year 1 mcbom unit handbook 2013/14 - university of bristol

MB ChB PROGRAMME 2013-14

UNIT HANDBOOK

Molecular & Cellular Basis of Medicine

© University of Bristol 2013

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Contents Contents ............................................................................................................................................................ 1 Introduction ........................................................................................................................................................ 2 Overview ........................................................................................................................................................... 3 Key Dates .......................................................................................................................................................... 3 Staff Information ................................................................................................................................................ 4 Teaching Information ......................................................................................................................................... 4

Aims .............................................................................................................................................................. 4 Learning Outcomes ………………………………………………………………………………………………… .5 General Medical Council .................................................................................................................................. 12 Professional Behaviour .................................................................................................................................... 12 Teaching Information & Expected Student Input .............................................................................................. 12 Teaching Methods ........................................................................................................................................... 13

Lectures ....................................................................................................................................................... 13 Active Learning 2012-13 .............................................................................................................................. 13 Tutorials ....................................................................................................................................................... 14 Practicals & other class sessions ................................................................................................................. 14 Recommended Reading .............................................................................................................................. 15

Element 1 ........................................................................................................................................................ 16 Element 2 ........................................................................................................................................................ 26 Element 3 ........................................................................................................................................................ 32 Element 4 ........................................................................................................................................................ 39 Element 5 ........................................................................................................................................................ 44 Element 6 ........................................................................................................................................................ 48 Element 7 ........................................................................................................................................................ 54 Element 8 ........................................................................................................................................................ 57 Element 9 ........................................................................................................................................................ 66

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Introduction Welcome to the MCBoM Unit. In this Unit you will study how the body functions at the molecular and cellular level; which is central to understanding the causes of disease. Topics covered include basic anatomy, biochemistry, the molecular basis of cancer, cell biology, genetics, infection and immunity, nutrition, physiology and pharmacology. The science knowledge base gained from this Unit will enable you to progress to the Systems teaching, and to your subsequent clinical years. Moreover, this Unit will help you acquire a sound knowledge and understanding of the scientific basis of medicine, which will significantly improve your ability to make accurate diagnoses in your clinical years and future career. Some aspects of this Unit essentially form an interface between school and university. As such some of the topics we cover may be familiar to you from ‘A’ level, whereas others will be completely new. We will help you build on your present knowledge and understanding, expand it into new areas and introduce a medical perspective. The Unit Lead (Dr David J Morgan) and the Year 1 coordinator (Kirsty Bright) will communicate to you via email and Blackboard. You should check these frequently. This handbook should be read in conjunction with the Year 1 Handbook and the Rules, Policies and Procedures Handbook.

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Overview

The MCBoM Unit is subdivided into nine Elements; four in the first term and five in the second. Usually, two Elements will be presented in parallel. Term 1 introduces general principles underlying normal body function and Term 2 introduces the molecular basis of disease. The course is presented using an integrated, inter-departmental, approach and its teachers are drawn from the Centre for Comparative & Clinical Anatomy (CCCA) and the Schools of Biochemistry, Cellular & Molecular Medicine, and Physiology & Pharmacology.

MCBoM UNIT; PART 1 (Term 1) THE WORKINGS OF THE BODY

Element 1: Structural organisation of the body. Systems, organs, tissues and their

development.

Element 2: The molecular machinery of cells: proteins and enzymes, membranes, energy transformations and the dynamic

equilibrium.

Element 3: Functional organisation of the body. Excitable membranes, nervous transmission and muscle mechanics.

Introduction to homeostatic mechanisms.

Element 4: Metabolic homeostasis; tissue interactions in feeding, fasting and

exercise; regulation of metabolism by hormones.

MCBoM UNIT; PART 2 (Term 2) THE MOLECULAR BASIS OF DISEASE

Element 5: Manipulation of homeostasis: the principles of pharmacology.

Element 8: Infectious diseases, inflammation & immunity.

Element 6: Molecular genetics and genetic disease, & embryogenesis.

Element 9: Diseases of cell proliferation: tissue homeostasis and cancer.

Element 7: Metabolic and nutritional diseases.

Key Dates The term dates for 2013-2014 can be found at:

http://www.bristol.ac.uk/university/dates/

http://www.bristol.ac.uk/medical-school/staffstudents/student/termdates1314.pdf The provisional dates for examinations can be found at: http://www.bris.ac.uk/medical-school/staffstudents/assessments/students/ Please note that all examinations are compulsory.

These dates are for information only; please check before booking holiday flights.

http://www.bristol.ac.uk/university/dates/

http://www.bristol.ac.uk/medical-school/staffstudents/student/termdates1314.pdf

http://www.bris.ac.uk/medical-school/staffstudents/assessments/students/

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Staff Information For academic enquiries you should contact the appropriate Element lead listed in the table below.

Element Title Organiser School

Element 1 Structural Organisation of the Body

Ms Liz Gaze Centre for Comparative & Clinical Anatomy

Element 2 Proteins, Membranes & Cellular Activity

Dr Steve Burston School of Biochemistry

Element 3 Functional Organisation of the Body

Prof Sergey Kasparov School of Physiology & Pharmacology

Element 4 Homeostatic Mechanisms & Metabolic Homeostasis

Dr Elinor Griffiths School of Biochemistry

Element 5 Intervention in Homeostasis Prof Graeme Henderson School of Physiology & Pharmacology

Element 6 Introduction to Genetics, Genetic Diseases & Molecular Genetics

Dr Jan Frayne School of Biochemistry

Element 7 Nutrition & Metabolic Diseases Dr Kelly Moule & Dr Elinor Griffiths

School of Biochemistry

Element 8 Infection & Immunity Dr David Morgan School of Cellular & Molecular Medicine

Element 9 The Molecular Basis of Cancer Dr David Morgan School of Cellular & Molecular Medicine

Please do feel free to contact individual lecturers with specific queries during the year. All lecturers are named on the lecture synopsis and the contact details for everyone in the University, staff and students, can be found via the front page of the University website, www.bristol.ac.uk For all curriculum and teaching matters please contact the Year 1 Admin Coordinator Kirsty Bright in the Curriculum Office ([email protected]).

For pastoral support you can contact the Faculty Student Advisor Emma Teakle ([email protected]) or MB ChB Pre-Clinical Programme Director (Dr Eugene Lloyd).

Full details of student support services are available on Blackboard and http://www.bristol.ac.uk/medical-school/

Teaching Information Aims 1. To provide the student with appropriate knowledge and understanding of the basic sciences in preparation for their systems teaching, clinical studies and/or an intercalated Honours degree in a biomedical science.

2. To provide academic support, feedback and guidance for students from lecturers, tutors and the Unit organiser.

3. To ensure that the assessment procedures are fair, valid, transparent, reliable and in accordance with University Rules and Regulations.

4. To utilise the facilities of the Centre for Excellence in Teaching and Learning (CETL) in Applied and Integrated Medical Sciences (AIMS) to enrich the learning environment.

5. To encourage students to take responsibility for their learning in preparation for continuing professional development and lifelong learning.

http://www.bristol.ac.uk/

mailto:[email protected]

mailto:[email protected]

http://www.bristol.ac.uk/medical-school/

http://www.bristol.ac.uk/medical-school/

Molecular and Cellular Basis of Medicine Unit, Systems of the Body 1 & 2

Teaching and Learning

Assessment

Examples from the elements

Formats Year/s Assessment format Summative / formative /

both?

Outcomes 1 - Scholar and a Scientist

8 Apply to medical practice biomedical scientific principles, method and knowledge relating to: anatomy, biochemistry, cell biology, genetics, immunology, microbiology, molecular biology, nutrition, pathology, pharmacology and physiology.

Lectures, practicals, tutorials, case studies,

simulation sessions, computed aided learning and self directed learning

1 2 4

“Best of five” multiple choice questions, extended matching questions, data interpretation

questions, anatomy and histology assessment

Both

8a Explain normal human structure and functions. 1 2 Both

8b Explain the scientific bases for common disease presentations. 1 2 4 Both

8c Describe the use of common investigations. Lung function tests, electrocardiography, urinalysis, x-ray etc

3 4 5 Both

8d Explain the fundamental principles underlying such investigative techniques. 3 4 5 Both

8e Outline appropriate forms of management for common diseases, and ways of preventing common diseases, and explain their modes of action and their risks from first principles.

3 4 5 Both

8f Demonstrate knowledge of drug actions: pharmacodynamics and pharmacokinetics; drug side effects and interactions, and non-prescribed medication; and also including effects on the population, such as the spread of antibiotic resistance.

1 3 4 5 Both

8g Make accurate observations of biomedical phenomena and appropriate analysis and interpretation of biomedical data.

1 2 3 4 5

Both

9a Explain normal human behaviour at an individual level. 1

Human Basis Of Medicine (Society Health & Medicine & Whole Person Care)

1 Observation in small groups, tutorials,

essays & written examinations Both

9b Discuss psychological concepts of health, illness and disease. 1 4

Human Basis Of Medicine (Society Health & Medicine & Whole Person Care) & COMP2

1 4 Observation in small groups, tutorials,


9c Apply theoretical frameworks of psychology to explain the varied responses of individuals, groups and societies to disease.

1 Human Basis Of Medicine (Society Health &

Medicine & Whole Person Care) 1

Observation in small groups, tutorials, essays & written examinations

Both

9d Explain psychological factors that contribute to illness, the course of the disease and the success of treatment. 1 4

Human Basis Of Medicine (Society Health & Medicine & Whole Person Care) & COMP2



9e Discuss psychological aspects of behavioural change and treatment compliance. 4 COMP 2 has a workshop dedicated to this 4 Role play, facilitated by tutor + OSCE Both

9f Discuss adaptation to major life changes, such as bereavement. Compare and contrast the abnormal adjustments that might occur in these situations. 1 5

Human Basis Of Medicine (Society Health & Medicine + Whole Person Care) & Oncology & Palliative Care all have teaching sessions

dedicated to these topics



LEARNING OUTCOMES 2013/14

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9g Identify appropriate strategies for managing patients with dependence issues and other demonstrations of self-harm. 3 4 5

Psychiatry & Ethics, COMP 2 (tobacco & alcohol dependence) & Senior Medicine

1 4 5 MCQ, EMQ & OSCE Both

10 Apply social science principles, method and knowledge to medical practice. 1

Human Basis of Medicine (Society Health & Medicine)



10a Explain normal human behaviour at a societal level. 1

Human Basis Of Medicine (Society Health & Medicine & Whole Person Care)



10b Discuss sociological concepts of health, illness and disease. 1

Human Basis Of Medicine (Society Health & Medicine)



10c Apply theoretical frameworks of sociology to explain the varied responses of individuals, groups and societies to disease. 1

Human Basis of Medicine (Society, Health & Medicine)



10d Explain sociological factors that contribute to illness, the course

of the disease and the success of treatment including issues relating to health inequalities, the links between occupation and health and the effects of poverty and affluence.

1 4 5

Human Basis Of Medicine (Society Health & Medicine). COMP 1 (Public Health) has as its learning objective "Describe magnitude and trends in UK socioeconomic inequalities and goals to combat global inequalities in health". Emergency Medicine course in Yr5 teaches

this too.



10e Discuss sociological aspects of behavioural change and treatment compliance 1 4

Human Basis Of Medicine (Society Health & Medicine) & COMP 1 (Public Health)



11 Apply to medical practice the principles, method and knowledge of population health and the improvement of health and health care.

1 4

Human Basis of Medicine (Society Medicine & Health), COMP1 (Child Health & Public

Health). COMP1 includes this objective "Define public health and distinguish different types and approaches to disease prevention

and health strategies"

1 4 Tutorials & written examinations Both

11a Discuss the wider determinants of health and biomedical aspects of health improvement. 1 4 Both

11b Assess how health behaviours and outcomes are affected by the diversity of the patient population. 1

Human Basis Of Medicine (Society Health & Medicine)



11c Describe measurement methods relevant to the improvement of clinical effectiveness and care. 1 4

Human Basis of Medicine (Clinical Epidemiology) puts a strong emphasis on

this. Revised in COMP 1 1

Essay, MCQ & EMQ + data interpretation

Both

11d Discuss the principles underlying the development of health and health service policy, including issues relating to health economics and equity, and clinical guidelines.

1 4 Human Basis Of Medicine (Society Health &

Medicine). COMP 1 (Public Health) 1 4

Observation in small groups, tutorials, essays & written examinations

Both

11e Explain the basic principles of communicable disease control.

4 Both

11f Evaluate and apply epidemiological data in managing healthcare for the individual and the community. 1 4

Human Basis of Medicine (Clinical Epidemiology) & COMP1 (Public Health

1 4 Written examination Summative

11g Describe the role of environmental and occupational hazards in ill-health. ? Both

11h Discuss the role of nutrition in health. 4 5 Both

11i Discuss the principles and application of primary, secondary and tertiary prevention of disease 4 COMP2 puts a strong emphasis on this 4 MCQ, EMQ & OSCE Both

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11j Discuss from a global perspective the determinants of health and disease and variations in health care delivery and medical practice.

1

Human Basis of Medicine (Clinical Epidemiology & Whole Person Care).

Students also have opportunities to learn about this in an SSC & in an intercalated

degree

1 Both

12 Apply scientific method and approaches to practicals. 1 4 Both

12a Analyse and interpret data obtained in laboratory practicals 1 4 Both

12b Appreciate the importance of controls and repeat measurements when formulating simple relevant research questions in biomedical science.

1 4 Both

12c Apply findings from the literature to answer questions raised by specific clinical problems.

1 4

Learning objectives in COMP1 includes "demonstrate an ability to weigh up several sources of evidence of different strengths, and arrive at a reasonable conclusion in

response to the clinical question"

1 4 EMQ MCQ & essay Both

12d Understand the ethical and governance issues involved in medical research. 3 Ethics element of Psychiatry & Ethics 3 Case study report & MCQ Both

Outcomes 2 - Practitioner

13 Carry out a consultation with a patient.

1 2 3 4 5 Primary Care element of HBoM, Introduction

to Clinical Skills & all units from year 3 onwards

2 3 4 5 Observation on clinical placements,

during role play, long cases & OSCEs Both

13a Take and record a patient's medical history, including family and social history, talking to relatives or other carers where appropriate.

2 3 4 5 Introduction to Clinical Skills & all units from

year 3 onwards 2 3 4 5

Observation on clinical placements, during role play, long cases & OSCEs

Both

13b Elicit patients’ questions, their understanding of their condition and treatment options, and their views, concerns, values and preferences



Observation on clinical placements, during role play, long cases & OSCEs

Both

13c Understand the anatomy and physiology relevant to the physical examination. 2 3 4 5 Both

13d Perform a mental-state examination.



Observation on clinical placements, during role play, observed long cases

& OSCEs Both

13g Provide accurate explanations of biomedical phenomena. 3 4 5 Both

14 Diagnose and manage clinical presentations.

3 4 5 All units from year 3 onwards 3 4 5 MCQ, EMQ, observation on clinical placements, observed long cases &

OSCEs Both

14a Interpret findings from the history, physical examination and mental-state examination, appreciating the importance of clinical, psychological, spiritual, religious, social and cultural factors.



Observation on clinical placements & observed long cases

Both

14b Make an initial assessment of a patient's problems and a differential diagnosis. Understand the processes by which doctors make and test a differential diagnosis.

3 4 5 All units from year 3 onwards 3 4 5 Observation on clinical placements,

observed long cases & OSCEs Both

14c Formulate a plan of investigation in partnership with the patient, obtaining informed consent as an essential part of this process. 3 4 5 All units from year 3 onwards 3 4 5

Observation on clinical placements, observed long cases & OSCEs

Both

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14d Use knowledge of anatomy and physiology to aid the interpretations the results of investigations such as x-rays and electrocardiography.

3 4 5 Both

15 Communicate effectively with colleagues using appropriate terminology. Tutorials All Formative

15c Communicate by spoken, written and electronic methods (including medical records), and be aware of other methods of communication used by patients. Appreciate the significance of non-verbal communication in the medical consultation.

All years

Human Basis of Medicine (GP attachments), Introduction to Clinical Skills & all units from

year 3 onwards. There are dedicated communications skills sessions throughout

years 2-5

3 4 5 Observation in role play & clinical settings, OSCE & DOSCE (writing

discharge summary) Both

17 Prescribe drugs safely, effectively and economically. 4,5 All units in these years 4 MCQ, EMQ, DOSCEs Both

17a Establish an accurate drug history, covering both prescribed and other medication. 2 3 4 & 5

Introduction to Clinical Skills & all units from year 3 onwards

3 4 5 OSCEs. In COMP2 OSCE students

have to take a drug history) Both

17b Plan appropriate drug therapy for common indications, including pain and distress. 3 4 5 All units in these years 3 4 5

Discussions on clinical placements, MCQs, EMQs, on-line assessments

& OSCE Both

17c Provide a safe and legal prescription.

4 5

In COMP2 students attend a prescribing workshop with pharmacy students and learn about prescribing for chronic diseases, minor

illness and disease prevention. In Senior Medicine & Surgery students learn how to

prescribe safely for common problems

4 5 OSCE Both

17d Calculate appropriate drug doses including accurate use of units. 4 5 Both

17e Provide patients with appropriate information about their medicines. 4 5

COMP2, COMP1, Senior Medicine & Surgery, Oncology & Palliative Care

4 5 Discussions on clinical placements,

MCQs, EMQs & OSCEs Both

17f Access reliable information about medicines. 4 5 Formative

17g Describe the common and/or major adverse reactions associated with commonly prescribed drugs.

17h Demonstrate awareness that many patients use complementary and alternative therapies, and awareness of the existence and range of these therapies, why patients use them, and how this might affect other types of treatment that patients are receiving.

1 Whole Person Care (Human Basis of

Medicine) & COMP2 1 Small group discussion & essays Both

18 Be aware of the relevant anatomy for the safe practice of practical procedures. 3 4 5 Both

18a Be able to perform a range of diagnostic procedures, as listed in Appendix 1 and measure and record the findings. 2 3 4 5 See appendix 1 See appendix 1 Both

18b Be able to perform a range of therapeutic procedures, as listed in Appendix 1. 2 3 4 5 See appendix 1 See appendix 1 Both

18c Be able to demonstrate correct practice in general aspects of practical procedures, as listed in Appendix 1. 2 3 4 5 See appendix 1 See appendix 1 Both

19 Use information effectively in a medical context.



Presentations on ward rounds and GP attachments, observed long cases, viva’s & assessment of portfolios

Both

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19a Keep accurate, legible and complete records of the results of practicals. 3 4 5 Formative

19b Make effective use of computers and other information systems, including storing and retrieving information. 4 5 Formative

19c Keep to the requirements of confidentiality and data protection legislation and codes of practice in all dealings with information.

1 2 3 4 5

All GP and hospital attachments (from Human Basis of Medicine onwards). The

ethics & law surrounding confidentiality are taught in Psychiatry & Ethics (year 3).

3 Written case report & MCQs Both

19d Access information sources and use the information in relation to patient care, health promotion, advice and information to patients, and research and education.

4 Primary Care element of COMP2 puts a

strong emphasis on this 4 Workshops/small group discussion Formative

19e Apply the principles, method and knowledge of health informatics to medical practice. 3 4 5 All units from year 3 onwards

Outcomes 3 - Professional

20 Behave according to ethical and legal principles including health and safety rules. All Formative

20a Know about and keep to the GMC’s ethical guidance and standards including Good Medical Practice, the ‘Duties of a doctor registered with the GMC’ and supplementary ethical guidance which describe what is expected of all doctors registered with the GMC.

All All All Formative

20b Demonstrate awareness of the clinical responsibilities and role of the doctor, making the care of the patient the first concern. Recognise the principles of patient-centred care, including self-care, and deal with patients’ healthcare needs in consultation with them and, where appropriate, their relatives or carers.

All All All Verbal feedback during each clinical

attachment Formative

20c Be polite, considerate, trustworthy and honest, act with integrity and abide by the University's rules and regulations. All Formative

20d Respect colleagues and others regardless of their age, colour, culture, disability, ethnic or national origin, gender, lifestyle, marital or parental status, race, religion or beliefs, sex, sexual orientation, or social or economic status.

1 3 4 5 Formative

20e Recognise the rights and the equal value of all people and how opportunities for some people may be restricted by others’ perceptions.

2 Disability Matters Course 2 Small group discussion Formative

20f Understand and accept the legal, moral and ethical responsibilities involved in protecting and promoting the health

of individual patients, their dependants and the public including vulnerable groups such as children, older people, people with learning disabilities and people with mental illnesses.

1 3 4 & 5 Human Basis of Medicine, Psychiatry & Ethics, COMP1, COMP2, Oncology &

Palliative Care 1 3 4 5

Essays, student presentations, EMQs, MCQs & OSCE stations

Both

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20g Demonstrate knowledge of laws, and systems of professional regulation through the GMC and others, relevant to medical practice, including the ability to complete relevant certificates and legal documents and liaise with the coroner or procurator fiscal where appropriate.

1 3 4 & 5 Human Basis of Medicine, Psychiatry & Ethics, COMP1, COMP2, Oncology &

Palliative Care 1 3 4 5

Essays, student presentations, EMQs, MCQs, on-line assessments & OSCE

stations Both

21 Reflect, learn and teach others. Tutorials, practicals and case studies

1 2 3 4 5

Formative

21a Acquire, assess, apply and integrate new knowledge, learn to adapt to changing circumstances. 5 Formative

21b Accept responsibility for your own learning and develop foundations for lifelong learning. 5 Formative

21c Continually and systematically reflect on practice and, whenever necessary, translate that reflection into action, using

improvement techniques and audit appropriately for example, by critically appraising the prescribing of others.

3 4 & 5 COMP 2, Senior Medicine & Surgery &

External SSCs 5

Opportunity to complete audits in years 3-5, unit log books, essays &

presentations for SSCs Both

21d Manage time and prioritise tasks, and work autonomously when necessary and appropriate. All Formative

21e Recognise own personal and professional limits and seek help from colleagues and academic staff when necessary. All Formative

21f Provide measured and accurate feedback on the quality of the course. 5 Formative

22 Learn and work effectively within a multi-professional team.

2 4 5

Time spent working on nursing shift in Introduction to Clinical Skills. Care of Elderly (COMP2) and Oncology & Palliative Care put

a strong emphasis on multi-disciplinary working.

4 5 Observation on clinical placements Formative

22a Understand and respect the roles and expertise of health and social care professionals in the context of working and learning as a multi-professional team. 3 4

Psychiatry & Ethics, COMP2 (Primary Care & Care of the Elderly) & COMP1 (Child Health) -all provide lectures, small group discussions

& direct experience of this.

3 4 Small group discussions, e.g. Case-base discussion of intermediate care

in Year 4 Disability Workshop Both

22b Understand the contribution that effective interdisciplinary team-working makes to the delivery of safe and high quality care.

2 3 4 5

Introduction to Clinical Skills & all units from year 3 onwards. For example one of

Psychiatry's learning objectives is "Describe the role of at least two different professionals

[non-medical] who can be involved in the provision of services to someone with these

type of mental health problems".

3 4 5 Essays (e.g. COMP2 SSC requires students to interview different health

professionals), viva & EMQs Both

22c Work with colleagues in ways that best serve the interests of patients, passing on information and handing over care, demonstrating flexibility, adaptability and a problem-solving approach.

2 3 4 5

Introduction to Clinical Skills & all units from year 3 onwards. For example learning objectives in Senior Medicine include

"Understand the necessity for accurate, informative and succinct clinical note taking."

4 5 Observation on clinical placements.

Writing discharge letter in OSCE Both

22d Demonstrate ability to undertake various team roles including leadership and the ability to accept leadership by others in practicals and tutorials.

4 5 Formative

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23 Protect patients and improve care. 1 2 3 4 5 Inherent within each unit 4 5

Essays (for example for COMP2 SSC) & small group discussions.

Both

23a Place patients’ needs and safety at the centre of the care process. 1 2 3 4 5 Inherent within each unit 4 5 Essays, small group discussions. Both

23b Deal effectively with uncertainty and change. 4 Primary Care teaching in COMP2 4 Observation on GP attachments Formative

23c Understand the framework in which medicine is practised in the UK, including: the organisation, management and regulation of healthcare provision; the structures, functions and priorities of the NHS; and the roles of, and relationships between, the agencies and services involved in protecting and promoting individual and population health.

3 4

Ethics provides teaching on the relationship between public & private healthcare in the

UK. COMP2 has as 2 of its learning objectives: "Describe the role of the GP and

the other members of the primary health care team" and

"Appraise the different systems providing open access health care in the UK". It offers lectures on role of Primary Care, NHS Direct & Walk-in-Centres. COMP1 provides some

teaching.

4 Case based discussions, discussion

with GP teachers & MCQs Both

23d Promote, monitor and maintain health and safety in the clinical setting, understanding how errors can happen in practice, applying the principles of quality assurance, clinical governance and risk management to medical practice, and understanding responsibilities within the current systems for raising concerns about safety and quality.

5 Senior Medicine & Surgery 5

Demonstration of ability to report a clinical incident is one of the learning objectives for year 5 (listed in Bristol's

core skills to become a doctor)

Formative

23e Understand and have experience of the principles and methods of improvement, including audit, adverse incident reporting and quality improvement, and how to use the results of audit to improve practice.

3 4 5 External SSCs 3 4 5 All students have to complete an audit

during at least one of their external SSCs.

Both

23f Respond constructively to the outcomes of appraisals and feedback from tutors.

All years

Formative

23g Demonstrate awareness of the role of doctors as managers, including seeking ways to continually improve the use and prioritisation of resources.

4 Students may gain some awareness of this by speaking to their GP teachers & possibly

consultants None

23h Understand the importance of, and the need to keep to, measures to prevent the spread of infection, and apply the principles of infection prevention and control.

2 4 5 Introduction to Clinical Skills, COMP1 &

Surgical Skills course 2 4 5 See rows 33, 37, 162, 163, 164 & 165 Both

23i Recognise own personal health needs, consult and follow the advice of a suitably qualified professional, and protect colleagues from any risk posed by own health.

All

years Formative

23j Recognise the duty to take action if a colleague’s health, performance or conduct is putting others at risk. Formative

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General Medical Council Blueprinting and standard setting are requirements of the General Medical Council that regulates medical education in the United Kingdom. You can read about their requirements as published in Tomorrow’s Doctors 2009 at the URL below:

http://www.gmcuk.org/education/undergraduate/tomorrows_doctors_2009.asp

Professional Behaviour You should adhere to the professional code of practice at all times which can be found at: www.medici.bris.ac.uk/student/copaccept This includes: - treating all patients with respect (including respecting confidentiality) - treating all staff and colleagues with respect (including not disrupting their teaching) - attending all teaching on time and adhering to the clinical dress code - being honest and handing in all required paperwork/assessments to deadlines - taking care of your health and seeking help if your health may impact on patient care

Teaching Information & Expected Student Input The learning opportunities in this Unit include lectures, practical classes, small group sessions and eLearning. The lectures provide a framework for your understanding; which is reinforced by small group tutorial sessions, including problem solving, and experiments in practical classes. It is imperative that you read the practical schedule before attending the session and complete any preparation for the small group sessions as required. In addition to these scheduled learning opportunities you are expected to take responsibility for your own learning through private study. As an absolute minimum you are expected to review your lecture notes in preparation for each subsequent lecture to ensure that you understand the key concepts and principles.

You are expected to comply with the health & safety instructions associated with working in the laboratory as listed in your handbook for practical classes.

Academic staff will use opportunities during practical classes and small group sessions to provide you with formative feedback about your performance.

In order to continue to improve and refine the course we will ask for your feedback using questionnaires posted on Blackboard. You are also most welcome to send feedback direct to the Unit Organiser.

Your attendance should be 100% for all teaching. Any absence must be reported on the day of absence, preferably by 9.30am. Email: [email protected] Absence from tutorials or practical classes will be reported to the administrative team. Persistent absenteeism is considered to be unprofessional behaviour. Offenders will be referred to the Professional Behaviour Panel and a note will appear on their records.

http://www.gmcuk.org/education/undergraduate/tomorrows_doctors_2009.asp

http://www.medici.bris.ac.uk/student/copaccept

https://mail.google.com/mail/?view=cm&fs=1&tf=1&[email protected]

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Teaching Methods Lectures These are normally 50 minutes in duration and are central to this part of the MB ChB programme. You will be given a lecture handout but it is important to make your own notes as well and to review them soon afterwards to make sure you understand the contents of the lecture. Power-point presentations and other learning material can be accessed via Blackboard. You should look back over your notes regularly; they will remind you about the lecture and enable you to review what you are learning and integrate it with other teaching so that you can draw on it in, for example, data handling or problem solving sessions. This will be invaluable when you come to revise for your exams. Punctuality is important, as a matter of courtesy to your fellow students and the lecturer. If you are late you should enter at the back of the lecture theatre to avoid disturbing others. Lecturers have the right to abandon lectures if there is too much noise for effective teaching and learning. Staff and students can make complaints about inappropriate behaviour under the Code of Professional Behaviour Procedure. Active Learning 2013-14 One of our key aims is to encourage you to develop an approach to learning that will be required in the clinical years and for lifelong learning as part of continuing professional development (CPD). This requires you to take responsibility for your own learning and engage in active learning techniques. Developing these skills takes time and you will find very helpful guidance in “How to Succeed at Medical School - an essential guide to learning” by Evans and Brown. As part of this process you are required to complete the template below for each lecture and element. Take a blank sheet of A4 paper and write the following questions, allowing space for your answers: What are the key messages/learning points in this lecture? How does it build upon what I already know? What are the links with other lectures/practical classes? How is this applied in clinical practice? What further studying do I need to do? Now try and answer the questions with the guidelines below. Don’t rush, the process takes time and requires you to think about the material. However it will be time that is well invested when it comes to revising your notes and preparing for the examinations. Don’t forget to include the date and title of the lecture! What are the key messages/learning points in this lecture? The learning objectives and summary may help you, as well as actively listening in the lecture for phrases such as “In summary…”, “Most importantly…”, “The key message I’m trying to get across is”. You may wish to use bullet points and/or concept maps. Most importantly, try and write it in your own words to aid understanding and make it easier to revise. Get into the habit of asking yourself questions to develop insight such as: Why is this important? How does this process work? What are the underlying principles? What can I do to make this easier to remember? How does it build upon what I already know? What are the links with other lectures/practical classes? Most of us learn by building upon prior knowledge and experience, so give a brief summary of what you already knew about the topic. Then try to identify links with practical classes and other lectures/elements. You will find some topics are covered more than once and this reinforcement is useful to identify important issues. You should also begin to integrate across the different biomedical disciplines. For example you will learn about the anatomy of the pancreas, the biochemistry and physiology of glucose homeostasis, the immunology of diabetes and pharmacology of therapy for diabetes. It is worth spending time learning to bring these different disciplines together for each of the major diseases that you study. How is this applied in clinical practice? Some lecturers may not make this explicit during their lecture but this an opportunity for you to engage in some detective work and find the answers. Invest in a textbook of medicine such as Clinical Medicine by Kumar & Clark or Principles and Practice of Medicine by Boon et. al. so that you can dip into it to see how your basic

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science learning is relevant to clinical practice. You can also use the Internet and discuss this with your peers, lecturers and tutors. http://www.healthtalkonline.org/ is an award-winning site that is highly recommended by previous students. You can find out about diseases from the perspective of patients and their care-providers. When you start learning in the clinical environment you’ll find that having taken this approach you’ll find it much easier to build upon prior learning and apply the basic sciences to the care of patients. What further studying do I need to do? You need to identify the gaps in your knowledge and/or skills seek out appropriate help and information. For example you might need to learn to search for scientific papers using PubMed and may be able to seek help from a librarian. There may be a list of new terms that you are not familiar with and will need to look them up in a textbook. You might need to do background reading to prepare for an assessment or find practice questions to attempt. You might need to develop or refine your study skills and seek help from the student advisor or attend one of the courses available at the Student’s union. Students often find it a shock adjusting to this learning approach at University when they are used to being told what to do at school (i.e. passive learning or ”spoon-feeding”). Adjusting to this new approach will take time and effort. It is estimated that it takes about three months of practice to become efficient at a new approach to learning. It is also estimated that a medical student is required to do approximately 10 hours per week of effective and productive private study i.e. study outside of lectures, practical classes and tutorials. The active learning template is a tool that you can use to help guide your private study. You can also compare your template to your colleagues. Some students might choose to set up private study groups to brainstem ideas to complete the template. Don’t worry about trying to achieve the perfect template or be tempting to simply copy a colleague’s attempt word-for-word. We’re all individuals with different learning styles and preferences, and different prior knowledge and learning needs. The important thing is to tailor your template to your needs. Medicine is a fascinating subject and an active approach to learn makes it more stimulating and enjoyable.

Tutorials You will receive tutorials most weeks from academic or research staff. These tutorials are to help you understand and assimilate the material presented in lectures and apply it to problem solving.

You will be allocated to a tutorial group containing about 10 students. A list of tutorial groups and rooms will be posted on Blackboard, our eLearning webpage. Each tutorial group will have a number of tutorials, arranged in 4 blocks. A list of tutors, their contact information and the venue of each group's tutorials will also be posted on the Blackboard site, along with any necessary changes in tutorials and messages from your tutor.

You must keep your marked tutorial work in a file, along with any practical accounts, so that if necessary they can be made available for inspection by the Examiners at the end of the year. Practicals & other class sessions You will normally attend two practical sessions each week. These include laboratory classes, problem-solving exercises, topographical anatomy sessions and histology classes. You should read the relevant section of the practical handbook and anatomy handbook in advance and ensure you arrive in time for the start of the session. Biochemistry, Physiology and Pharmacology practical pre-lab tests Before each practical, you must read the introductory material and practical schedule (in your practical book) and complete the pre-lab test. Biochemistry reference booklet We will provide you with a reference booklet that contains information on the biochemical pathways which are relevant to the unit. You will be provided with a copy of this booklet in your MCBoM examinations. We see no point in asking you to rote learn the details of metabolic pathways but we expect you to understand and apply your metabolic knowledge to clinical scenarios. The booklet also contains a number of important equations which you may need for data handling/interpretation questions.

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Recommended Reading All recommended textbooks are available from the Library; however they may be in short supply at times of high demand. You may wish to purchase some books of your own for personal reference. You certainly do not need to purchase all of the books listed. We suggest that you look at the books in the Medical Library before making your purchases, and choose those you feel best suit your approach. Remember that not all the material in each book is essential knowledge for each course. Full descriptions of these books can be found on www.amazon.co.uk. Go to the Books tab, click Advanced Search on the left hand side of the menu bar at the top of the screen and enter the ISBN number. Reading lists for the academic year 2013-14 are available through the ‘Library’ button on the MCBoM Blackboard course.

http://www.amazon.co.uk/

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ELEMENT 1

STRUCTURAL ORGANISATION OF THE BODY

SYSTEMS, ORGANS, TISSUES & THEIR DEVELOPMENT ELEMENT ORGANISER: Ms Liz Gaze, Centre for Comparative and Clinical Anatomy Element Teachers: Ms Liz Gaze, Dr Andrea Phillips, Medical Demonstrators

OVERVIEW This element contains 13 lectures. Please check your MCBoM timetable on Blackboard for venues. There are also 12 Dissection Room sessions in the Human Dissection Rooms (HDR’s 1 & 2) – a separate timetable is shown below. TIMETABLE

DATE TIME SESSION

Tues 1st October 14:00 1.1: Tissues of the Body I

Tues 1st October 15:00 1.2: Tissues of the Body II

Fri 4th October 10:00 1.3: Nervous System I

Fri 4th October 11:00 1.4: Nervous System II

Mon 7th October 14:00 1.5: Introduction to Medical Imaging

Fri 11th October 10:00 1.6: Thorax

Fri 18th October 11:00 1.7: Abdomen I

Fri 25th October 10:00 1.8: Abdomen II

Fri 1st November 11:00 1.9: Lower Limb

Fri 15th November 10:00 1.10: Upper Limb Weds 4

th December 09:00 1.11: Head & Neck I

Mon 9th December 10:00 1.12: Head & Neck II Mon 16

th December 12:00 1.13: Head & Neck III

AIMS

To provide an introduction to human anatomy (particularly at a regional level) that is appropriate to the early stages of medical training.

To equip students with a solid foundation of basic knowledge on which to build an advanced (systems based) understanding of anatomy that can be applied to clinical work later in the course.

To understand how the structure of the living body may be investigated using various types of medical imaging

To start the process of acquiring the 3-dimensional understanding of human anatomy that is necessary to safely perform practical procedures on patients.

OBJECTIVES By the end of the Element, students should:

understand the structure, functions and distributions of major tissue types (skin, adipose tissue, fascia, muscle, tendon, ligament, bone, artery, vein, nerve, viscera, lymph nodes and glands) and to be able to recognise the gross appearance of these tissues.

understand the organisation of the skeleton and the relationship between structure and function of individual bones and joints.

know the structure of a spinal nerve and its relationship to the spinal cord and to understand the concept of myotomes and dermatomes

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be able to list the anatomical features and organisation of the autonomic components of the nervous system

LECTURES Note: During the introductory week there will be a lecture about the ethical, emotional and legal aspects of human dissection. The information contained in that lecture is considered to be an integral part of the basic course in anatomy.

Lecture 1.1: Tissues of the body 1. Ms Liz Gaze. The structure and function of soft tissues including skin and skin appendages, fascia, tendons and ligaments. Questions:

What two main layers comprise skin?

Where is deep fascia found in the body?

Lecture 1.2: Tissues of the body 2. Ms Liz Gaze. The structure, function and classification of bones, joints and muscles. Question:

What factors determine the movement which occur at a particular joint?

How do functional requirements affect the shape and position of a muscle?

Lecture 1.3: Nervous System 1. Ms Liz Gaze. The segmental organization of the vertebral column and its relationship to the spinal cord and spinal nerves. Concepts of myotomes and dermatomes. Questions:

What are the peripheral routes by which a painful stimulus to the hand results in its withdrawal?

What do the terms dermatome and myotome mean?

Lecture 1.4: Nervous System 2. Ms Liz Gaze. Introduction to the arrangement of the autonomic nervous system. Questions:

What are the nervous connections/anatomical arrangements of the sympathetic ganglia?

Which nerve increases motility of the stomach? Lecture 1.5: Introduction to Medical Imaging. Dr AJ Phillips. The basic procedures, uses and limitations of various imaging modalities (conventional radiography, contrast studies, computed tomography, magnetic resonance imaging, ultrasound and scintigraphy) Questions:

Which imaging modalities are useful for visualising bony structure?

Which imaging modalities show soft tissue structures well? Lecture 1.6: Thorax. Ms Liz Gaze. Introduction to the structures comprising the thoracic wall, and the contents of the thorax. Questions:

What is the function of pleura?

How does blood flow through the heart?

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Lecture 1.7: Abdomen 1. Ms Liz Gaze. Introduction to peritoneal attachments, the inguinal canal and the neurovascular supply to the gut. Questions:

Within which peritoneal attachment is the jejunoileum contained?

The descending colon receives its blood supply from which major branch of the aorta? Lecture 1.8: Abdomen 2. Ms Liz Gaze. Introduction to the abdominal viscera, the kidney and the neuronal control of the bladder. Questions:

Which nerve supplies the external urethral sphincter?

Draw a picture of the gross internal structure of the kidney. Lecture 1.9: Lower limb. Ms Liz Gaze. Introduction to the bones, muscles, joints and neurovascular supply to the lower limb. Questions:

What are the ligaments of the knee joint and which movements do they support?

Which muscles are found in the posterior compartment of the thigh and what is their nerve supply? Lecture 1.10: Upper limb. Ms Liz Gaze. Introduction to the bones, muscles, joints and neurovascular supply to the upper limb. Questions:

Where is the median nerve often compressed and what are the clinical signs?

What is the arterial supply to the upper limb? Lecture 1.11: Head and neck 1. Ms Liz Gaze. Introduction to the skull and cranial nerves. Questions:

Which are the muscles of mastication and what is their nerve supply?

Which cranial nerves control movement of the eyeball?

Lecture 1.12: Head and neck 2. Ms Liz Gaze. Introduction to the structures in the head and neck including the pharynx and larynx. Questions:

What are the names of the 3 main cartilages of the larynx?

The superior thyroid artery is a branch of which vessel? Lecture 1.13: Head and neck 3. Ms Liz Gaze. Introduction to the brain, eye and ear. Questions:

Which artery supplies the visual cortex?

Name the ossicles of the middle ear.

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DISSECTION ROOM SESSIONS Venue: All practical sessions will be held in the Human Dissection Rooms (HDR’s 1 & 2) in the Department of Anatomy, Southwell Street. They will be taught by academic staff and medical demonstrators.

Staff Key: LG – Ms Liz Gaze, MD – Medical Demonstrators

DATE TIME GROUPS SESSION

Wed 2nd October 10:00 A9 – A12, B9 – B12

1: Terminology & tissues of the body LG, MD

Thurs 3rd October 10:00 B1 – B8

Fri 4th October 14:00 A1 – A8

Wed 9th October 10:00 A9 – A12, B9 – B12

2: The nervous system LG, MD

Thurs 10th October 10:00 B1 – B8


Wed 16th October 10:00 A9 – A12, B9 – B12

3: Thorax LG, MD



Wed 23rd October 10:00 A9 – A12, B9 – B12

4: Abdomen & pelvis 1 LG, MD



Wed 30th October 10:00 A9 – A12, B9 – B12 5: Abdomen & pelvis 2

LG, MD

Thurs 31st October 10:00 B1 – B8

Fri 1st November 14:00 A1 – A8

Wed 6th November 10:00 A9 – A12, B9 – B12 6: Lower limb 1

LG, MD

Thurs 7th November 10:00 B1 – B8

Fri 8th November 14:00 A1 – A8

Wed 13th November 10:00 A9 – A12, B9 – B12

7: Lower limb 2 LG, MD




8: Upper limb 1 LG, MD

Thurs 21st November 10:00 B1 – B8

Fri 22nd November 14:00 A1 – A8


9: Upper limb 2 LG, MD



Wed 4th December 10:00 A9 – A12, B9 – B12

10: Head & neck 1 LG, MD

Thurs 5th December 10:00 B1 – B8

Fri 6th December 14:00 A1 – A8




Fri 13th December 14:00 A1 – A8




Thurs 19th Dec 14:00 A1 – A8

Fri 20th December TBA All groups ANATOMY & HISTOLOGY ASSESSMENT

(formative)

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ELEMENT 2

PROTEINS, MEMBRANES & CELLULAR ACTIVITY

ORGANISATION

Element Organiser: Dr S Burston, School of Biochemistry, Medical Sciences Building Teaching Staff: Dr S Burston, Dr K Moule, Dr Elinor Griffiths and Dr Janet Frayne, School of

Biochemistry, Medical Sciences Building

This Element contains 19 lectures, 2 practicals, 1 workshop and 1 exam practice session. Please check your MCBoM timetable on Blackboard for venues of lectures. Practical sessions are held in TL 5.1.

TIMETABLE

Fri 4th October 12:00 2.1: Introduction to Biochemistry Dr Steve Burston

Mon 7th October 15:00 2.2: Protein Folding Dr Steve Burston

Wed 9th October 09:00 2.3: Clinical Applications Dr Steve Burston

Fri 11th October 11:00 2.4: Enzymes Dr Steve Burston

Fri 11th October 12:00 2.5: Myoglobin & Haemoglobin Dr Steve Burston

Mon 14th October 15:00 2.6: Fundamentals of gene expression Dr Janet Frayne

Wed 16th October 09:00 2.7: DNA Replication Dr Janet Frayne

Wed 16th October 10:00 Biochemistry Practical 1 (B1 - B8) Dr Janet Frayne

Thurs 17th October 09:00 2.8: Mutations & DNA Repair Dr Janet Frayne

Thurs 17th October 10:00 Biochemistry Practical 1 (A1 - A8) Dr Janet Frayne

Fri 18th October 12:00 2.9: RNA Synthesis and DNA transcription in prokaryotes I

Dr Janet Frayne

Fri 18th October 14:00 Biochemistry Practical 1 (A9 -A12, B9 - B12) Dr Janet Frayne

Mon 21st October 14:00 2.10: RNA Synthesis and DNA transcription in

prokaryotes II Dr Janet Frayne

Mon 21st October 15:00 2.11: Biological membranes Dr Kelly Moule

Mon 21st October 16:00 2.12: Transport of solutes across membranes Dr Kelly Moule

Wed 30th October 09:00 2.13: Transporter proteins and ion channels Dr Kelly Moule

Thurs 31st October 09:00 2.14: Introduction to metabolism I Dr Kelly Moule

Fri 1st November 12:00 2.15: Introduction to metabolism II Dr Kelly Moule

Mon 4th November 16:00 2.18: Mitochondria and the electron transport train Dr Elinor Griffiths

Wed 6th November 09:00 2.19: Oxidative phosphorylation; brown fat metabolism; mitochondrial DNA

Dr Elinor Griffiths

Wed 6th November 10:00 Biochemistry Practical 2 (B1 - B8) Dr Alice Robson

Thurs 7th November 10:00 Biochemistry Practical 2 (A1 - A8) Dr Alice Robson

Fri 8th November 09:00 2.16: The oxidation of fatty acids Dr Kelly Moule

Fri 8th November 10:00 2.17: The tricarboxylic acid cycle Dr Kelly Moule

Fri 8th November 14:00 Biochemistry Practical 2 (A9 - A12, B9 -B12) Dr Alice Robson

Fri 6th December 09:00 Biochemistry Exam Practice 1 (90 mins) Dr Janet Frayne

Tues 17th December 11:00 Data Handling Workshop (B1 – B8) Dr Janet Frayne

Tues 17th December 14:00 Data Handling Workshop (A9 – A12, B9 – B12) Dr Janet Frayne

Weds 18th December 11:00 Data Handling Workshop (A1 – A8) Dr Janet Frayne

DATE TIME SESSION STAFF

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AIMS

This Element aims to enable students to understand: the molecular machinery of cells, emphasising proteins (in particular the relationship between structure

and function) and biological membranes the energetic implications of cellular activity; the dynamic equilibrium through which maintenance of

body structure and function depends on the continuous expenditure of energy derived from the diet transmembrane concentration gradients, including respiration and energy transformations the major biochemical transformations within cells whereby energy is derived from fatty acids,

emphasising the importance of mitochondria the molecular basis of genetics, the relationship between gene expression, nucleic acids, and protein

synthesis.

PRE-REQUISITES

Before starting this module students should understand: basic biological terminology including the cellular structure of biological material the fundamental principles of chemistry (atomic structure and chemical bonding, the chemistry of

carbon compounds, functional groups and their reactivity, and equilibria and thermodynamics)

OBJECTIVES

By the end of this Element students should: understand the central role of proteins in cell structure and behaviour understand the relationship between amino acids and proteins and draw the peptide bond know the generic structure of amino acids and describe the different chemical classes of amino acids

according to the structure of their side chains know pH and its relationship to pKa through the Henderson-Hasselbach equation understand the ionisation of amino acid side chains and explain the concept of buffers know the primary, secondary, tertiary and quaternary levels of protein structure be able to list the physical and chemical forces which stabilise the 3-dimensional structure of proteins know the importance of correct protein folding with particular reference to the prion protein know the importance of structure and conformation to the biological activity and behaviour of proteins know the main methods for separating proteins and their use in clinical diagnosis comprehend the terms enzyme, cofactor and prosthetic group and explain what is meant by Km and

Vmax and their relationship to enzyme inhibition and the rate of enzyme-catalysed reactions

be able to list the major mechanisms for controlling enzyme activity be able to list with examples the use of enzyme assays in diagnosis understand how changes in molecular structure are related to function and disfunction in proteins know the difference between a cooperative and non-cooperative enzyme using haemoglobin and

myoglobin as examples and explain how haemoglobin is allosterically regulated be able to list the main kinds of lipids and their general properties and explain the formation of

phospholipids into bilayers be able to distinguish between integral and peripheral membrane proteins; describe the forces which

associate them with the membrane; describe the topology of integral membrane proteins and their structural features; discuss membrane asymmetry

know how unsaturated fatty acids and cholesterol affects membrane fluidity; list the main features of the fluid mosaic model of membrane structure; understand the restrictions on protein movement in membranes including interactions with the cytoskeleton

understand how the properties of solutes affect their movement through membranes; distinguish passive diffusion, facilitated and active transport; describe the main features of channel proteins

know the differences in ionic composition of the extracellular and intracellular fluids, the role of the Na/K-ATPase in regulating the ionic composition of the cytoplasm and discuss the mechanism of action of this ion pump

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know how sugars and amino acids are transported by cells using symports and antiports driven by the transmembrane Na-gradient

know what the role of reducing equivalents are within the cell understand the coupling of a thermodynamically favourable reaction to drive an unfavourable one and

the role of ATP in energy metabolism know what is meant by metabolism, anabolism and catabolism know the structure of fats and explain how they may be used as fuels via oxidative conversion into

acetyl CoA and explain the importance of NAD and FAD reduction understand the role of the citric acid cycle, the importance of acetyl CoA in metabolism and

mitochondrial compartmentation

understand the principles of oxidative phosphorylation and explain the coupling of respiration and ATP synthesis by the proton motive force (chemiosmotic theory)

understand the mechanism and sites of action of inhibitors and uncouplers of respiration and oxidative phosphorylation; explain the process and role of thermogenesis in brown adipose tissue, including the regulation of uncoupling proteins

know the basis of diseases arising from defects in the respiratory chain; have a basic understanding of the mitochondrial genome and proteins encoded by it

understand the properties and features of nucleic acids

know the structure of the DNA double helix , including base-pairing mechanisms

understand the general features of DNA replication and DNA repair mechanisms

know the structure of RNA and the different types of RNA molecules

understand the concept of gene promoters. Describe the mechanism of DNA transcription

LECTURE SYNOPSES & QUESTIONS

Lecture 2.1: Introduction to Biochemistry. Dr Steve Burston. The importance of proteins in nature. Protein architecture: amino acids, their side chains and the effect of pH on side chain ionisation (linked to group teaching sessions). The peptide bond. Protein structure: secondary, tertiary and quaternary levels. Questions:

List the general functions of protein molecules in cells.

What the generalised structure of an amino acid is.

What is the chemistry of protein synthesis - in which direction is a polymer made?

Which bonds in a protein can rotate and why?

Lecture 2.2: Protein folding. Dr Steve Burston. Protein folding and its importance, illustrated by prion proteins and BSE. Forces which determine protein

structure: hydrogen bonds, hydrophobic effect, etc. Common elements of secondary structure: helix,

sheet and turn Questions:

List the forces which dictate the conformation of a protein molecule.

What is the hydrophobic effect?

What is a hydrogen bond? Give examples?

What are the main secondary structural motifs?

What is the tertiary structure of a protein? Why is it so critical to function?

Lecture 2.3: Clinical applications. Dr Steve Burston. A description of the methods used for isolating and studying proteins: SDS-PAGE, isoelectric focusing, and their clinical applications. Question:

What is the basis of (i) ion exchange chromatography; (ii) SDS-polyacrylamide gel electrophoresis and (iii) isoelectric focusing?

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Lecture 2.4: Enzymes. Dr Steve Burston. An introduction to enzymes, the active site: enzyme inhibition illustrated by ethylene glycol poisoning. The meaning of Km and Vmax controlling the activity of enzymes.

Questions:

State two cases where a drug acts as an enzyme inhibitor.

How would you determine LDH activity in plasma from a patient with a possible heart infarction?

Lecture 2.5: Myoglobin & haemoglobin. Dr Steve Burston. Oxygen saturation curves and sickle cell disease. Questions:

Why does Hb loses oxygen in the tissue but takes up oxygen in the lung?

How does one molecule of 2,3-bisphophoglycerate interacts with Hb?

How would you attempt to discover which haemoglobinopathy accounted for a disease condition?

What is analogous to the interaction of carbon monoxide with Hb, how a competitive inhibitor of an enzyme functions?

Lecture 2.6: Fundamentals of gene expression. Dr Janet Frayne. The flow of genetic information. Genetic material; genomes, genes and chromosomes. Structure and properties of DNA and RNA. Structure of the Watson-Crick double helix. Base pairing. Questions:

What is the overall structure of the DNA double helix?

What do the terms genome, gene and chromosome refer to?

Lecture 2.7: DNA replication. Dr Janet Frayne. DNA polymerases. Semi-conservative DAN replication. DNA synthesis in vitro and in vivo – enzymes and mechanisms Questions:

What is the mechanism of DNA replication?

How does DNA polymerase III replicate both stands of a DNA molecule simultaneously?

Lecture 2.8: Mutations and DNA repair. Dr Janet Frayne. Mutagens, mutations and DNA repair mechanisms. Consequences of defects in repair pathways. Questions:

Why is excessive sunbathing not good for your health?

What is the mechanism for the excision of thymine dimers?

Lecture 2.9: RNA synthesis and DNA transcription in prokaryotes I. Dr Janet Frayne. Structure of RNA, types of RNA, chemistry of RNA synthesis, promoters. Questions:

What are the three classes of RNA and their function?

What is a promoter?

Lecture 2.10: RNA synthesis and DNA transcription in prokaryotes II. Dr Janet Frayne. RNA polymerase, mechanism of DNA transcription Inhibitors of transcription. Questions:

The process of RNA transcription is …?

How do different antibiotics inhibit transcription?

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Lecture 2.11: Biological membranes. Dr Kelly Moule. Localisation and function in cells. The components of membranes. Liposomes. The fluid mosaic model of membrane structure. Importance of cholesterol. Integral and peripheral membrane proteins. Types of membrane proteins – transporters, enzymes, structural proteins, receptors, etc. Glycoproteins. General structure of integral membrane proteins – the transmembrane helix. Lipid and protein mobility within membranes. Questions:

Write out the structure of lecithin and explain the relationship between its physical and chemical properties and its role in membrane structure.

Outline the structure of a named integral membrane protein.

Lecture 2.12: Transport of solutes across membranes. Dr Kelly Moule. Simple diffusion, facilitated diffusion and active transport. Transport mechanisms. The GLUT family of passive glucose transporters. The Na+/K+ ATPase as an example of a primary active transporter. Questions:

How is it possible to distinguish between simple diffusion and carrier-mediated transport?

Explain the action of cardiac glycosides.

Lecture 2.13: Transporter proteins and ion channels. Dr Kelly Moule. Mechanisms for glucose transport into epithelial cells. Amino acid and peptide transporters. The mechanism of ion channels. Cystic fibrosis (CFTR), nAChR and myasthenia gravis. Questions:

Explain how glucose is taken up from the gut.

What is the molecular basis of cystic fibrosis and how is it diagnosed?

Outline the structure and function of the nAChR.

Lecture 2.14: Introduction to metabolism I. Dr Kelly Moule. Overview of metabolism. Definition of anabolism and catabolism. Design and control of metabolism. Basic bioenergetics and the concept of free energy. Structure and properties of ATP. Structure and properties of NADH, FADH2 and NADPH. NADH oxidation as the driving force for ATP synthesis. The role of major coenzymes. Questions:

How can ATP be used to drive an energetically unfavourable reaction in the cell?

Understand substrate level phosphorylation.

Understand the basic reaction catalysed by dehydrogenase enzymes and the role of reducing equivalents in reactions of this type.

Lecture 2.15: Introduction to metabolism II. Dr Kelly Moule. Overview of inter-relationships between carbohydrate, fat and protein metabolism. Organ specialisation. Overview of fats and fat metabolism. Acetyl-CoA as a common metabolic intermediate. Questions:

Outline the main mechanisms of control of metabolic pathways.

Summarise the main metabolic roles of muscle, liver, adipose tissue and brain.

Outline the central role of acetyl-CoA in metabolism.

Lecture 2.16: The oxidation of fatty acids. Dr Kelly Moule. Transport of fatty acids into the mitochondria – the role of carnitine acyltransferase. The oxidation of fatty acids to produce AcCoA by the pathway of beta-oxidation. Defects in fatty acid oxidation. Questions:

Why is carnitine important in fatty acid oxidation?

Why are defects in fatty acid oxidation clinically important?

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How are odd-chain length fatty acids oxidised?

Lecture 2.17: The tricarboxylic acid cycle. Dr Kelly Moule. The tricarboxylic acid cycle as the final common pathway for the oxidation of fuels. The oxidation of AcCoA and formation of CO2 and NADH. Questions:

Why is fluoroacetate a poison?

How many ATP molecules are generated from the oxidation of one acetyl CoA molecule?

How is the TCA cycle regulated in response to energy demand?

Lecture 2.18: Mitochondria and the electron transport chain. Elinor Griffiths. Structure of mitochondria and organisation in cells. Overview of substrate oxidation to produce ATP. The electron transport chain proteins. Oxygen electrode experiments and calculation of P/O ratios; inhibitors of electron transport and ATP synthesis. Questions:

Why can more ATP be synthesised from the oxidation of a molecule of NADH than from a molecule of FADH?

Why is cyanide a particularly effective poison?

Lecture 2.19: Oxidative phosphorylation; brown fat metabolism; mitochondrial DNA. Elinor Griffiths. The chemiosmotic theory of oxidative phosphorylation. The importance of pH gradient and membrane potential. The mitochondrial ATPase – structure and mechanism. Mechanism of action of uncouplers. The mechanism of heat production in brown adipose tissue. The mitochondrial genome and diseases arising form defects in respiratory chain proteins. Questions:

Understand the action of uncouplers. Why are these compounds toxic?

Which proteins are encoded by mitochondrial DNA? PRACTICALS (see Practical Book) All in TL 5.1 Practical 1: pH and buffers (Dr Janet Frayne)

B1 - B8 Wed 16th October, 10:00 A1 - A8 Thur 17th October, 10:00 A9 - A12, B9 - B12 Fri 18th October, 14:00

. Practical 2: Diagnosing Mitochondrial Respiratory Chain Deficiencies (Dr Alice Robson)

B1 - B8 Wed 6th Nov, 10:00 A1 - A8 Thurs 7th Nov, 10:00 A9 - A12, B9 - B12 Fri 8th Nov, 14:00

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ELEMENT 3

FUNCTIONAL ORGANISATION OF THE BODY EXCITABLE MEMBRANES, NERVOUS TRANSMISSION AND MUSCLE MECHANICS

INTRODUCTION TO HOMEOSTATIC MECHANISMS

Element Organiser: Prof Sergey Kasparov, School of Physiology & Pharmacology (Room E3, Medical Sciences Building)

Element Teachers: Prof Sergey Kasparov, Dr Helen Kennedy & Prof Paul Martin, School of Physiology & Pharmacology

OVERVIEW This Element contains 21 Lectures, 3 tutorials and 5 practical classes. Please check your MCBoM timetable on Blackboard for venues of lectures. Physiology Practicals are in TL 3.10 unless otherwise stated. Histology Practicals are in TL 2.2 unless otherwise stated.

TIMETABLE

DATE TIME SESSION

Wed 2nd October 09:00 3.1: Introduction to Physiology. Functional organisation of the body. Homeostasis

Thurs 3rd October 09:00 3.2: Chemistry of the cell

Fri 4th October 09:00 3.3: Physiology of the cell membrane

Mon 7th October 16:00 3.4: Cell & its organelles 1

Thurs 10th October 09:00 Physiology Practical 1: Introduction to Homeostasis (A1 - A8)

Thurs 10th October 11:30 Physiology Practical 1: Introduction to Homeostasis (A9 - A12, B9 - B12)

Thurs 10th October 14:00 Physiology Practical 1: Introduction to Homeostasis (B1 - B8)

Fri 11th October 09:00 3.7 & 3.10: Tissues 1 (Epithelia) and Tissues 2 (Connective Tissue)

Mon 14th October 14:00 3.5: Cell & its organelles 2

Mon 14th October 16:00 3.6: Cell division: mitosis & meiosis, cell as a part of a tissue

Wed 23rd October 10:00 Physiology Tutorial 1 (A2 - A8) .l/

Wed 23rd October 11:00 Physiology Tutorial 1 (B1 - B8)

Thurs 24th October 09:00 3.8: Mechanisms by which chemical messengers control cells Thurs 24th October 10:00 Histology Practical 1: Use of Microscope. Epithelia (A1 - A12)

Thurs 24th October 14:00 Histology Practical 1: Use of Microscope. Epithelia (B1 - B12)

Fri 25th October 09:00 Physiology Tutorial 1 (A9 - A12, B9 - B12)

Fri 25th October 11:00 3.9: The excitable membrane

Mon 28th October 14:00 3.11: Action Potential 1

Mon 28th October 16:00 3.12: Action Potential 2

Thurs 31st October 10:00 Histology Practical 2: Connective Tissue (A1 - A12)

Thurs 31st October 14:00 Histology Practical 2: Connective Tissue (B1 - B12)

Mon 4th November 14:00 3.13 Muscle 1: Structure of muscle

Mon 4th November 15:00 3.14: Muscle 2: Molecular mechanisms of contraction

Mon 11th November 14:00 3.15: Muscle 3: Regulation of muscle contraction

Mon 11th November 15:00 3.16: Muscle 4: Muscle Mechanics

Wed 13th November 10:00 Physiology Tutorial 2 (A1 - A8)

Wed 13th November 11:00 Physiology Tutorial 2 (B1 - B8)

Fri 15th November 09:00 Physiology Tutorial 2 (A9 - A12, B9 - B12)

Mon 18th November 16:00 3.17: Neuromuscular transmission

Wed 20th November 09:00 3.18: Integration in the body: Autonomic nervous system

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Thurs 21st November 10:00 Histology Practical 3: Histology of Nerves and Muscles (A1 - A12)

Thurs 21st November 14:00 Histology Practical 3: Histology of Nerves and Muscles (B1 - B12)

Fri 22nd November 11:00 3.19: Integration in the body: Endocrine system

Mon 25th November 14:00 3.20: Integration of the body: Homeostasis 1

Wed 27th November 10:00 Physiology Tutorial 3 (A1 - A8)

Wed 27th November 11:00 Physiology Tutorial 3 (B1 - B8)

Fri 29th November 09:00 Physiology Tutorial 3 (A9 - A12, B9 - B12)

Fri 29th November 10:00 3.21: Integration of the body: Homeostasis 2

Wed 4th December 10:00 Physiology Practical 2: Muscle-nerve properties in human forearm (A1 - A8)

Thurs 5th December 10:00 Physiology Practical 2: Muscle-nerve properties in human forearm (AB9-12)

Thurs 5th December 14:00 Physiology Practical 2: Muscle-nerve properties in human forearm (B1 - B8)

Thurs 12th December 10:00 Histology Practical 4: Blood (A1 – A12)

Thurs 12th December 14:00 Histology Practical 4: Blood (B1 – B12)

Mon 16th December 14:00 Physiology Revision

Thurs 19th December 10:00 Histology Practical 5: Lymphoid Tissue (A1 – A12)

Thurs 19th December 14:00 Histology Practical 5: Lymphoid Tissue (B1 – B12)

PREREQUISITES Students with A-level Biology:

Knowledge of the basic organisation of the eukaryotic cell and its organelles, and of mitosis and meiosis;

Basic understanding of the main body systems, their overall organisation and function.

Students without A-level Biology: You should make yourself familiar with cell structure and function.

AIMS To understand the basic structure of cells and their normal function. To learn about the fundamental chemical principles of cellular function. To acquire the basic knowledge of the structure of the body and the main mechanisms of integration of body functions. To acquire the initial knowledge of regional anatomy necessary for the clinical examination of patients, and for interpreting images of the body. To learn about the basic principles of cell to cell communication with a special emphasis on neuro-muscular junction. To understand the basic layout of the autonomic nervous system and the endocrine system and to explain their roles in homeostatic regulation of the body.

SPECIFIC OBJECTIVES By the end of the Element, students should:

have developed skills in practical physiology and in the use of the microscope and digital slidebox

appreciate the use of computers for analysing experimental data

recognise variation of experimental measurements, and use simple statistics to find mean and standard deviation

appreciate how the body is organised from the cell to the organism, with some knowledge of scale and terminology (e.g., "homeostasis", "distal versus proximal")

understand the structure of a eukaryotic cell and its organelles

understand the processes involved in maintaining cells in the living state, such as diffusion and osmosis

be able to perform simple calculations relating to the resting potential

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be able to set up a compound light microscope, use it correctly and recognise some basic tissues

understand the structure, functions and distributions of epithelia, connective tissues and muscle and recognise the histology of these tissues at light and electron microscopic level.

understand cell-cell junctions and how glands are formed and classified

understand principles of transmission at the neuromuscular junction (as an example of a synapse)

know mechanics of the muscles and the mechanisms that underlie contraction

be able to list the differences between skeletal, cardiac and smooth muscle

know what an excitable membrane is

understand the ionic basis of the resting and action potential in nerve and muscle fibres in terms of ionic permeability with appropriate reference to the Nernst and Goldman equations

know how an action potential moves (propagates or conducts) down a nerve axon

understand the difference between voltage-gated and ligand-gated channels

know the essential properties of nicotinic acetylcholine receptor, and its role in neuromuscular transmission in health and disease

understand the neuronal basis of the monosynaptic stretch reflex and use it to illustrate the communication of information through action potentials in axons, and transmission at synapses

understand the processes of excitation-contraction coupling and the control of contraction by intracellular free calcium in skeletal muscle and outline how it differs from that in cardiac and smooth muscle

be able to explain the molecular basis of contraction (tension development and shortening) in skeletal muscle, including sliding filaments and cross bridges, and the roles of actin, myosin and troponin

be able to describe the anatomical features and organisation of the autonomic components of the nervous system

be able to draw a diagram to explain the functional layout of the autonomic nervous system and know which transmitters are used by its different components

be able to describe the characteristic end-organ effects of sympathetic and parasympathetic nervous system

be able to draw a diagram to illustrate the hierarchical structure of the endocrine system

know the basic layout of a homeostatic mechanism and be able to illustrate it with several examples

be able to provide examples of homeostatic mechanisms operating in the body at systems level that rely on the autonomic nervous system and the endocrine system

LECTURE SYNOPSES Lecture 3.1: Introduction to Physiology. Functional organisation of the body. Homeostasis. Prof Sergey Kasparov. Cells, tissues, organs and organ systems. Major cell types in the human body. The overall body plan. Body water: intracellular, extracellular, interstitial compartments and plasma. Homeostasis as the central organising principle of the body. Questions:

Can you name the 10 body systems?

What percentage of body water is inside cells?

What is the definition of homeostasis?

Lecture 3.2: Chemistry of the cell (molecular composition of the cell). Prof Sergey Kasparov. Four major classes of biomolecules and their essential features: carbohydrates, lipids, amino acids/proteins and nucleotides and nucleic acids. Basic structure of a plasma membrane. Impact of polarity on the functional properties of biomolecules, lipophylicity and hydrophylicity.

What are the main features of proteins, carbohydrates, phospholipids and nucleic acids and where can they be found in a cell?

What are the sub-units which make up the following polymers: proteins, DNA and glycogen?

Why can some proteins span plasma membrane?

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Lecture 3.3: Physiology of the cell membrane. Prof Sergey Kasparov. Membrane proteins and their roles (channels, transporters, receptors and structural proteins). Why do molecules move across membranes? Basic laws of membrane permeability, passive and active transport. Trans-membrane transport in the cell. Questions:

How do O2 molecules and inorganic ions cross the cell membrane?

What is the electro-chemical driving force?

What does Fick’s law describe?

Dynamics of which transport mechanism(s) would be compatible with the following plot: Lecture 3.4: Cell and its organelles 1. Prof Sergey Kasparov. Light and electron microscopes as tools for studying cells. Basic flow of information in the cell. Nucleus, nucleolus, endoplasmatic reticulum (ER), Golgi complex, ribosomes, mitochondria. Questions:

Do all cells have a nucleus and why is it necessary?

Name two types of the ER and describe their function

Which organelle is the source of energy (ATP) in human cells? Lecture 3.5: Cell and its organelles 2. Prof Sergey Kasparov. Vesicular organelles. Cytoskeleton, microfilaments and microtubules. Cell motility. Questions:

List the sorting processes which occur within the endosome.

What are the roles of microtubules in a cell and why are they polarised?

What is the role of cilia present on the respiratory epithelial cells? Lecture 3.6: Cell division: mitosis & meiosis, cell as a part of a tissue. Prof Sergey Kasparov. Cell turnover in tissues, cell cycle. Stages of cell division (mitosis). Control of cell division. Cell senescence and the concept of stem cells. Questions:

Name the phases of a cell cycle (do not confuse it with stages of cell division!).

What are the stages of mitosis?

What is the role of meiosis and what is the fundamental difference between mitosis and meiosis?

What are the stem cells and where can they be found? Lecture 3.7: TISSUES 1 & 2: Epithelia and Connective Tissue. Prof Paul Martin. Epithelia - types and their distribution of simple vs stratified epithelia; link between structure and function. Questions:

What structural specialisations do epithelia exhibit to increase their protective function?

In what layer of all epithelia do stem cells reside? Connective tissue – types, distribution and functions; cells, ground substance and extracellular fibres of C.T., cartilage and bone; microscopical structure and functional characteristics. Questions:

What cells generate the extracellular matrix of loose connective tissues?

What are the lineage relationships between osteoblasts, osteocytes and osteoclasts?

Concentration

Net

Flux

Concentration

Net

Flux

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Lecture 3.9: Mechanisms by which chemical messengers control cells. Prof Sergey Kasparov. The most important means of inter-cellular communication is chemical signalling. Three main types of receptors (receptor-ion channel, receptor-enzyme and G-protein coupled receptor) will be considered. The idea of second intracellular messenger will be explained. Mechanisms by which chemical signals may control genes will be introduced. Question

List 4 basic mechanisms of inter-cellular communication. Lecture 3.10: The excitable membrane, membrane potential & the properties of nerve cells. Prof Paul Martin. The membrane potential. Ionic basis of the resting membrane potential in nerve and muscle fibres. Selective permeability of the membrane to specific ions (e.g. sodium or potassium). This will include consideration of electrochemical gradients and two important equations: the Nernst equation and the Goldman Constant Field equation. Questions:

The membrane of most cells is most permeable to which cation?

How are the transmembrane concentration gradients of Na and K maintained?

Lecture 3.11 & 3.12: Action Potential 1 & 2. Prof Sergey Kasparov. Ionic basis of an membrane potential. Reversal (equilibrium) potential, Nernst equation. Na/K ATPase.Features of action potential. Na+ and Ca2+ channels. Refractory periods. Saltatory conductance. Demyelinisation diseases. Questions:

What is the dynamics of Na+ and K+ currents during action potential?

What terminates the action potential? Why myelin is so important?

Lecture 3.13: Muscle 1: Structure of muscle. Dr Helen Kennedy Mechanisms of animal movement; classification of muscle; architecture of skeletal cardiac and smooth muscle, molecular structure of the sarcomere and disease Questions:

Describe the organization and components of each of the following structures; myofibrils, muscle fibres and muscle

Draw a sarcomere and label its components. Briefly state the function of each component.

Lecture 3.14: Muscle 2: Molecular mechanisms of muscle contraction. Dr Helen Kennedy The sliding filament mechanism; the cross-bridge cycle, regulation by calcium. Questions:

How do myosin cross-bridges produce the force that causes the thick and thin filaments to slide past each other?

Why do muscles become rigid during rigor mortis?

Lecture 3.15: Muscle 3: Regulation of muscle contraction. Dr Helen Kennedy Excitation-contraction coupling; role of (i) action potential, diseases of motor neurons and neuromuscular junction, (ii) Ca2+ ions, (iii) sarcoplasmic reticulum and disease, and (iv) T tubules in the regulation of muscle contraction, twitches and tetanus. Questions:

List the steps by which Ca2+ regulates the contraction of skeletal muscle fibres.

List the steps involved in skeletal muscle activation and relaxation.

What are the major processes in muscle function that require ATP?

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Lecture 3.16: Muscle 4: Muscle mechanics. Dr Helen Kennedy Muscle contraction; loss and gain of muscle mass; function of different types of skeletal muscle fibres; relationship between force and muscle length in health and disease; comparison of skeletal, cardiac and smooth muscle. Questions:

What effect does increasing the frequency of action potentials in a skeletal muscle fibre have on the force of contraction? Explain the mechanism responsible for this effect.

Understand the relationship between active and passive tension in skeletal muscle. What components of skeletal muscle produce active and passive tension?

You should be able to do the same for cardiac muscle and know it’s importance in cardiac function and disease.

Lecture 3.17 Transmission at the neuro-muscular junction. Prof Sergey Kasparov. Ultrastructure of the NMJ. Ion channels involved in neuro-muscular transmission. Exocytosis of acetylcholine. Miniature and graded end plate potentials. Acetyl-cholinesterase. Questions:

What is BoTox?

Why inhibition of acetyl cholinesterase can both, enhance and inhibit neuromuscular transmission.

Lecture 3.18: Integration in the body: the autonomic nervous system. Prof Sergey Kasparov. Functional layout of the autonomic nervous system (ANS): two major divisions of the ANS, the sympathetic and parasympathetic nervous systems, the autonomic afferents. Transmitters used in different synapses of the ANS. Characteristic actions of the sympathetic NS and parasympathetic NS in ‘fight or flight’ vs. ‘rest & digest’ situations. Examples of how the ANS may act as a target for a medical intervention. Questions:

List the major anatomical and pharmacological differences between the organisation of the sympathetic and the parasympathetic nervous systems.

List the physiological actions of the sympathetic and parasympathetic nervous systems (effects on eye, heart, bronchi, blood vessels, GI tract).

Lecture 3.19: Integration in the body: the endocrine system. Prof Sergey Kasparov. Nature of a hormone as a chemical messenger, comparison between a neurotransmitter and a hormone, chemistry of the hormones. The most important endocrine glands and their hormones. Tissue targets and hormone receptors. Role of hypothalamus in control of the endocrine system. Factors affecting concentration of hormones in the blood, negative feedbacks. Examples of endocrine diseases. Questions:

List the similarities and dissimilarities between neurotransmitters and hormones.

What is the role of anterior pituitary?

Give examples of hormones of peptide and steroid structure and their main effects. Lectures 3.20 & 3.21: Integration in the body: Homeostasis 1& 2. Prof Sergey Kasparov What is homeostasis? General principles of the operation of homeostatic mechanisms and the application of cybernetic terminology: closed cybernetic system: sensor, negative feedback, communication, controller, setpoint and controlled output with examples of what these terms mean in biological systems. Roles of the autonomic nervous system and the endocrine system in homeostatic processes. Short and long feedback loops. Examples of homeostatic systems which control blood gases, blood pressure, blood glucose, body temperature etc. Questions:

What is homeostasis and how is this important in living organisms, and what are the principles of operation of homeostatic mechanisms using the language of a closed cybernetic system: sensor, negative feedback, communication, set point, controller.

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Annotate a diagram which illustrates the components and principles of: a generalised negative feedback loop involved in whole body homeostasis homeostatic mechanisms that control blood pressure homeostatic mechanisms that control blood glucose

PRACTICALS (see practical book)

Physiology Practical 1: Introduction to Homeostasis. Physiology Practical 2: Muscle-nerve Properties in the Human Forearm.

Histology Practical 1: Part 1: Use of the Microscope. Part 2: Epithelia. Histology Practical 2: Connective Tissue. Histology Practical 3: Histology of Nerves and Muscles.

PHYSIOLOGY REVISION SESSION Monday 16th December This will be a combination of a computer assisted self-assessment and a tutorial where your physiology lecturers will also be present. You will have an opportunity to ask questions about the issues you did not understand during the lectures. Please do look through your lecture notes before you come to this session and perhaps have a couple of questions ready. A1 - A4 14:00 – 15:00 in TL 2.2 A5 - A8 14:00 – 15:00 in TL 4.14 B1 - B4 15:00 – 16:00 in TL 2.2 B5 - B8 15:00 – 16:00 in TL 4.14 A9 - A12 16:00 – 17:00 in TL 2.2 B9 - B12 16:00 – 17:00 in TL 4.14

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ELEMENT 4

HOMEOSTATIC MECHANISMS & METABOLIC HOMEOSTASIS An Overview of Tissue Interactions in Metabolism

ORGANISATION

Element Organiser: Dr Elinor Griffiths, School of Biochemistry, Medical Sciences Building.

Element Teachers: Dr Elinor Griffiths, Prof Harry Mellor & Dr Kelly Moule, School of Biochemistry, Medical Sciences Building.

OVERVIEW This Element contains 15 lectures and 1 practical. Please check your MCBoM timetable on Blackboard for venues of lectures. The practical is held in TL 5.1 and is taken by Dr Kelly Moule.

TIMETABLE

DATE TIME SESSION LECTURER

Thurs 7th November 09:00 4.1: Carbohydrate Metabolism I Prof Harry Mellor

Fri 8th November 11:00 4.2: Carbohydrate Metabolism II Prof Harry Mellor

Fri 8th November 12:00 4.3: Carbohydrate Metabolism III Prof Harry Mellor

Mon 11th November 16:00 4.4: Carbohydrate Metabolism IV Prof Harry Mellor

Wed 13th November 09:00 4.5: Carbohydrate Metabolism V Prof Harry Mellor

Mon 18th November 14:00 4.6: Metabolism of Andipose Tissue Dr Kelly Moule

Mon 18th November 15:00 4.7: Metabolism of Liver I Dr Kelly Moule

Thurs 21st Nov 09:00 4.8: Metabolism of Liver II Dr Kelly Moule

Fri 22nd November 12:00 4.9: Hormonal regulation of tissue metabolism Dr E Griffiths

Mon 25th November 15:00 4.10: Molecular Basis of Glucagon & Adrenaline Action Dr E Griffiths

Mon 25th November 16:00 4.11: Metabolic Effects of Glucagon & Adrenaline Dr E Griffiths

Wed 27th November 09:00 4.12: Regulation of Hormone Secretion Dr E Griffiths

Fri 29th November 11:00 4.13: Glucocorticoid Action Dr E Griffiths

Fri 29th November 12:00 4.14: Insulin: Signalling Pathways & Metabolic Effects Dr E Griffiths

Wed 4th December 10:00 Biochemistry Practical 3 (B1 – B8) Dr K Moule

Thurs 5th December 09:00 4.15: Metabolic Integration by Hormones, and Diabetes Dr E Griffiths

Thurs 5th December 10:00 Biochemistry Practical 3 (A1 – A8) Dr K Moule

Fri 6th December 14:00 Biochemistry Practical 3 (A9 – A12, B9 – B12) Dr K Moule

AIMS

The aims of Element 4 are that students should gain an understanding of the biochemical principles underlying:

the principle metabolic activities of muscle, adipose tissue, liver and the central nervous system how the metabolic activity of these tissues changes to meet the physiological needs of the whole body

during feeding and fasting, exercise and rest the role of intrinsic regulation by metabolites and of extrinsic regulation by the hormones glucagon, insulin,

the catecholamines and glucocorticoids in these changes.

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PRE-REQUISITES Before starting this Element students should revise the material presented in Element 2.

OBJECTIVES

By the end of Element 4 the student should be able to compare the whole-body metabolic patterns in feeding and fasting, exercise and rest, explain the principle metabolic roles of muscle, adipose tissue, liver and central nervous system in these conditions, and explain the mechanisms by which they are integrated. More specifically, the student should be able to:

understand the pathway of glycolysis

know the differences between biosynthesis of glycogen and glycogen breakdown and why separate pathways are necessary

know the principles of control of metabolic pathways and the intracellular integration of metabolism, including long and short-term, intrinsic and extrinsic mechanisms

know the major metabolic pathways in muscle and how they interact to maintain ATP concentration.

understand the importance of oxygen availability on the metabolism of muscle cells

understand how the oxidation of fatty acids decreases glucose metabolism in muscle

know the terms respiratory quotient and P/O ratio, and calculate these values for major metabolic fuels

understand the metabolism of white fat cells in outline and aspects of its regulation

know the metabolism of carbohydrate in liver and its importance in glucose homeostasis

know the pathway of gluconeogenesis from lactate alanine and glycerol in liver and its control

understand the effect of fatty acid provision on the formation of ketone bodies and gluconeogenesis

be able to list the main hormones that regulate metabolism, and how levels of such hormones are measured in plasma or urine.

understand the changes in plasma concentrations of glucose and hormones in fasting and exercise

be able to list the mechanisms regulating the secretion of insulin, glucagon, adrenaline and glucocorticoids; compare and contrast their secretory pathways

know the signal transduction pathways used by glucagon, adrenaline, insulin and glucocorticoids.

explain how these signalling pathways affect metabolism in liver, adipose tissue, heart and skeletal muscle

be able to list diseases arising from defects in hormones synthesis, secretion or action, and describe the metabolic abnormalities that occur in these diseases (diabetes, Addison’s disease and Cushing’s syndrome).

know the changes in hormone levels and circulating metabolites that occur during feeding and fasting, and how these act to integrate metabolism between different tissues.

LECTURE SYNOPSES Lecture 4.1: Carbohydrate metabolism 1. Professor Harry Mellor. Dietary sugars and carbohydrates. Digestion of carbohydrate in the mouth and gut. The biochemical basis of lactose intolerance. Normal blood glucose levels. Storage of glucose in the body as glycogen. Questions:

Cows can live on grass, we can live on potatoes – discuss.

Why is yoghurt well-tolerated by people with lactose intolerance, but whole milk less so?

What properties of the glycogen molecule make it a good way to store carbohydrate?

Lecture 4.2: Carbohydrate metabolism 2. Professor Harry Mellor. Glycogen breakdown and glucose homeostasis. Diseases of the glycogen storage pathway. Transport of glucose into cells. An outline of the glycolysis pathway. Questions:

What are the different severities of different glycogen storage diseases with reference to the enzymes involved?

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Why are there different glucose transporters?

Lecture 4.3: Carbohydrate metabolism 3. Professor Harry Mellor. The steps of the glycolysis pathway. Glycolysis is an anaerobic route to ATP generation. The production of lactate in anaerobic cells. Clinical consequences of lactic acidosis. Transport of pyruvate and NADH into the mitochondria. Vitamin B1 and Wernicke’s syndrome. The clinical importance of vitamin B1 in the treatment of alcoholic patients. Questions:

How does the pathway of glycolysis generate ATP in anaerobic conditions?

Why might a glucose drip be dangerous for an alcoholic patient?

Lecture 4.4: Carbohydrate metabolism 4. Professor Harry Mellor. Anerobic versus aerobic exercise. Muscle fibers specialized for different metabolisms. Fuel sources for aerobic and anerobic excersise. The function of creatine in exercising muscle. AMP as a low energy signal. Questions:

What happens to NADH generated by glyceraldehyde dehydrogenase in muscle under (i) anaerobic (ii) aerobic conditions?

Compare the efficiency of muscle metabolism in a sprint with a marathon.

Lecture 4.5: Carbohydrate metabolism 5. Professor Harry Mellor. The regulation of metabolic pathways – basic principles. Intrinsic and extrinsic regulation. Regulation of pathways of carbohydrate metabolism in exercise. Tumours as anaerobic tissues. The metabolic burden of tumours to cancer patients. Use of FDG-PET as a tool to detect tumours and micrometastasis. Questions:

How are metabolic pathways regulated using glycolysis as an example?

Why does anaerobic respiration in tumour cells lead to patient weight loss?

Lecture 4.6: Metabolism of Adipose Tissue. Dr Kelly Moule. Summary of white adipose tissue metabolism. Pathways of fatty acid synthesis in outline summarising the location in cytoplasm, sources of acetyl-CoA and NADPH, and regulation, synthesis and breakdown of triacylglycerol. Questions:

What is the pathway for the conversion of glucose into triacylglycerol?

What is the citrate shuttle? Explain its role.

How are the rates of fatty acid synthesis and triacylglyceride breakdown (lipolysis) regulated?

Lecture 4.7: Metabolism of Liver 1. Dr Kelly Moule. An outline of the role of the liver in glucose homeostasis. The Cori cycle. The pathway of gluconeogenesis from alanine, lactate and glycerol and its control. Questions:

How do the kinetic properties of glucokinase differ from those of hexokinase?

What are the major substrates of liver gluconeogenesis and when are they important?

Give the reactions in the main pathway of gluconeogenesis which differ from those in glycolysis.

How is the reciprocal regulation of gluconeogenesis and glycolysis in the liver brought about by a combination of long-term and acute mechanisms?

Lecture 4.8: Metabolism of Liver 2. Dr Kelly Moule. Overview of the role of the liver in lipid metabolism. Ketone body formation and their utilisation by other tissues. Questions:

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What are ketone bodies and how are they produced?

Why fatty acids cannot be converted to glucose?

How is the rate of ketone body production controlled?

Lecture 4.9: Role of Hormones in Coordinating Tissue Metabolism. Dr Elinor Griffiths. Principles of signal transduction - receptors, second messengers and protein kinases. Plasma concentrations of glucose, and hormones (glucagon and insulin) during fasting and feeding. Questions:

What are hormones? What are the differences between endocrine, paracrine and autocrine factors?

What are the steps you would take in order to set up a routine clinical assay to measure the concentration of a protein hormone in blood?

How would the plasma concentrations of insulin and glucagon in blood change in a normal person ingesting glucose after an overnight fast? Outline the importance of the changes.

Lecture 4.10: Molecular Basis of Glucagon & Adrenaline Action. Dr Elinor Griffiths. Seven transmembrane-domain (7TMD) receptors, guanine nucleotide-binding proteins (G-proteins), adenylate cyclase and cyclic AMP (cAMP); protein kinases. Cytoplasmic free calcium concentration, phospholipase C, IP3 and diacylglycerol (DAG). G-proteins: toxins and mutations. Questions:

In some cells, adrenaline increases the cytoplasmic cyclic AMP concentration ([cAMP]i) whereas in other

cells it decreases [cAMP]i. Explain how these effects are produced.

What is the reaction catalysed by phospholipase C? How could ingestion of lithium carbonate decrease the synthesis of inositol-containing phospholipids in brain? How may this be related to the clinical application of lithium chloride?

How do cholera toxin and pertussis toxin affect the cytoplasmic concentration of cyclic AMP?

Lecture 4.11: Metabolic Effects of Glucagon & Adrenaline. Dr Elinor Griffiths. Stimulation of gluconeogenesis and glycogenolysis in liver; lipolysis in adipose tissue; glycogenolysis in muscle. Questions:

What is cyclic 3'5'-AMP (cAMP)? How does it differ from 5'-AMP? How do these compounds alter glycogen breakdown?

How does adrenaline increase lipolysis in adipose tissue?

Lecture 4.12: Regulation of Hormone Secretion. Dr Elinor Griffiths. Secretory pathways for the protein hormones insulin and glucagon; regulation of secretion by glucose. Adrenaline and glucocorticoid synthesis and secretion. Questions:

What is the process of insulin synthesis and storage in the pancreatic ß-cell? How is the secretion of insulin regulated?

How is adrenaline and cortisol synthesized by the adrenal medulla and cortex respectively?

Lecture 4.13: Glucocorticoid Action. Dr Elinor Griffiths. Steroid receptors and the regulation of gene transcription. Effects of glucocorticoids on metabolism. Question:

What is the mechanism by which cortisol and corticosterone affect liver metabolism? Why could the absence of these hormones lead to severe hypoglycaemia on fasting?

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Lecture 4.14: Insulin: Signalling Pathways & Metabolic Effects. Dr Elinor Griffiths. The insulin receptor tyrosine kinase and signalling pathways. Long-term versus short-term effects of insulin receptor activation. Stimulation of glucose uptake in adipose tissue and muscle. Stimulation of synthesis of glycogen, fatty acids and triglycerides. Questions:

How may occupancy of the insulin receptor lead to the activation of glucokinase gene expression?

How does insulin increase glucose uptake into muscle and adipose tissue?

What are the mechanisms by which insulin affects protein phosphorylation in the appropriate target cells? .

Lecture 4.15: Metabolic Integration by Hormones, & Diabetes. Dr Elinor Griffiths. Metabolism during fasting and feeding. Metabolic disturbances in type-I and type-II diabetes. Questions:

What is the relationship between glucose and fatty acid metabolism in muscle, adipose tissue and liver in fasting and feeding?

Why can’t type-I diabetes be treated with sulphonylureas?

What do you understand by the term “insulin resistance”?

PRACTICAL (See Practical Book) Practical 3: The Diagnosis of Diabetes Mellitus

Weds 4th December, 10:00: B1 – B8 Thurs 5th December, 10:00: A1 – A8 Fri 6th December, 14:00: A9 – A12, B9 – B12

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ELEMENT 5

INTERVENTION IN HOMEOSTASIS An Introduction to Pharmacology & Therapeutics

ELEMENT OVERVIEW This Element contains 13 Lectures 1 tutorial and 2 practicals. Please check your MCBoM timetable on Blackboard for venues of lectures. Practicals are in TL 4.14. Element Organiser: Prof Graeme Henderson, School of Physiology & Pharmacology, School of Medical Sciences Element Teachers: Prof. Neil V. Marrion, School of Physiology & Pharmacology.

Dr James Hodge, School of Physiology & Pharmacology Dr Maria Usowicz, School of Physiology & Pharmacology.

TIMETABLE

DATE TIME SESSION

Mon 27th January 11:00 5.1: Mechanisms of Drug Action I

Mon 27th January 12:00 5.2: Mechanisms of Drug Action II

Mon 27th January 14:00 5.3: Mechanisms of Drug Action III

Mon 3rd February 10:00 5.4: Mechanisms of Drug Action IV

Tues 4th February 12:00 5.5: Enzymes as Drug Targets

Wed 5th February 11:00 5.6: Pharmacology of Parasympathetic Nervous System I

Wed 5th February 12:00 5.7: Pharmacology of Parasympathetic Nervous System II

Mon 10th February 10:00 5.8: Pharmacology of Parasympathetic Nervous System III

Thurs 13th February 09:00 5.9: Pharmacology of the Neuromuscular Junction I

Mon 17th February 10:00 5.10: Pharmacology of the Neuromuscular Junction II

Wed 19th February 10:00 Pharmacology Practical 1 (B1 - B8)

Wed 19th February 11:00 Pharmacology Tutorial (A1 – A4)

Wed 19th February 12:00 Pharmacology Tutorial (A5 – A8)

Thurs 20th February 09:00 5.11: Pharmacology of Sympathetic Nervous System I

Thurs 20th February 10:00 Pharmacology Practical 1 (A1 – A8)

Thurs 20th February 10:00 Pharmacology Tutorial (A9 – A12)

Thurs 20th February 11:00 Pharmacology Tutorial (B9 – B12)

Thurs 20th February 14:00 Pharmacology Practical 1 (A9 - A12, B9 - B12)



Mon 24th February 10:00 5.12: Pharmacology of Sympathetic Nervous System II

Mon 24th February 11:00 5.13: Pharmacology of Sympathetic Nervous System III

Thurs 27th February 10:00 Pharmacology Practical 2 (A1 - A8) + STAN sessions 14:00

Thurs 27th February 14:00 Pharmacology Practical 2 (B1 - B8) + STAN sessions 6th Mar

Thurs 6th March 10:00 Pharmacology Practical 2 (A9 – A12, B9 – B12) + STAN sessions 10:00

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PREREQUISITES Before starting the Element, students should already have an understanding:

Fundamental properties of eukaryotic membrane structure and function The structural organisation of the peripheral nervous system, smooth and striated muscle and the

synapse.

AIMS The aims of Element 5 are to ensure that students:

understand the basic qualitative and quantitative properties of cell receptors;

appreciate the ways in which chemical messengers, such as peripheral neurotransmitters, interact with receptors in order to influence the activity of cells;

understand the pharmacological mechanisms by which drugs can modify the action of chemical messengers, or influence the activity of cellular metabolic events.

are able to give named examples of prototypic drugs acting upon particular receptors/receptor subtypes or upon enzymes

appreciate the pharmacological basis for therapeutic intervention, providing examples from the autonomic and somatic nervous systems.

OBJECTIVES By the end of this Element, students should:

know the terms receptor specificity, agonists, antagonists, partial agonists and receptor reserve. be able to distinguish between competitive and non-competitive drug- receptor interactions. understand the concept of receptor families and outline the receptor-effector mechanisms for receptors

linked to ion channels and G-proteins. understand the importance of second messenger systems including cyclic nucleotides, inositol 1,4,5-

trisphosphate (IP3) and calcium in relation to drug action.

understand the adaptive changes that may occur in receptor populations with acute and chronic drug exposure.

know the pharmacological organisation of the autonomic nervous system (ANS) and somatic nervous systems in relation to their anatomical divisions.

be able to compare and contrast neurotransmitter synthesis, storage, release and inactivation at cholinergic and adrenergic synapses and describe the mechanisms that exert control on the release of acetylcholine and noradrenaline in the ANS.

list the major classes of drugs influencing ANS function. be able to list reasons for intervening pharmacologically in ANS function. be able to give examples of clinically-important drugs affecting the ANS (e.g. cardiovascular and

airways control) and explain their mechanisms of action. know the steps involved in neurotransmission at the neuromuscular junction and the pharmacological

means and therapeutic consequences of modifying function.

LECTURE SYNOPSES

SITES OF DRUG ACTION (Prof Neil V Marrion)

Lecture 5.1: Cellular receptors for chemical messengers. Receptor superfamilies. Overview of ligand-gated and G-protein -coupled receptors as targets for drug action. Questions:

What is a receptor? Can an enzyme be regarded as a receptor? If not, explain why.

How does binding of a small molecule (e.g. drug) to a receptor result in a biological response?

Lecture 5.2: Cell surface receptors as pharmacological and therapeutic targets. Receptor activation - agonist and antagonist actions. Introduction to quantitative aspects of drug-receptor interactions. Questions:

What simple equation represents the reaction of a drug with its receptor?

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On the basis of this equation and applying the Law of Mass Action, define the equilibrium dissociation constant KD.

What equation gives the proportion of receptors occupied, and how is this related to the drug concentration and the KD?

What is meant by drug affinity?

Lecture 5.3: The dose (concentration)-response relationship. Concepts of potency and efficacy; receptor reserve and partial agonism. Questions:

What is meant by efficacy?

What is meant by agonist potency?

What is meant by 'spare receptors' (receptor reserve)

What is the difference between a full agonist and a partial agonist? What is the relationship between response and occupancy for a full agonist and for a partial agonist?

Lecture 5.4: Competitive and non-competitive antagonism. Regulation of receptor function. Receptor desensitisation and sensitisation. Questions:

What is the difference between physiological antagonism and competitive antagonism?

What is meant by the term 'dose-ratio'? How is it related to concentration of antagonist?

What processes might underlie the loss of response to a drug? Lecture 5.5: Enzymes as Drug Targets. Drugs which act as enzyme inhibitors. Measuring enzyme activity. Different types of inhibition. Target enzymes, including cyclo-oxygenase (COX), monoamine oxidase (MAO), acetylcholinesterase (AChE), and angiotensin converting enzyme (ACE). Questions:

What is the mechanism of action of aspirin?

Why do some anti-inflammatory drugs cause bleeding?

How can enzymes recover from irreversible inhibition?

Why should patients taking MAO inhibitors avoid cheese?

PHARMACOLOGICAL INTERVENTION IN NERVE-NERVE AND NERVE-MUSCLE COMMUNICATION (Dr James Hodge)

Lecture 5.6: Organisation of the ANS and somatic nervous systems in relation to their neurotransmitters and receptors. Target sites for drug action. Synthesis, storage and release of acetylcholine and physiological control of cholinergic function. Questions:

Which part of the peripheral nervous system is not part of the autonomic nervous system?

What is the transmitter at each of the following sites? skeletal muscle; preganglionic sympathetic nerve terminals; postganglionic sympathetic nerve terminals; preganglionic parasympathetic nerve terminals; postganglionic parasympathetic nerve terminals

Which tissues are innervated by sympathetic but not by parasympathetic nerves?

Which tissues are innervated by parasympathetic but not by sympathetic nerves?

What would be the effect on the pupils of the eyes and skin of the face, if the sympathetic chain on one side of the neck was irreparably damaged?

Lecture 5.7: Properties of ganglionic (nicotinic) and postganglionic parasympathetic (muscarinic) receptors. Agonist and antagonist actions. Questions:

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What transduction mechanisms mediate the cellular effects of acetylcholine (ACh) on M1, M2, and M3 receptors?

Where are the following enzymes found and what reactions do they catalyse: acetylcholinesterase; choline acetyltransferase; butyrylcholinesterase?

Lecture 5.8: Major classes of drugs affecting parasympathetic function. Clinical examples illustrating the pharmacological principles in modifying parasympathetic function. Questions:

What is the main clinical use of the ability of certain drugs to stimulate muscarinic receptors? Which drug(s) is used? How does it act?

What are the main peripheral actions of atropine?

Which muscarinic receptor antagonists are used in the eye? What are the indications for their use?

Lecture 5.9: Dr Maria Usowicz: Properties of skeletal muscle nicotinic receptors. Block of neuromuscular transmission by competitive antagonists. Clinical uses of drugs. Questions:

What is meant by 'depolarisation block' at the neuromuscular junction? How does this differ from the non-depolarising block that occurs with certain drugs?

What is the duration of the neuromuscular block produced by the following drugs: suxamethonium, tubocurarine and atracurium? How are the actions of these agents terminated?

Lecture 5.10: Dr Maria Usowicz: Mechanisms of action and uses of depolarising neuromuscular blockers and anticholinesterases. Myasthenia Gravis. Questions:

What are the steps involved in the hydrolysis of ACh by acetylcholinesterase?

How do the interactions of neostigmine, dyflos (DFP; diisopropylfluorophosphonate) and ACh with acetylcholinesterase differ?

What would be the effects of ingestion of an organophosphate insecticide (eg parathion)?

What are the three main clinical uses of anticholinesterase agents?

Lecture 5.11: Dr Maria Usowicz: Overview of adrenergic pharmacology, including the manipulation of synthesis, storage and release of noradrenaline and adrenaline. Questions:

What are the main steps in noradrenaline biosynthesis?

Which drugs interfere with noradrenaline biosynthesis? Are they clinically useful, and if so what for?

How is noradrenaline stored in the nerve terminal? How is it released? What receptors are involved in regulating this release?

What drugs can decrease noradrenaline release? Are they clinically useful, and if so what for?

Lecture 5.12: Dr Maria Usowicz: Concept of - and -adrenoreceptors. Effects of stimulation and the potential clinical uses of selective agonists - direct and indirectly-acting sympathomimetics. Questions:

Give examples of drugs acting as agonists mainly on the receptors specified:

(i) 1 (ii) 2 (iii) 1/ 2 (iv) 1 (v) 2 (vi) 1/ 2 (vii) /

Give examples of drugs acting as antagonists mainly on the receptors indicated in above

In an anaesthetised animal, whose blood pressure is being recorded, injection of tyramine causes a rise in blood pressure. If the injection is repeated every 10 minutes or so, the response gradually fades away. What is the reason for the rise in blood pressure initially? Why is it attenuated on repeated administration? How could the response be restored?

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Lecture 5.13: Dr Maria Usowicz: Effect and clinical applications of - and -adrenoreceptor antagonists. Questions:

What 2 actions are clinically useful? Give an example of a drug with both 1 and 2 agonist activity. If the

drug is being used therapeutically for its 2 effects, will the 1effects be useful or unwanted? Why?

For what condition(s) is injection of a drug acting on adrenoceptors an acute, life-saving measure?

What are the main therapeutic uses of -adrenoceptor antagonists?

PRACTICALS: In the Pharmacology Teaching Laboratory (TL 4.14), School of Medical Sciences. Pharmacology 1: Agonism and Antagonism Weds 19th February, 10:00 B1 – B8 Thurs 20th February, 10:00 A1 – A8 Fri 28th February, 14:00 A9 – A12, B9 – B12 Pharmacology 2: Practical Investigations into noradrenergic and cholinergic pharmacology Thurs 27th February, 10:00 A1 - A8 Thurs 27th February, 14:00 B1 - B8 Thurs 6th March, 10:00 A9 - A12, B9 - B12

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ELEMENT 6

AN INTRODUCTION TO GENETICS, GENETIC DISEASES & MOLECULAR GENETICS

OVERVIEW

Element Organiser: Dr Janet Frayne, School of Biochemistry, Medical Sciences Building

This Element contains 14 lectures. Please check your MCBoM timetable on Blackboard for venues of lectures. The practicals are held in TL 5.1. The lectures are subdivided into two sections:

6A: Molecular Genetics: 8 lectures & 1 practical 6B: Basic Genetics: 6 lectures

Element Teachers: Element 6A: Dr Janet Frayne, School of Biochemistry, Medical Sciences Building Element 6B: Dr. Kathleen Gillespie, Diabetes and Metabolism Unit, Southmead Hospital.

TIMETABLE:

DATE TIME SESSION

Tues 28th January 09:00 6A: 6.1: tRNA & the Genetic Code

Tues 28th January 10:00 6A: 6.2: Protein Synthesis 1

Wed 29th January 10:00 Biochemistry Practical 4 (B1 - B8)

Thurs 30th January 10:00 Biochemistry Practical 4 (A1 - A8)

Fri 31st January 09:00 6A: 6.3: Protein Synthesis 2: Antibiotic Inhibitors

Fri 31st January 14:00 Biochemistry Practical 4 (A9 - A12, B9 - B12)

Mon 10th February 11:00 6A: 6.4: Eukaryotic Transcription & Regulation

Tues 11th February 10:00 6A: 6.5: Human Genome, Mutations & Genetic Disease

Tues 11th February 11:00 6A: 6.6: Recombinant DNA Technology 1

Fri 14th February 09:00 6A: 6.7: Recombinant DNA Technology 2

Fri 14th February 10:00 6A: 6.8: Genomes, Transcriptomes & Proteomes

Mon 17th February 14:00 6B: 6.9: Mitosis & Meiosis: Karyotypes

Mon 17th February 15:00 6B: 6.10: Abnormalities of Chromosomes

Fri 21st February 11:00 6B: 6.11: Introduction to Single Gene Disorders

Mon 24th February 12:00 6B: 6.12: Sex Chromosomes & X-Linked Inheritance

Mon 24th February 14:00 6B: 6.13: Multifactorial (Polygenic) Inheritance

Mon 24th February 15:00 Biochemistry Data Handling Workshop (90 mins)

Thurs 27th February 09:00 6B: 6.14: Population Genetics

AIMS

The aim of this Element is that students should gain an understanding of:

the molecular basis of genetics; the relationship between gene expression, nucleic acids and protein synthesis

the composition of the human genome and the relationship between mutations and disease

recombinant DNA technology and its application to molecular medicine

the fundamental processes of inheritance and mutation and how these affect patients individually and in discrete populations

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the three broad categories of genetic diseases

the principles of gene and chromosome analysis.

PRE-REQUISITES

You should be familiar with the material presented in Element 2. Basic biology and biochemistry, including: the organisation of cells; proteins and enzymes; nucleic acid structure, DNA replication and gene expression.

OBJECTIVES

By the end of Section 6A, the students should:

know the principles of the genetic code and describe in general terms the processes of transcription and translation in gene expression

understand the basic mechanism for protein synthesis; the role of tRNA as an adaptor and the function of ribosomes on mRNA

be able to list differences in the mechanism of protein synthesis between prokaryotic and eukaryotic cells

know how the differences in protein synthesis between eukaryotes and prokaryotes can be exploited clinically by the selective action of certain antibiotics

understand the general strategies for gene expression in mammalian cells

be able to list mechanisms for regulating gene expression in higher eukaryotes

be able to list the composition of the human genome in relation to genes and extragenic DNA

understand the clinical importance of SNPs and explain how mutations in both coding and non-coding regions of the genome can lead to genetic disease

understand the concept of epigenetics and its importance in genetic disease and cancer

know the basic tools used to study DNA, gene expression and gene mutations including restriction enzymes, cloning vectors, DNA ligase, cDNA,

know why there is a need to clone both normal and mutant genes

understand why E. coli is used in molecular genetics, particularly its plasmids and the consequences for antibiotic resistance

know some basic technologies used to study DNA and gene expression including DNA cloning, Southern blots, the polymerase chain reaction, DNA microarrays, 2D protein gels

know how the above technologies can be applied to molecular medicine

understand the basic principles of gene therapy and outline examples of the viral vectors used, and the difficulties and problems associated with the use of gene therapy strategies to date

understand the difference between the study of genomes, transcriptomes and proteomes and how such studies can be applied to an increased understanding of disease.

By the end of the lectures in Section 6B, the students should:

know the organisation of genetic information into chromosomes

be able to list reasons for undertaking karyotypes

understand the methods used in preparation of karyotypes

be familiar with nomenclature for describing chromosomes and their banding pattern, as well as the chromosomal complement of an individual.

know mitosis and meiosis, and understand the special significance of meiosis

understand numerical and structural chromosomal disorders and be able to give examples

know the chromosomal basis of sex determination and understand X-inactivation

be able to distinguish between a gene and an allele, and between genotype and phenotype

know symbols and annotation used to construct a pedigree give examples of dominant, recessive and X-linked disorders and understand their inheritance patterns.

understand the concepts of genetic recombination and linkage disequilibrium (LD)

understand multifactorial inheritance

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understand how LD has lead to recent developments in the identification of genes underlying multifactorial disorders

understand how environmental factors modulate the expression of multifactorial disorders

understand the concept of Hardy-Weinberg equilibrium and the factors which can disturb it

be able to use the Hardy-Weinberg law in simple calculations of carrier frequency for autosomal recessive disorders

understand principles concerning the impact of altering survival rates on gene frequency, and possible clinical implications.

LECTURE SYNOPSES

6A: Lecture 6.1: tRNA & the Genetic Code. Dr Jan Frayne. The genetic code, the role and function of tRNA molecules and the ‘wobble hypothesis’. Questions:

What is meant by the terms universal, degenerate and synonyms in relation to the genetic code?

How is an amino acid attached to a tRNA molecule and activated?

What is the ‘wobble hypothesis’? 6A: Lectures 6.2 & 6.3: Protein Synthesis 1 & 2. Dr Jan Frayne. The structure of prokaryotic and eukaryotic ribosomes. mRNA translation: initiation, elongation and termination of protein synthesis. Similarities and differences between prokaryotic and eukaryotic cells. Post translation modification of proteins. Antibiotic inhibitors of protein synthesis. Questions:

What is the role of the ribosome in protein synthesis?

Compare translation initiation in prokaryotes and eukaryotes.

6A: Lecture 6.4: Eukaryotic Transcription & Regulation. Dr Jan Frayne. DNA packaging. Transcription in eukaryotics: eukaryotic promoters, transcription factors, tissue specific expression and the regulation of transcription. Questions:

What DNA features and proteins are necessary for a mRNA transcript to be expressed in a tissue restricted manner?

6A: Lecture 6.5: Human Genome, Mutations & Genetic Disease. Dr Jan Frayne. Introns, exons, repetitive DNA, SNPs etc. Mutations in coding and non-coding DNA and genetic disease. Epigenetics. Questions:

Only small amounts of the human genome consist of genes. What other types of DNA are present in our genome?

What effect(s) could a single base pair change in the coding region of a human gene have on the resultant protein product?

6A: Lecture 6.6: Recombinant DNA Technology 1. Dr Jan Frayne. Restriction enzymes, Southern blots and their use for the detection of genetic disease. Questions:

What are restriction enzymes and how are they used in the construction of recombinant DNA molecules in vitro?

How can a Southern blot be used to detect genetic disease?

6A: Lecture 6.7: Recombinant DNA Technology 2. Dr Jan Frayne. DNA cloning: plasmids, gDNA, cDNA, Polymerase chain reaction and its applications. Gene therapy. Questions:

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Why are plasmids used as vectors in molecular biology?

Given the DNA sequence for glucose-6-phosphate dehydrogenase, how would you use P.C.R. to detect whether an individual carries a mutation in this gene?

6A: Lecture 6.8: Genomes, Transcriptomes & Proteomes. Dr Jan Frayne. Application of recombinant DNA technology to molecular medicine. Information derived from the technologies of genomics, transcriptomics and proteomics. Questions:

What different information can be obtained from the technologies of genomics, transcriptomics and proteomics?

How can recombinant DNA techniques be utilised for molecular medicine?

6B: Lecture 6.9: Introduction: Mitosis & Meiosis: Karyotypes. Dr Kathleen Gillespie. Significance of genetic diseases in medicine. Organisation of genetic information into chromosomes. Anatomy of a chromosome. Cell division cycle. Overview of mitosis & meiosis. Method of preparation of a karyotype and banding. Anatomy of chromosomes; methods of chromosome identification. Questions:

What are the differences between meiosis I and meiosis II?

How are different chromosomes distinguished, and does this reflect their underlying DNA organisation or function?

6B: Lecture 6.10: Numerical & structural abnormalities of chromosomes. Dr Kathleen Gillespie. Common autosomal and sex chromosome aneuploidies. Non-disjunction in meiosis I and II. Structural anomalies involving one or more chromosomes, deletion, duplications, reciprocal translocations (balanced and unbalanced), Robertsonian translocations. Questions

Most patients with Down’s syndrome have 47 chromosomes, but some have only 46. Why?

What are the possible gametes resulting from a 13/15 Robertsonian translocation, and what would be the clinical effects after successful fertilization in each case?

6B: Lecture 6.11: Introduction to single gene disorders (dominant & recessive). Dr Kathleen Gillespie. Pedigree drawing. Autosomal dominant disorders (e.g. Huntington’s chorea). Inherited vs. new mutations. Variability in expression/penetrance. Differential mutation rates. Autosomal recessive disorders (e.g. cystic fibrosis): pedigree risks, carrier risks in families, ethnic variations, consanguinity. Questions:

What are typical pedigrees for autosomal dominant, autosomal recessive and X-linked inheritance?

Would you expect a dominantly inherited condition to always have a previous family history? Why?

6B: Lecture 6.12: Sex chromosomes & X-linked inheritance. Dr Kathleen Gillespie. Chromosomal sex determination. Sex chromosome anomalies (X0, XXY, XYY), X-chromosome inactivation. X-linked inheritance (e.g. DMD): pedigree pattern, genetic risks, manifesting carriers. Fragile-X syndrome. Questions:

What serological evidence do we have in support of X-chromosome inactivation?

List some of the characteristic clinical and molecular features of Fragile-X syndrome.

6B: Lecture 6.13: Gene mapping, the human genome project. Linkage disequilibrium and the Hap-Map project. Multifactorial/polygenic inheritance and susceptibility to common diseases. Dr Kathleen Gillespie. Definitions. How interacting genes give continuously variable traits (including liability to disease). The Threshold model. The human genome project: DNA sequencing. Linkage disequilibrium and the “Hap Map” Project. Genetic effects across a range of common diseases.

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Questions:

What is the evidence that multiple genes and environmental factors contribute to susceptibility to complex disease

What is linkage disequilibrium and how has it contributes to recent identification of susceptibility genes for common disease

6B: Lecture 6.14: Population genetics. Dr Kathleen Gillespie. Hardy Weinberg equilibrium and its applications. Factors disturbing H-W equilibrium: non-random mating, altered mutation rate, positive/negative selection, founder effect and genetic drift in small populations, gene migration. Questions

Cystic fibrosis occurs in approximately 1/2000 individuals. Use the H-W law to calculate the carrier frequency.

What is the impact of selection on gene frequency?

PRACTICAL (see practical and tutorial book) Practical 4: “The diagnosis of Sickle Cell Anaemia” Wed 29th January, 10:00: B1 – B8 Thurs 30th January, 10:00: A1 – A8 Fri 31st January, 14:00: A9 – A12, B9 – B12

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ELEMENT 7

NUTRITION & METABOLIC DISEASES Element Organisers: Dr Kelly Moule & Dr Elinor Griffiths, School of Biochemistry, Medical

Sciences Building. Element Teachers: Dr Kelly Moule & Dr Elinor Griffiths, School of Biochemistry, Medical

Sciences Building.

OVERVIEW The Element contains 10 lectures. Please check your MCBoM timetable on Blackboard for venues of lectures. The first six lectures are given by Dr Kelly Moule, and the remaining four by Dr Elinor Griffiths. TIMETABLE

DATE TIME SESSION

Tues 28th January 12:00 7.1: Introduction. Selection of an adequate diet

Wed 29th January 09:00 7.2: Energy balance and bodyweight control

Fri 31st January 10:00 7.3: Dietary carbohydrate I

Fri 31st January 11:00 7.4: Dietary carbohydrate II

Mon 3rd February 11:00 7.5: Dietary Lipids I

Mon 3rd February 14:00 7.7: Dietary Protein I

Mon 3rd February 15:00 7.8: Dietary Protein II

Mon 3rd February 16:00 7.6: Dietary Lipids II

Tues 4th February 14:00 7.9: Minerals, trace elements and vitamins I

Tues 4th February 15:00 7.10: Minerals, trace elements and vitamins II

PREREQUISITES You should be familiar with the contents of Elements 2, 4 and 6. AIMS The Element aims to ensure that you are aware of the basic principles of nutrition and in particular:

that the diet provides the chemicals required for the continuous production of energy and the synthesis of tissue components on which the maintenance of body structure and function depend

the factors which determine the chemical composition of a balanced diet, and the importance of energy balance in maintaining body weight

the importance of diet in health promotion and disease prevention, in preventing complications associated with some medical treatments, and in treating some cases of endocrine abnormality and congenital abnormalities of metabolism.

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OBJECTIVES By the end of the Element, students should:

be able to estimate total energy expenditure and relate this to the energy value of food and the regulation of body weight

understand the role of the fat cell and the relationship between diet, exercise and obesity

know what dietary carbohydrate requirements are, including fibre. Understand the influence of some inborn errors of metabolism in carbohydrate metabolism

understand the metabolism of alcohol

understand the importance of dietary lipid, including essential fatty acids

know how the digestion and absorption of ingested lipid occurs and how the transfer of fatty acids, triacylglycerols and cholesterol between tissues occur

understand the importance of cholesterol in the diet, and the pharmacological regulation of cholesterol metabolism

understand the concepts of nitrogen balance and protein turnover

be aware of daily nitrogen requirement

be aware of the idea of protein quality and its assessment

know the consequences of protein malnutrition

have a broad overview of amino acid metabolism, the importance of urea synthesis and the function of vitamin B6

know some of the inborn errors of nitrogen metabolism, including phenylketonuria

be aware of the functions of a range of vitamins and the effects of vitamin deficiencies

know how trace elements and vitamin E are involved in the detoxification of reactive oxygen species.

understand the regulation of uptake and storage of dietary iron and calcium.

LECTURES Lectures 1 & 2: Dr Kelly Moule: Introduction. Selection of an adequate diet. Energy balance and body-weight control. Dietary requirements: estimating nutrient intake; recommended daily intakes . Food labelling. Energy balance: estimating energy expenditure and energy values of foods. Measures of obesity. Adipose tissue. Overview of the regulation of food intake. Weight reducing diets and treatments. Questions:

What is known by the basal metabolic rate, resting energy expenditure and respiratory quotient?

Estimate the energy content of today's breakfast, stating clearly your assumptions. What proportion of your estimated daily energy expenditure does this represent?

What is the recommended composition of a healthy diet for an adult? Lectures 3 & 4: Dr Kelly Moule: Dietary carbohydrate. Food sources: carbohydrates naturally present and added sucrose and sweeteners. Requirement for carbohydrate: trends in carbohydrate consumption; guidelines. Digestion and absorption. Refined cereals and fibre. Glycaemic Index. Links between dietary fibre and diseases. Artificial sweeteners. Inborn errors in carbohydrate metabolism: lactose intolerance; fructose and galactose metabolism; glycogen storage diseases; glucose 6-phosphate dehydrogenase deficiency. Alcohol and its metabolism. Questions:

What foods would you chose to increase your intake of (i) water soluble fibre and (ii) insoluble fibre?

What symptoms are characteristic of lactose intolerance, what causes the disorder and what specific foods should be avoided?

What is the importance of glucose 6-phosphate dehydrogenase deficiency?

How is ethanol metabolised and how quickly?

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Lectures 5 & 6: Dr Kelly Moule: Dietary Lipids: Food sources of lipid, both animal and plant based. Dietary requirements; trends in availability and use of dietary fat. Relationships between saturated fat intake and health. Essential fatty acids. Lipid emulsification, digestion, absorption and transport within the body. Classification and importance of plasma lipoproteins. Exogenous and endogenous pathways of lipid transfer. Cholesterol metabolism. Questions:

Give examples of foods containing saturated, mono-unsaturated and poly-unsaturated fats. Which fatty acids are essential in the diet and why?

Distinguish between chylomicrons, VLDL, IDL, LDL, HDL.

What is the role of lipoprotein lipase?

List the roles of cholesterol in the body. What foods can increase the amount of cholesterol within blood LDL?

Lectures 7 & 8: Dr E Griffiths: Dietary Protein. Amino acids from dietary protein are a major source of nitrogen atoms for the synthesis of proteins, DNA and many other important biological molecules. The concept of protein turnover. Nitrogen balance and its assessment. Dietary nitrogen requirement. Essential and non-essential amino acids. Types of dietary protein and its assessment, factors influencing optimal protein intake. Protein deficiency - malnutrition, kwashiorkor. Brief account of intestinal digestion and absorption of protein. General principles in amino acid metabolism - lack of storage forms of amino acids; ammonia toxicity. Inter-organ transfer of amino acids. General outline of transamination, the urea cycle, glutamine synthesis and pathways of metabolism of the carbon skeletons of amino acids. importance of vitamin B6 mechanism of action, effect of B6 deficiency. Inborn errors of amino acid metabolism with particular emphasis on phenylketonuria - detection, management and biochemical nature of the inherited defect. Questions:

What is meant by: i) protein turnover ii) nitrogen balance iii) an essential amino acid iv) protein quality and its evaluation

What is the biochemical function of vitamin B6?

What is the biochemical basis of phenylketonuria? How is the condition treated? Lectures 9 & 10: Dr E Griffiths: Vitamins, minerals and trace elements: Vitamins: definition; sources and recommended intakes. Vitamins as enzyme cofactors. Specific consideration of functions of vitamin A in vision, vitamin C in collagen synthesis, vitamin K in blood clotting, vitamin D in Ca2+ absorption and folic acid in DNA synthesis. Warfarin and methotrexate as clinically useful vitamin antagonists. Effect of deficiencies and excessive intake of various vitamins. Minerals: requirements, sources, effect of deficiencies. Trace elements: - outline of requirements and dietary sources. Detailed consideration of iron uptake, transport storage and utilisation. Oxygen toxicity. Role of trace elements and vitamins A,C and E in the detoxification of reactive oxygen species. Questions:

What are the most common vitamin deficiencies?

Certain drugs act by antagonising the action of vitamins. How do (a) warfarin (dicoumarol) and (b) methotrexate work?

Which trace elements are thought to be important in the detoxification of reactive oxygen species and why?

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ELEMENT 8

INFECTION & IMMUNITY

OVERVIEW

Element Organiser: Dr David Morgan, School of Cellular & Molecular Medicine (CMM), Room E48, Medical Sciences Building (tel: 0117 331 2021, email: [email protected])

The Element comprises 38 lectures, 2 practicals and 3 tutorials. Please check your MCBoM timetable on Blackboard for venues of lectures. Histology Practicals are in TL 2.2. The Element will review aspects of inflammation, immunology and microbial infection.

TIMETABLE

Section 8A: Inflammation & Repair

DATE TIME SESSION

Mon 27th January 09:00 8.1: Cell & Tissue Damage I

Mon 27th January 10:00 8.2: Cell & Tissue Damage II

Tues 28th January 11:00 8.3: Acute Inflammation I

Tues 28th January 14:00 8.4: Acute Inflammation II

Weds 29th January 10:00 CMM Tutorial 1: Pathology & Inflammation (A1 – A8)

Weds 29th January 11:00 CMM Tutorial 1: Pathology & Inflammation (AB9 – 12)

Thurs 30th January 09:00 CMM Tutorial 1: Pathology & Inflammation (B1 – B8)

Mon 3rd February 09:00 8.5: Chronic Inflammation I

Mon 3rd February 12:00 8.6: Chronic Inflammation II

Tues 4th February 10:00 8.7: Radiation

Tues 4th February 11:00 8.8: Healing & Repair

Thurs 6th February 09:00 8.9: Amyloid

Section 8B: Immunology

DATE TIME SESSION

Thurs 6th February 10:00 8.10: Innate Immunity I

Thurs 6th February 11:00 8.11: Innate Immunity II

Fri 7th February 10:00 8.13: Recognition of Innumerable Antigens

Fri 7th February 12:00 8.14: Transplantation & HLA

Mon 10th February 12:00 8.15: T-cell Subsets I, II

Mon 10th February 14:00 8.16: T-cell Subsets III

Mon 10th February 15:00 CMM Tutorial 2: Immunology (Group A)

Mon 10th February 16:00 8.17: Effector Mechanisms: Helpful & Harmful I

Tues 11th February 09:00 8.18: Effector Mechanisms: Helpful & Harmful II

Tues 11th February 12:00 8.19: Immunodeficiencies

Wed 12th February 09:00 8.20: Immune Tolerance & Autoimmunity

Wed 12th February 10:00 CMM Tutorial 2: Immunology (Group B)

Thurs 13th February 10:00 CMM Tutorial 2: Immunology (Group C)

Thurs 13th February 11:00 CMM Tutorial 2: Immunology (Group D)

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Section 8C: Infection

DATE TIME SESSION

Fri 14th February 12:00 8.22: Virus Structure & Classification

Mon 17th February 09:00 8.23: Viral Replication

Mon 17th February 11:00 8.24: Introduction to Medical Bacteriology

Mon 17th February 16:00 8.25: Bacterial Structure & Virulence Factors

Tues 18th February 09:00 8.26: Viral Pathogenesis

Tues 18th February 10:00 8.27: Parasites

Tues 18th February 11:00 8.28: Eukaryotics (fungi)

Tues 18th February 12:00 8.29: Normal Microbiota

Wed 19th February 09:00 8.30: Host-pathogen Interactions

Section 8D: Control of Infectious Disease

DATE TIME SESSION

Fri 21st February 09:00 8.31: Dysregulation of the Host Response to Infection

Fri 21st February 10:00 8.32: Epidemiology of Infectious Diseases

Fri 21st February 12:00 8.33: Hospital Acquired Infection

Mon 24th February 09:00 8.34: Emerging Infectious Diseases

Tues 25th February 09:00 8.35: Antimicrobials: Introduction & Modes of Action

Tues 25th February 10:00 8.36: Important Antibiotics & Antimicrobial resistance

Tues 25th February 12:00 CMM Tutorial 3: Microbiology (A9 – A12, B9 – B12)

Wed 26th February 09:00 CMM Tutorial 3: Microbiology (A1 – A8)

Wed 26th February 10:00 CMM Tutorial 3: Microbiology (B1 – B8)

Fri 28th February 09:00 8.37: Immunisation

Fri 28th February 12:00 8.38: Control of Infection

AIMS The aim of this Element is to introduce the student to the concepts which underlie cellular pathology and the causation of diseases including infection by microbes and the host response to such insult, and to introduce terms and concepts which will be essential language throughout the rest of their studies. In order to achieve this, the Element will provide basic information concerning:

how tissues respond to damage and the underlying mechanisms involved in healing and repair

the biology of the groups of organisms that are capable of causing disease in man (bacteria, viruses, protozoa, helminths and fungi) and how they have evolved to use the human body as a site for growth; how organisms are spread between individuals and how knowledge of the mechanisms is used to help prevent and treat infectious disease in the host population;

how man adapts to prevent infection following damage;

the non-specific events surrounding the inflammatory response, linked to a study of the organisation and function of the immune system;

the ways in which the immune system is involved in clearing infectious material, coupled with information concerning how the immune response may actually be damaging to the host (hypersensitivity and autoimmunity).

OBJECTIVES

When you have finished the Element you should:

understand the pathological processes of inflammation, cell and tissue damage, and repair at the tissue, cellular and molecular level.

understand the role of inflammation in bringing in and activating components of the immune system.

know the distinct components of the humoral and cell mediated immune response and the importance of the interactions between them.

understand how the immune response may be involved in causing pathology as a result of its inappropriate activation to foreign components (allergy) and self proteins (autoimmunity).

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know the structure and physiology of microorganisms, comparing them with each other and with host cells.

state the organisms involved in common infective processes.

understand the concepts of commensalism and pathogenicity, the microbial properties relating to pathogenesis and the links between commensalism and opportunist infections.

understand how microorganisms are transmitted and the epidemiology of common infections in the hospital and community.

understand the principles underlying methods of sterilisation and disinfection and aseptic procedures.

list the mechanisms of action of the major antimicrobial agents and their spectra of activity.

understand how resistance to antimicrobial agents is acquired and the mechanisms that are involved.

apply your knowledge of antimicrobial agents to the choice of treatment and the devising of policies.

ELEMENT 8A: INFLAMMATION AND REPAIR

Lecture 8.1: Cell and Tissue Damage I. Dr E Foulstone. Cells can be damaged in a variety of ways. Following cellular injury, cells die either by apoptosis or necrosis. Questions:

What are the major causes of tissue injury?

What are the characteristic features of a) necrosis and b) apoptosis?

Lecture 8.2: Cell and Tissue Damage II. Dr E Foulstone. Distinct types of necrosis are described. They occur in different pathological situations. Questions:

What are the key features of i) gangrene, ii) caseation, iii) coagulative necrosis?

What adaptive changes occur in tissues subjected to sublethal injury?

Lecture 8.3: Acute Inflammation I. Dr M Sohail. Acute inflammation is the early local response to tissue injury which may be brought about by a variety of causes. The physical characteristics of acute inflammation are well recognised. Questions:

What is inflammation? What are the salient macroscopic and microscopic features of acute inflammation?

What are the known causes of acute inflammation?

Lecture 8.4: Acute Inflammation II. Dr M Sohail. A lot is known about the cellular and chemical basis of acute inflammation. Acute inflammation may have both beneficial and harmful effects. Questions:

How is acute inflammation beneficial to the host?

What are the major chemical mediators of acute inflammation?

What are the vascular changes of acute inflammation?

Lecture 8.5: Chronic Inflammation I. Dr M Sohail. Chronic inflammation lasts longer than acute inflammation and is characterised by progressive tissue damage occurring together with attempts at eradicating the stimulus. The physical characteristics and cellular components of chronic inflammation are well described. Question:

What are the differences in the cellular mechanisms underlying acute and chronic inflammation?

Lecture 8.6: Chronic Inflammation II. Dr M Sohail. Chronic inflammation results from a variety of stimuli. Specific forms of chronic inflammation e.g. granulomatous inflammation occur in a variety of human diseases.

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Questions:

What are the causes of chronic inflammation?

What are the features of chronic inflammation as it occurs in tuberculosis?

Lecture 8.7: Biological Effects of Radiation. Dr M Sohail. This lecture will review the physics of electromagnetic and particulate radiation and describe different forms of radiation-damaged tissue. Focus on mechanisms of protein and DNA damage, acute and chronic radiation effects, the effect of radiation dose, mechanisms of radiation treatment in oncology and the different sensitivities of tissues to radiation. Questions:

What tissues of the body are particularly sensitive to radiation? How does radiation damage tissue?

Why is radiotherapy effective in treatment of cancer?

Lecture 8.8: Healing & Repair. Dr M Sohail. Tissue damage is followed by either restitution or organisation and repair. The physical characteristics of the process of healing are associated with a number of cellular events. Questions:

What is the sequence of events that lead to scar formation in a skin wound?

What local and systemic factors are important in the process of healing?

Lecture 8.9: Amyloid. Amyloid is the name given to a group of proteins that are deposited at extracellular sites. The lecture will detail the classification and general clinical effects of amyloidosis. Questions:

Define and classify amyloidosis.

Give two examples of the clinical manifestations of local amyloidosis.

ELEMENT 8B: IMMUNOLOGY

The Basis of the Immune System. Definitions of antigens / immunogens and antibodies. Classification of the immune response into humoral and cell mediated, and introduction to the basic concepts underlying kinetics of immune responses (specificity and memory). Questions:

What are the advantages to man of having a specific immune response?

What is meant by the terms: antigen, immunogen, antibody?

Lecture 8.10: Innate Immunity I. Dr DJ Morgan. What is there to stop microorganisms from entering the human body? This lecture will detail the physical and chemical means by which the body prevents invasion by microorganisms. The body surface, the initial environment encountered when microbes enter the tissues. Question:

What are the major barriers which microorganisms must be able to overcome if they want to colonise the tissues?

Lecture 8.11: Innate Immunity II. Dr DJ Morgan. Classification of the determinants of innate immunity and the relationship between inflammation and immunity; and the distinction between acquired (specific) and innate (non-specific) immunity. Questions:

Distinguish between the acquired immune response and innate immunity.

What is the relationship between inflammation, innate immunity and the acquired immune response?

List the means by which phagocytes kill ingested particles.

Lecture 8.13: Recognition of Innumerable Antigens. Professor N Williams. How can the immune system recognise all the possible antigens? Discussion of the structures used by the immune system to recognise antigen. Immunoglobulin as an antigen receptor for the humoral immune response and the T-cell

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receptor as the antigen receptor for the cell mediated immune system. How do we produce structures which allow recognition of all possible antigens? Questions:

Answer the question posed by the lecture title.

What is the structure and genetics of the immunoglobulin molecule?

List the different subclasses of immunoglobulins.

Lecture 8.14: Transplantation & HLA. Professor N Williams. Transplantation immunity and definition of histocompatibility antigens. Description of Class I & II major histocompatibility complex (MHC) molecules. Classification of human leukocyte locus A (HLA) antigens. Questions:

By what mechanisms are tissues grafted from one individual to another (allografts) usually rejected?

Understand histocompatibility antigens.

Annotate a diagram of the basic structure of Class I and Class II molecules.

How matching HLA antigens of donor and recipient and treatment with selective immunosuppressive agents prolongs graft survival.

What is graft versus host disease?

Lectures 8.15: T-cell Subsets I. Professor N Williams. Association between particular HLA antigens and disease. Classification of T-cell subsets. Description of cytotoxic T-cells and MHC haplotype restriction. Questions:

What is the association between particular HLA antigens and disease? Give examples.

Classify T-cell subsets.

How do CTL kill virally infected cells?

How do T-cells recognise antigenic peptides bound by histocompatibility antigens?

What is the function of histocompatibility antigens?

What is MHC haplotype restriction?

T-cell Subsets II. Professor N Williams. Cytotoxic T-cells, CD8 and Class I restriction. Helper T-cells, CD4 and Class II restriction. Function of Th-1 cells. Definition of cytokines. Questions:

What is the function of CD8, and how Tc are MHC Class I restricted?

What is the function of CD4, and how Th are MHC Class II restricted?

What is meant by the term cytokine and give examples of how they act?

Lecture 8.16: T-cell Subsets III. Professor N Williams. Evidence for T-B collaboration in initiation of antibody response. Requirement of antigen presenting cells (APC) for stimulation of T-cells. Distinction between exogenous and endogenous pathways of presentation. Description of cognate, mutual interaction between antigen specific B and T-cells, release of Th2 cytokines and delivery of second signal to B-cells. Concept of B-cells as antigen specific APC. Questions:

What is the evidence for T-cell involvement in initiation of antibody responses?

What is the difference between the exogenous and endogenous pathways of presentation?

List the cytokines that promote B-cell proliferation and maturation to plasma cells.

How do antigen specific B-cells internalise antigen, cleave it and present antigenic peptides on its surface that antigen specific Th2 cells recognize?

Lecture 8.17: Effector Mechanisms: Helpful & Harmful I. Dr DJ Morgan. Classification of hypersensitivity reactions. Description of type I reactions, anaphylaxis, allergy and IgE. IgE initiated inflammation in parasite immunity. Questions:

Define and classify hypersensitivity reactions.

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What is the difference between localised and systemic anaphylaxis and give examples of each?

How does cross linking of IgE on mast cells stimulate degranulation?

What is the role of IgE antibodies in parasite immunity?

Lecture 8.18: Effector Mechanisms: Helpful & Harmful II. Dr DJ Morgan. Illustrations and mechanisms of type II (e.g. transfusion reactions, Rh disease and its prevention), type III (e.g. systemic lupus) and type IV (e.g. tuberculin reaction) hypersensitivity reactions. Description of complement cascade. Questions:

List with examples the mechanisms of types II, III and IV hypersensitivity reactions.

What is complement?

What are the effects of complement activation?

Lecture 8.19: Immunodeficiencies. Dr DJ Morgan. Definition of primary and secondary immunodeficiencies, AIDS. Questions:

How do genetic defects in lymphocyte development give rise to primary immunodeficiencies?

Give an example of a selective immunodeficiency.

What is the evidence that HIV causes AIDS?

How is CD4 involved in AIDS?

Lecture 8.20: Immune Tolerance and Autoimmunity. Dr DJ Morgan Immunological Tolerance. Definition of immunological tolerance. Mechanisms by which autoreactive cells are deleted or prevented from responding to autoantigens. Stimulation of autoreactive cells. Questions:

What is the definition of immunological tolerance?

What is meant by clonal deletion, and describe evidence for it?

How may autoreactive B-cells and T-cells escape clonal deletion?

What is the evidence that autoimmune reactions are responsible for the pathogenesis of autoimmune diseases?

Give examples of autoimmune diseases and their pathology.

ELEMENT 8C: INFECTION

Lecture 8.22: Virus Structure & Classification. Professor S Siddell. Classification, structure and composition of viruses. Overview of human viruses. Virus diagnostics Questions:

What are the various different structures of viruses?

Compare the different approaches to virus diagnostics.

Lecture 8.23: Viral Replication. Professor S Siddell. How viruses replicate. Examples of retrovirus replication. Targets for intervention. Questions:

What are the essential phases of retrovirus replication?

How do antiretroviral drugs work?

Lecture 8.24: Introduction to Medical Bacteriology. Dr Darryl Hill. An overview of the relationship between man and bacteria in health and disease. An introduction to bacterial structure highlighting the differences between eucaryotic cells and the procaryotic bacteria. Questions:

Differentiate between the terms ‘colonisation’ and ‘infection’.

List the key structural and physiological differences between microorganisms, and host cells.

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Lecture 8.25: Bacterial Structure & Virulence Factors. Dr Darryl Hill. An introduction to the physiology and structure of bacteria and how this aids their ability to cause disease. Description of bacterial structure highlighting the differences between Gram-positive and Gram-negative organisms. A brief overview of how bacteria can sense and respond to changes outside their cell Questions:

What is the structure of a typical bacterial cell and how the various structural characteristics aid their ability to cause disease?

What are the differences between Gram-positive and Gram-negative bacteria?

Lecture 8.26: Viral Pathogenesis. Professor S Siddell. Mechanisms underlying acute, latent and persistent viral infections. Localised and systemic infection. Respiratory, enteric & neurological infections and haemorrhagic fevers.

What are the different patterns of virus disease?

List the major features regarding the pathogenesis of a typical systemic virus infection.

Lecture 8.27: Parasites. Prof W Gibson. Protozoa, filaria, flukes and tapeworms; their global importance, life cycles and ways of transmission. Differences between the micro and macroparasites and the immune response to them. Major disease caused by intracellular, tissue and gut dwelling parasites. Efforts to prevent infections. Questions:

How and why are the immune responses different to micro and macroparasites?

What are the major complications of cerebral malaria?

In what circumstances can Toxoplasma infection become a threat?

Lecture 8.28: Eukaryotics (fungi). Dr E Johnson. An introduction to the biology of fungi and fungal infections. The lecture will include an overview of both superficial and systemic infections caused by yeasts and moulds with discussion of modes of acquisition and pre-disposing factors. Questions:

What are the differences between superficial infections caused by dermatophytes and yeasts?

What combinations of host and organism factors allow fungi to act as opportunistic pathogens?

Lecture 8.29: Normal Microbiota. Dr J Leeming. Many organisms are able to colonise the human body and are more usually helpful to the host rather than disease causing. However under certain circumstances such commensals can cause disease. The lecture explores both the normal situation and the factors associated with its alteration. Questions

Define the concept of an opportunistic infection with examples of infecting agents and the preconditions required for them to cause disease.

Why can administration of antibiotics make patients more susceptible to some infections? Name two infections for which recent consumption of antibiotics is a risk factor.

Lectures 8.30: Host-Pathogen interactions. Dr Darryl Hill. Overview of the dynamic interaction between pathogens and the human host during health and disease. Balance between host defence mechanisms and pathogen virulence determinants, with specific examples. Questions:

What are the anti-pathogen defence mechanisms of the body?

How do pathogens attempt to overcome human defence systems and thereby cause clinical disease?

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ELEMENT 8D: CONTROL OF INFECTIOUS DISEASE

Lecture 8.31: Dysregulation of the Host Response to Infection. Dr Darryl Hill. Inappropriate host responses to infection can exacerbate disease. Mechanisms by which pathogens can subvert the host response, using specific examples. Questions:

How do pathogens subvert the host response to infection?

Give examples of how an inappropriate host response can lead to disease.

Lecture 8.32: Epidemiology of Infectious Diseases. Dr Mahableshwar Albur. The basic terms used in epidemiology. Understanding the infectious process and how infection spreads. How outbreaks of infectious diseases occur. Collection of epidemiological data. Questions:

What is meant by the terms: prevalence, incidence, endemic, epidemic, and pandemic?

Why do infectious diseases spread though a community?

Lecture 8.33: Hospital Acquired Infection. Dr A Cochrane. Hospital acquired infections encompass all types of infection acquired by patients while being cared for in hospital. Risk factors for acquisition of infection and pathogens commonly associated with hospital acquired infection. Questions:

Choose two types of patient that you would consider to be at high risk of acquiring an infection in hospital. Explain why they are at high risk and describe the common routes by which they may contract a hospital (nosocomial) infection

The use of invasive procedures and devices is becoming common routine in modern medical practice. Describe the types of infection associated with invasive devices and procedures, suggesting ways by which such infections can be minimised.

Lecture 8.34: Emerging Infectious Diseases. Dr Mahableshwar Albur. The importance of infectious diseases in terms of worldwide morbidity and mortality. The emergence of new infectious diseases and the re-emergence of old infectious diseases. Host and pathogenic factors that have led to this process. Questions:

What are the most important infectious diseases worldwide?

What factors have led to the emergence of new infectious diseases?

Lecture 8.35: Antimicrobials: Introduction & Modes of Action of Antibiotics. Professor A MacGowan. The discovery and development of antibiotics. An overview of the currently available agents in terms of their microbial and molecular targets. Anti-bacterial agents, anti-viral agents, anti-fungal agents. Questions:

Describe the specific requirements which must be met for an antimicrobial agent to be useful in medicine.

List the major molecular targets used by modern antibiotics (providing examples).

Define the terms bactericidal and bacteriostatic.

Why are there fewer available anti-viral drugs than those that kill bacteria?

Lecture 8.36: Important Antibiotics & Antimicrobial Resistance. Professor A MacGowan. A detailed account of antibiotics which act on the cell wall of bacteria with examples of the precise mechanisms of action and the range of organisms for which commonly used agents are useful. The considerations involved in the choice of an antimicrobial for treatment, including the problem of antibiotic resistance. Questions:

“The bacterial cell wall continues to provide an ideal target for antibiotic action”. Be able to understand this statement.

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How is bacterial cell wall formed, and what are the major points where disruption of the process by antibiotics occurs?

How does the doctor decide which antimicrobial is the correct choice for a patient?

Lecture 8.37: Immunisation. Professor N Williams. The aims and considerations underlying attempts to immunise members of the population against infectious disease. Difficulties of vaccine design and delivery. Commonly used vaccines. Questions:

List with examples the types of vaccine available for use in man

What agents may be used to enhance the effectiveness of antigenic challenge in stimulating protective immunity?

Lecture 8.38: Control of Infection. Dr A Cochrane. Describes the principles of how infections are spread in hospital and community. Measures and strategies available for preventing acquisition of and controlling spread of infection. Examples of outbreak management from recent experience. The role of the Infection Control Team in hospital and the Consultant in Communicable Disease Control in the community. Questions:

How are infections acquired and spread within the hospital environment? Give named examples of organisms spread by each method of transmission.

How can viral diarrhoea and vomiting be spread in hospital? How can the spread of infection by controlled?

PRACTICAL CLASSES

1) Histology Practical 4: Histology of blood cells. In TL 2.2 (Margaret Gatumu) Thurs 12th December, 10:00: A1 – A12 Thurs 12th December, 14:00: B1 – B12 2) Histology Practical 5: Lymphoid tissue histology. In TL 2.2 (Margaret Gatumu) Thurs 19th December, 10:00: A1 - A12 Thurs 19th December, 14:00: B1 - B12

TUTORIALS You will have an opportunity to raise questions about the topics covered in the associated lectures and to practice examination questions.

FURTHER READING You may find the following web sites useful for further information. John Hopkins AIDS http://www.hopkins-aids.edu Health Protection Agency http://www.hpa.org.uk WHO http://www.who.int Department of Health http://www.doh.gov.uk British Society for Immunology http://www.immunology.org/page.aspx?pid=1054

http://www.hopkins-aids.edu/

http://www.hpa.org.uk/

http://www.who.int/

http://www.doh.gov.uk/

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ELEMENT 9

THE MOLECULAR BASIS OF CANCER OVERVIEW

Element Organiser: Dr David Morgan, School of Cellular & Molecular Medicine (CMM), Room E48, Medical Sciences Building

(tel: 0117 331 2021, email: [email protected])

This Element contains 13 lectures and 1 tutorial. Please check your MCBoM timetable on Blackboard for venues of lectures.

TIMETABLE

DATE TIME SESSION

Mon 3rd March 09:00 9.1: Normal cell growth I

Mon 3rd March 10:00 9.2: Normal cell growth II

Tues 4th March 09:00 9.3: Oncogenes & tumour suppressor genes

Tues 4th March 10:00 9.4: Cancer of the colon

Wed 5th March 09:00 CMM Tutorial 4 (Cancer)(A1 – A8)

Thurs 6th March 09:00 9.6: Classification of tumours

Fri 7th March 09:00 C & MM Tutorial 4 (Cancer)(B1 – B8)

Fri 7th March 10:00 C & MM Tutorial 4 (Cancer)(A9 – A12, B9 – B12)

Fri 7th March 11:00 9.7: Multistage development of cancer

Fri 7th March 12:00 9.8: The Immune system fails to control cancer

Mon 10th March 10:00 9.9: Spread of cancer

Mon 10th March 11:00 9.10: Cancer causing agents

Tues 11th March 09:00 9.11: Hormones & cancer

Tues 11th March 10:00 9.12: Cancer prevention

Wed 12th March 09:00 9.13: Treatment of cancer

Thurs 13th March 09:00 9.14: Diagnosis of cancer: case presentations

PRE-REQUISITES

You should review the coverage in previous Elements of: the histology of different types of epithelia, glands and connective tissue; the ultrastructure and function of cell membranes and the way cell behaviour is influenced by: (i)

hormones, neurotransmitters & cytokines and (ii) adhesion molecules & the extracellular matrix, including receptors, signal transduction pathways, and transcriptional activation;

basic molecular biology including: genes, DNA & the genetic code; transcription; translation; the cellular basis of differentiation; & mutations amplifications and translocations;

the biology of cell division: meiosis & mitosis; the cell cycle; chromosomes and karyotypes; the control of gene replication;

basic immunology; the biology of RNA & DNA viruses.

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AIMS

The Element aims to provide students with an understanding of the basic biology of cancer, and how this basic biology determines our approach to patients.

OBJECTIVES By the end of this Element, the student should understand:

the concepts of cell proliferation and differentiation and how these relate to the cell cycle in different cell populations

how cell proliferation and differentiation is controlled and how these control mechanisms can fail that neoplasia is a multistep process characterised by sequential alterations in a number of oncogenes

and tumour suppressor genes the multistep of cancer as it applies to the colon that different groups of people are more susceptible to particular cancers and how this susceptibility

relates to genetic and environmental factors the role of environmental factors, including viruses, in carcinogenesis the nomenclature and broad classification of tumours, and the general characteristics of tumours in

terms of clinical behaviour, morphological changes, molecular biological and cytogenetic features the routes and mechanisms by which cancers spread the general effects of cancer the general ineffectiveness of the immune system in preventing the development of cancer the relationship between many tumours and certain hormones principles of prevention and treatment of cancer

LECTURE SYNOPSES Lecture 9.1: Normal cell 1. Prof A Williams. After foetal development some cell populations mature and some continue to proliferate. To perform their specific functions cells have to stop proliferating: specialisation of function requires differentiation. The lecture explains the concepts of cell proliferation and differentiation: Questions:

What is the cell cycle: what events take place in each of the different phases of the cell cycle?

What is differentiation? By what mechanisms do cells differentiate and what are the features of the differentiated state?

Lecture 9.2: Cell growth 2. Prof A Williams. Tissue homeostasis is maintained through a balance of proliferation, differentiation and apoptosis. Using the intestinal epithelium as a model, the lecture aims to describe how cell numbers within the tissue are maintained and how loss of this control can lead to cancer. Questions:

How are cell numbers maintained within the intestinal epithelium?

Describe the intracellular signaling cascade that results in apoptosis? What are the differences between apoptosis and necrosis?

Why is ‘evading apoptosis’ one of the hallmarks of cancer?

Lecture 9.3: Oncogenes & tumour suppressor genes. Professor C Paraskeva. Proto-oncogenes are normal genes that produce factors which result in cell proliferation. Tumour suppressor genes are normal genes that produce factors which normally inhibit cell proliferation. Cancers often involve abnormal activation of several of the former (so proto-oncogenes become oncogenes by mutation or overexpression) and/or abnormal inactivation of the latter. Questions:

What are oncogenes? How were they discovered? How do oncogenes (such as myc and ras) contribute towards the development of neoplasia?

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What are tumour suppressor genes? How do they contribute to the development of neoplasia? Illustrateyour answer with reference to p53 and Rb genes.

Lecture 9.4: Molecular pathology: cancer of the colon. Professor C Paraskeva. Cancer of the colon is very common. More is known about the roles of oncogenes and tumour suppressor genes in the development of this cancer than of any other. Question

What oncogenes and tumour-suppressor genes are involved in the development of colon cancer?

Epidemiology of cancer. Dr DJ Morgan. Most cancers have characteristic geographic distribution or have a higher incidence in some groups of people than in others. In many cases this has led to the identification of both causes and mechanisms, relating to various genetic and environmental factors. Question:

How has the study of epidemiology of cancers contributed to our understanding of their causes. Illustrate your answer by reference to cancer of the colon, cancer of the lung, hepotocellular carcinoma.

Lecture 9.6: Classification of tumours. Dr M Sohail. Tumours are classified according to (i) organ of origin (ii) tissue of origin (iii) histological type and (iv) whether their behaviour is benign or malignant. They can be characterised in terms of their clinical behaviour, morphological change, molecular biological and cytogenetic features. Questions:

How do benign and malignant tumours differ from each other?

Describe the origin, characteristics and common sites of origin of the following tumours: a) adenocarcinoma b) osteosarcoma c) myeloid leukaemia d) teratoma e) choriocarcinoma

Lecture 9.7: Multistage development of cancer. Professor C Paraskeva. The development of cancer (neoplasia) is a multistep process characterised by sequential acquisition of defects in a number of oncogenes and tumour suppressor genes. The different defects may have different causes. Question:

Cancer occurs in a multistep process. What is the evidence in terms of (a) clinical behaviour of tumours (b) histological features, (c) experimental cell biology (d) molecular biology.

Lecture 9.8: The Immune system fails to control cancer. Dr D Morgan. The immune system is usually ineffective in preventing the development of cancer. Some tumour products such as hormones and peptides serve as useful immunological markers for the presence of the tumour. Question:

What evidence is there for an immunological reaction against cancers and why is it so often ineffective?

Lecture 9.9: Spread of cancer. Dr M Sohail. Cancers spread throughout the body by various routes. Much is known about the mechanisms of tumour spread and the general effects of cancer including those related to the production of hormones by some tumours. Staging and grading is a way of describing the progression of tumours. Questions:

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By what routes do malignant tumours spread in the body? What is known about the mechanisms which influence these?

What factors determine prognosis of malignant tumours?

Lecture 9.10: Cancer causing agents. Dr M Sohail. Many environmental influences are known to be associated with the development of cancer. These include viruses, chemicals, diet and ionising radiation. Questions:

Write an essay on viral causes of human cancers.

Write an essay on occupational causes of cancer.

Lecture 9.11: Hormones & cancer. Dr M Sohail. Hormones may act as carcinogens. Some tumours produce hormones. Hormone therapy is effective with some cancers. Questions:

By what mechanisms do hormones enhance the development of neoplasia? Give 3 examples.

What hormonal effects may be associated with lung cancer?

Lecture 9.12: Cancer prevention. Professor C Paraskeva. It is possible to reduce the risk of some cancers and hence preventing cancer occurring. Screening programmes are devised to detect cancers while they are still curable. But there are some disadvantages in all screening programmes. Question:

How do we currently screen for cervical cancer?

Lecture 9.13: Treatment of cancer. Dr A Bahl. The treatment of cancer must be geared to the type, site and degree of spread of the tumour. Local cancers are usually treated surgically or with radiotherapy. Disseminated cancers will require systemic treatment, such as chemotherapy or hormone manipulation. Questions:

What are the mechanisms of action of cytotoxic chemotherapy and how does it result in tumour cell death, whilst it is tolerated by the patient?

What are the common acute side effects of chemotherapy and radiotherapy and why do they occur?

Lecture 9.14: Diagnosis of cancer: case presentations. Dr M Sohail. This is a clinical case presentation used to illustrate the cause, clinical effects and treatment of a common human cancer.

All information is correct at the time of print and is subject to change. You will be notified if and when any changes should occur.

year 1 mcbom unit handbook 2013/14 - university of bristol

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