frequently present in childhood and cause significant disability and early mortality. While each disease is relatively rare, collectively these conditions constitute a significant burden to both the patients and healthcare system. The neuromuscular diseases module focuses on translational approaches which are being undertaken both in Newcastle and globally to develop, test and ultimately deploy therapeutics to treat these devastating disorders.
Aims: 1. 2. 3. 4.
To instruct students in the process of translating research from bench to bedside using the example of a group of disabling and rare diseases To explore the challenges and promise of the “post genomic era” as related to a specific group of diseases in terms of understanding the underlying cause of disease and the possible therapies which may be suggested as a result of this understanding To facilitate students’ development of an appreciation of the novel methods of gene and other advanced therapies as they apply to the neuromuscular system To develop students’ understanding of the role of cellular and animal models in moving therapies into practice and the design of preclinical experiments
Outline of Syllabus: The module will cover: •
How neuromuscular diseases impact on normal muscle structure and function, including normal muscle function and physiology, and the clinical and electrophysiological manifestations of muscle dysfunction across the neuromuscular system.
•
The molecular pathology of neuromuscular diseases, including the application of next generation sequencing and the development of gene and protein based diagnostics. Students will meet patients with neuromuscular diseases.
•
The assessment of therapeutic strategies through the preclinical modelling and assessment of neuromuscular diseases using cellular and animal systems, including critical appraisal of claims of therapeutic success in the preclinical setting.
•
The state of the art of novel therapeutic strategies for neuromuscular diseases including gene and cell based therapies; understanding the targets and use of biomarkers; genetic and stem cell-based therapy for neuromuscular diseases; applications of antisense oligonucleotide technology in neuromuscular diseases; other targets for therapy development including downstream targets and protein up regulation. Moving studies into patients; the challenges of trial design in rare diseases.
Learning Outcomes: Intended Knowledge Outcomes: At the end of the module students should be able to: 1. Classify and discuss the different types of neuromuscular diseases and their molecular pathology, the burden of these diseases and their societal impact. 2. Discuss how the factors above define experiments aiming at the development of diagnostics and therapeutics 3. Discuss the challenges of post genome technologies in translation to patient benefit, using neuromuscular disease as an example 4. Evaluate different models of preclinical testing for therapy development and identify where these would be appropriate to use and where the limitations of such
5.
models lie Explain the pathway for translational research and discuss its challenges for a group of rare diseases
Intended Skill Outcomes: At the end of this module students should be able to: 1. Distinguish the broad categories of neuromuscular diseases and explain how molecular testing can precisely identify them 2. Utilise the tools available to interpret the results of next generation sequencing results 3. Choose the appropriate animal or cellular model for a preclinical experiment in neuromuscular diesase and describe the components of successful experimental design to provide the data to move forward into human studies 4. Assimilate data from recent journals and judge this critically in relation to the potential for therapy development by different techniques 5. Analyse critically the prospects for therapy in these conditions based on the cutting edge application of gene and cell based therapies 6. Present the synthesis of information from recent publications gathered individually and within a group to lecturers and peers
Starting Level of Module: This module deals with many aspects of neuromuscular diseases and is suitable for anyone with a background in biological, dental or medical sciences who enters the masters programmes. The module is designed to provide specialised, state-of-art knowledge most appropriate to those wishing to undertake research in this field. This systematic and integrated course is delivered by clinicians and scientists working in this field as basic researchers, primary physicians, diagnostic specialists and leading clinical researchers.
Schedule of Lectures: Thursday 08/10/2015
Thursday 15/10/2015
Thursday 22/10/2015 Thursday 29/10/2015 Thursday 05/11/2015
Overview of Course and assignment of project topics Introduction to normal muscle structure and function Understanding the molecular basis and molecular pathology of NMD Genetic heterogeneity and the particular challenges of diagnosis in NMD Detecting impairment of neuromuscular transmission and its effects on muscle properties Muscle pathology as a guide to diagnosis of inherited neuromuscular diseases Meet the Patients Promises, challenges and applications of next generation sequencing to neuromuscular disease Practical session on NGS Analysis Design and characterization of experiments to assess therapy development Mouse models for neuromuscular diseases
Thursday 12/11/2015 Thursday 19/11/2015 Thursday 26/11/2015 Thursday 03/12/2015 Thursday 10/12/2015
Thursday 17/12/2015 Thursday 07/01/2016 Thursday 14/01/2016
Applications of antisense oligonucleotide technology in NMD Stem cell and Gene therapy for NMD: challenges and progress Assessed Presentations I Zebrafish models for neuromuscular disease Cell culture- uses and limitations for modelling neuromuscular disease. Stem cell models. Ethical Issues around NMD Research Clinical Trial Design, Understanding the Target, Outcome Measures, Patient Recruitment and the Challenges of Rare Diseases Lesson from other therapeutic developments Assessed Presentations II MCQ Exam Revision Session
Assessment Deadlines: Assessment Details
Deadline
Written Examination (50%)
Week commencing 25th January 2016
In-course assessment: Assessed seminar 1 (20%) Assessed seminar 2 (20%)
Multiple Choice Questions [MCQ] (10%)
Thursday 19/11/2015 (NESS submission Wednesday 18/11/2015)
12
noon,
Thursday 17/12/2015 (NESS submission Wednesday 16/12/2015)
12
noon,
Thursday 07/01/2016, 3pm
Recommended Reading and Other Resources: Introductory background reading MacIntosh, B.R., Gardiner, P.F., & McComas, A.J., ‘Skeletal Muscle’, 2nd ed. (Human Kinetics, 2006). A good introduction to the biology and pathology of mammalian skeletal muscle. Book available in the Walton Library catalogue. Slater, C.R. (2008). Reliability of neuromuscular transmission and how it is maintained, in Handbook of Clinical Neurology Vol. 91, ‘Neuromuscular Junction Disorders’, ed. Engel, A.G. This volume contains many other potentially relevant articles. (pdf available.) Karpati (Ed) et al. ‘Disorders of Voluntary Muscle.’
Essential reading Bushby K, Lochmüller H, Lynn S, Straub V. (2009). Interventions for muscular dystrophy: molecular medicines entering the clinic. Lancet. 374(9704):1849-56 Bushby K. (2009). Diagnosis and management of the limb girdle muscular dystrophies. Pract Neurol 2009;9:314-323 Campbell, KP. (1995). Three muscular dystrophies: Loss of cytoskeleton-extracellular matrix linkage. Cell 80(5): 675-679. Fairclough RJ, Wood MJ, Davies KE. (2013). Therapy for Duchenne muscular dystrophy: renewed optimism from genetic approaches. Nat Rev Genet. 14(6):373-8. Müller JS, Mihaylova V, Abicht A, Lochmuller H (2007) Congenital myasthenic syndromes: spotlight on genetic defects of neuromuscular transmission. Expert Rev Mol Med 9:1–20 Udd B, Krahe R. (2012). The myotonic dystrophies: molecular, clinical, and therapeutic challenges. Lancet Neurol. 11(10):891-905 Vasli N, Laporte J. Impacts of massively parallel sequencing for genetic diagnosis of neuromuscular disorders. Acta Neuropathol. 2013 Feb;125(2):173-85 Further reading Journals: Babee TW, et al. (2012). Mouse models of SMA: tools for disease characterization and therapeutic development. Human Genetics. 131(8):1277-93 http://www.ncbi.nlm.nih.gov/pubmed/22543872 Benatar, M. (2007). Lost in translation: Treatment trials in the SOD1 mouse and in human ALS. Neurobiol. Dis. 26: 1-13. Blain AM, Straub VW. δ-Sarcoglycan-deficient muscular dystrophy: from discovery to therapeutic approaches. Skelet Muscle. 2011 Mar 17;1(1):13. doi: 10.1186/2044-5040-1-13. http://www.ncbi.nlm.nih.gov/pubmed/21798091 Blain A, et al. Animal Models of Duchenne Muscular Dystrophy, with Special Reference to the mdx Mouse. Journal of Biocybernetics and Biomedical Engineering. 2012. 32(4). http://www.ibib.waw.pl/?act=show&kat=171 Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, Kaul A, Kinnett K, McDonald C, Pandya S, Poysky J, Shapiro F, Tomezsko J, Constantin C; DMD Care Considerations Working Group. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 2010 Jan;9(1):77-93. Chevessier F. A new mouse model for the slow-channel congenital myasthenic syndrome induced by the AChR εL221F mutation. Neurobiol Dis. 2012 Mar;45(3):851-61. http://www.ncbi.nlm.nih.gov/pubmed/22178625 De Luca A. Pre-clinical drug tests in the mdx mouse as a model of dystrophinopathies: an overview. Acta Myol 2012 May;31(1):40-7. http://www.ncbi.nlm.nih.gov/pubmed/22655516
Dick E, Matsa E, Bispham J, Reza M, Guglieri M, Staniforth A, Watson S, Kumari R, Lochmüller H, Young L, Darling D, Denning C. Stem Cell Res. 2011 Mar;6(2):158-67. Gomes-Pereira M, et al. Myotonic dystrophy mouse models: towards rational therapy development. Trends Mol Med. 2011 Sep;17(9):506-17. http://www.ncbi.nlm.nih.gov/pubmed/21724467 Hornsey MA et al. Muscular dystrophy in dysferlin-deficient mouse models. Neuromuscular disorders 2013 May;23(5):377-87. http://www.ncbi.nlm.nih.gov/pubmed/23473732 Hilbert JE, Ashizawa T, Day JW, Luebbe EA, Martens WB, McDermott MP, Tawil R, Thornton CA, Moxley RT 3rd. Diagnostic odyssey of patients with myotonic dystrophy. J Neurol. 2013 Jun 27. Kaplan JC. The 2012 version of the gene table of monogenic neuromuscular disorders. Neuromuscul Disord. 2011 Dec;21(12):833-61. Konieczny P, Swiderski K, Chamberlain JS. Gene and cell-mediated therapies for muscular dystrophy. Muscle Nerve. 2013 May;47(5):649-63 Klinge L, Dekomien G, Aboumousa A, Charlton R, Epplen JT, Barresi R, Bushby K, Straub V. Sarcoglycanopathies: can muscle immunoanalysis predict the genotype? Neuromuscul Disord. 2008 Dec;18(12):934-41. Lemmers RJ, O'Shea S, Padberg GW, Lunt PW, van der Maarel SM. Best practice guidelines on genetic diagnostics of Facioscapulohumeral muscular dystrophy: workshop 9th June 2010, LUMC, Leiden, The Netherlands. Neuromuscul Disord. 2012 May;22(5):463-70. Lemmers RJ, Tawil R, Petek LM, Balog J, Block GJ, Santen GW, Amell AM, van der Vliet PJ, Almomani R, Straasheijm KR, Krom YD, Klooster R, Sun Y, den Dunnen JT, Helmer Q, Donlin-Smith CM, Padberg GW, van Engelen BG, de Greef JC, Aartsma-Rus AM, Frants RR, de Visser M, Desnuelle C, Sacconi S, Filippova GN, Bakker B, Bamshad MJ, Tapscott SJ, Miller DG, van der Maarel SM. Digenic inheritance of an SMCHD1 mutation and an FSHDpermissive D4Z4 allele causes facioscapulohumeral muscular dystrophy type 2. Nat Genet. 2012 Dec;44(12):1370-4. Norwood F, de Visser M, Eymard B, Lochmüller H, Bushby K; EFNS Guideline Task Force. EFNS guideline on diagnosis and management of limb girdle muscular dystrophies. Eur J Neurol. 2007 Dec;14(12):1305-12. Partridge TA. The mdx mouse model as a surrogate for Duchenne muscular dystrophy. FEBS J. 2013 Mar 28. http://www.ncbi.nlm.nih.gov/pubmed/23551987 Sleigh JN et al. The contribution of mouse models to understanding the pathogenesis of spinal muscular atrophy. Dis Model Mech. 2011 Jul;4(4):457-67. http://www.ncbi.nlm.nih.gov/pubmed/21708901 Straub V, Carlier PG, Mercuri E. TREAT-NMD workshop: pattern recognition in genetic muscle diseases using muscle MRI: 25-26 February 2011, Rome, Italy. Neuromuscul Disord. 2012 Oct 1;22 Suppl 2:S42-53. Tedesco FS, Gerli MF, Perani L, Benedetti S, Ungaro F, Cassano M, Antonini S, Tagliafico E, Artusi V, Longa E, Tonlorenzi R, Ragazzi M, Calderazzi G, Hoshiya H, Cappellari O, Mora M, Schoser B, Schneiderat P, Oshimura M, Bottinelli R, Sampaolesi M, Torrente Y, Broccoli V, Cossu G. Transplantation of genetically corrected human iPSC-derived progenitors in mice with limb-girdle muscular dystrophy. Sci Transl Med. 2012 Jun 27;4(140)
Vainzof, M. Animal models for genetic neuromuscular diseases. J Mol Neurosci. 2008 Mar;34(3):241-8. http://www.ncbi.nlm.nih.gov/pubmed/18202836 Vasli N, Böhm J, Le Gras S, Muller J, Pizot C, Jost B, Echaniz-Laguna A, Laugel V, Tranchant C, Bernard R, Plewniak F, Vicaire S, Levy N, Chelly J, Mandel JL, Biancalana V, Laporte J. Next generation sequencing for molecular diagnosis of neuromuscular diseases. Acta Neuropathol. 2012 Aug;124(2):273-83. Watchko JF. Decoding pathogenesis of slow-channel congenital myasthenic syndromes using recombinant expression and mice models. P R Health Sci J. 2010 Mar;29(1):4-17. http://www.ncbi.nlm.nih.gov/pubmed/20222328 Websites: http://neuromuscular.wustl.edu/ This website has a lot of useful information about the neuromuscular system and its disorders. http://www.treat-nmd.eu/research/preclinical/overview/ http://www.treat-nmd.eu/research/clinical-research/clinical-research-patients/ http://www.dmd.nl/
MSc in Medical Sciences – Faculty of Medical Sciences 2015/2016
Module Name:
Cardiovascular Science in Health and Disease
Module Code:
MMB8037
Module Leader Name/Email:
Professor Michael Taggart
[email protected]
Other Teaching Staff: Name
Email Address
Dr Dingchang Zheng
[email protected]
Dr Wing-Chiu Tong
[email protected]
Dr Djordje Jakovljevic
[email protected]
Prof Nick Europe-Finner
[email protected]
Prof Ioakim Spyridopoulus
[email protected]
Prof Deborah Henderson
[email protected]
Dr Guy MacGowan
[email protected]
Prof Helen Arthur
[email protected]
Dr Gendie Lash
[email protected]
Prof Azfar Zaman
[email protected]
Dr Vijay Kunadian
[email protected]
Prof Michael Trenell
[email protected]
Dr Andrew Owens
[email protected]
Prof Judith Rankin
[email protected]
General Introduction: Cardiovascular disease is the single biggest contributor to death and, as such, is one of the most important areas of global research. The programme in Cardiovascular Science in Health & Disease, encompassing a specifically tailored taught module and 6-month cardiovascular research project, will be delivered by scientific and clinical experts from 3 research Institutes of the Faculty of Medical Sciences (Institute of Cellular Medicine, Institute of Genetic Medicine, Institute of Health and Society). This gives a broad perspective to the topic rooted in current state-of-the-art research knowledge emanating from Newcastle and beyond. The taught module will cover: development of the heart, cardiac E-C coupling, vascular development and physiological remodelling, diseases of coronary arteries and cardiac valves, cardiac arrhythmias and heart failure. Research projects are available in a broad range of cardiovascular topics examples of which include: genetic and transcriptomic control of cardiac and vascular remodelling, microscopic assessment of cardiac structural remodelling, cardiac stem cells and angiogenesis, immune cells and myocardial ischaemia-reperfusion, biophysical assessments of cardiovascular function during exercise and in vivo imaging of cardiovascular disease. The programme will particularly suit scientists or clinicians with a strong interest in cardiovascular function and disease who aim to undertake research in this field.
Aims: This module gives students a detailed understanding of the development and function of the heart and vasculature and insight to the dysfunctional processes that underlie many cardiovascular diseases. The module will be taught by scientific and clinical research experts from several research Institutes of the Faculty of Medical Sciences (Institute of Cellular Medicine, Institute of Genetic Medicine, Newcastle Institute for Ageing and Health, Institute of Health and Society) giving a broad perspective to the topic rooted in current state-of-the-art research knowledge. The fundamentals of vascular and cardiac biology from molecular, cellular, tissue, organ and organisms perspectives will be described. Examples of model systems for the study of cardiovascular disease will be given throughout and complimented by descriptions of in vivo measurements of cardiovascular parameters in humans, disease identification and possible translation of research findings towards improved diagnosis and treatments. Lecturers will draw on examples from their own current areas of research activity. The module is compulsory for students wishing to proceed to an MRes in Cardiovascular Science in Health & Disease and will also be of interest to students wishing to attain an understanding of cardiovascular function and disease and/or progress towards a research career in this important topic.
Outline of Syllabus: Topics cover: The fundamentals of vascular structure and function (especially the relationship between endothelial cells, vascular smooth muscle cells and extracellular matrix), blood vessel development and remodelling in physiological circumstances (e.g. exercise and pregnancy) and how these processes may be aberrant in chronic disease conditions (e.g. ageing and coronary heart disease). Reference will be made to the use of experimental research models for understanding vascular structure and function in normal circumstances and disease. The fundamentals of cardiac cell and organ structure (cardiomyocyte striated structure to cell and tissue specialisations of the hearts 4 chambers), electrical excitability and contractile function (cardiomyocyte calcium handling to tissue and organ level study of excitation-contraction coupling). Descriptions will be given as to how these processes may be altered in common disease conditions (e.g. ageing and atrial and ventricular arrhythmias). Reference will be made to the use of experimental research models for understanding cardiac structure and function in normal circumstances and disease. The theoretical basis for, and applicability of, state-of-the-art in vivo measurement in humans of cardiovascular parameters important for the detection and diagnosis of, and improved treatment of, cardiovascular diseases.
Learning Outcomes: Intended Knowledge Outcomes: At the end of the module the students should be able to: • • • • • • • •
Explain how blood vessels develop and describe their structure and function Describe the mechanisms of tone regulation by endothelial and smooth muscle cells Detail important alterations in vascular structure and function with disease conditions Explain the key processes of cardiac organ development and cellular and tissue specialisations Describe the mechanisms of cardiac electrical excitation from cells to tissue and organ Discuss key alterations in cardiac function with disease Describe the use of in vivo measurement techniques of cardiovascular function in health and disease Be aware of and discuss current research activity designed to improve our understanding of cardiovascular structure and function in health and disease.
Intended Skill Outcomes: At the end of the module the students should have the ability to perform the following: • • •
Address in written essay form questions of relevance to the understanding of cardiovascular structure and function in health and disease. Use their knowledge to interpret and critically appraise scientific and clinical research literature in cardiovascular research. Perform short oral presentations on topics related to cardiovascular structure and function in health and disease.
•
Engage in discussions with their peers about fundamental molecular, cellular and tissue processes that regulate blood vessel and cardiac muscle function in health and disease, the current options for disease treatment and to speculate on how improved treatment options may arise.
Starting Level of Module: This module is designed to give students a breadth of understanding of normal cardiovascular function, the pathophysiological mechanisms that underlie cardiovascular disease and the clinical strategies involved in diagnosis, treatment and prevention of these scenarios. It is suitable for anyone with a background in biological, biophysical, dental or medical sciences who enters the masters programmes. It is designed to build on knowledge gained at undergraduate with a scientific and clinical research focus. The fundamentals of vascular and cardiac biology from molecular, cellular, tissue, organ and organisms perspectives will be described. This will be complimented by descriptions of in vivo measurements of cardiovascular parameters in humans, disease identification and possible translation of research findings towards improved diagnosis and treatments. Lecturers will draw on examples from their own current areas of research activity. The module will also be of interest to students wishing to attain a broad understanding of cardiovascular function and disease and/or progress towards a research career in this important topic.
Schedule of Lectures: Lecture 1 (MT). Lecture 2 (MT) Lecture 3 (DZ) Lecture 4 (MT) Lecture 5 (DJ) Lecture 6 (GNEF) Lecture 7 (DH) Lecture 8 (DH) Lecture 9 (WT) Lecture 10 (AZ) Lecture 11 (GM) Lecture 12 (HA) Lecture 13 (GL) Lecture 14 (HA) Lecture 15 (IS) Lecture 16 (IS) Lecture 17 (JR)
Introduction Vascular structure and function: physiology and pathophysiology In vivo assessment of vascular structure in health and disease Cardiac Excitation-contraction coupling Physical activity and cardiovascular function in health and disease β-adrenoceptor signalling in the heart Cardiac development Congenital Heart malformation Computational approaches to understanding cardiac function Coronary heart disease & interventions: acute coronary syndrome Cardiovascular ageing: myocardial conduction and E-C coupling Angiogenesis and vascular growth in health and disease I Angiogenesis and vascular growth in health and disease II Coronary vessel development Vascular inflammation & telomeres Coronary Heart Disease and Interventions: myocardial infarction Epidemiology of congenital heart diseases
Assessment Deadlines: Assessment Details
Deadline
Written Examination (60%)
Week commencing 25th January 2016
In-course assessment: 23rd
Essay (20%)
12 noon, deadline)
Group Oral Presentation (10%)
12 noon, 14th December 2015 (NESS deadline) Presentations will take place on 15th December
Individual Oral Presentation (10%)
12 noon, 4th January 2016 (NESS deadline) Presentations will take place on 5th January 2016
November
2015
(NESS
Recommended Reading and Other Resources: A good textbook for introduction to the fundamentals of cardiovascular biology is: Lecture Notes in Human Physiology. Editor Ole H Petersen. 5th Edition. Blackwell Publishing. Further reading guidance will be given at the time of individual lectures during the course. In addition, review articles (as well as original research papers of course) on scientific and clinical cardiovascular research topics feature prominently in the following journals: Circulation Circulation Research Cardiovascular Research Atherosclerosis, Thrombosis and Vascular Biology
