Professor CW Taylor
Telephone: +44 1223 334058
Part II Pharmacology
There are two ways of studying pharmacology in Part II of the Tripos. Both share the same core teaching, but they differ in whether they include a practical research project (Part II Pharmacology) or a library dissertation and an additional single-paper Minor Subject (BBS). There is no practical work in the pharmacology component of the BBS course. Teaching takes place only during the Michaelmas and Lent Terms. The Easter Term is reserved for revision and exams.
Both courses can be equally demanding, but if you are considering postgraduate laboratory-based research (PhD or MB/PhD), you are strongly advised to take Pharmacology Part II. Most universities will expect applicants for such research degrees to have had the sort of laboratory experience that the Pharmacology Part II course provides.
Biological and Biomedical Sciences
|Laboratory-based research project|
|Library-based dissertation on a topic chosen from titles in Pharmacology or Minor Subject|
|Additional Minor Subject (chosen form a wide range).|
Most teaching is delivered by staff from the Department of Pharmacology. There are presently 18 University Teaching Officers and a number of senior researchers within the department. All are actively engaged in research and committed to teaching. Visitors from other departments and pharmaceutical companies complement the expertise of staff by providing some lectures and by supervising research projects. Weekly Tea Talks, which all students are expected to attend, provide a roughly equally mix of talks from the home team and from visitors. All lecturers are available to provide supervisions.
- The course aims to provide a balanced, critical and wide-ranging treatment of pharmacology as it relates to understanding mechanisms of drug action. It is not a course on therapeutics, although its focus on underlying mechanisms provides insight into both drug development and the use of drugs to treat disease. There is some emphasis on areas that reflect the research interests of teaching staff, although those interests range widely form molecular to behavioural pharmacology. By teaching to the bounds of current knowledge, the course aims to impart the excitement of current research in pharmacology and highlight some of the current controversies.
- The course educates students in a range of learning skills to equip them for careers in medicine, veterinary medicine and science, and for careers unrelated to pharmacology.
- For Part II Pharmacology students, the course educates students in practical skills to equip them for careers in medicine, veterinary medicine and science.
- To offer a course of lectures, tech talks, discussion groups, a statistics workshop, supervisions and tea talks in pharmacology. Lectures lie at the core of the course and define the syllabus. Tech talks, usually provided by senior research fellows, provide advanced reviews of techniques currently used in pharmacology. Discussion groups provide opportunities to present and critically evaluate the scientific literature, to review the presentations of your peers, and to present progress reports on projects or dissertations. Supervisions are available on all lecture courses. They allow issues arising from lectures or further reading to be pursued, and they provide opportunities for students to submit written work for comment. Tea talks are formal research presentations from internal and visiting speakers, which all students are expected to attend.
|To offer a laboratory-based supervised research project.||To offer a supervised library-based dissertation topic|
|Assessment is by written examinations. Past examination papers are available on-line. Candidates may also be required to attend an oral examination. In addition, the following means of assessment are specific to either of the two courses:|
|The research project is assessed by a report from the supervisor, submission of a written report, and assessment of a formal research seminar.||The research dissertation is assessed after submission of a written report and in an oral examination.|
At the end of the course students should be able to:
- Think critically and with an appropriate level of knowledge across a range of pharmacological topics.
- Effectively retrieve, evaluate and assimilate information from the scientific literature.
- Assess the feasibility of published methods to solve pharmacological problems.
- Communicate effectively with a scientific audience in oral and written presentations.
- Analyse and assess research methods and results during a supervised research project (Part II Pharmacology only).
Organization of the course
A lecture and work in small groups at the beginning of the course provides guidance on accessing the scientific literature and writing essays, and advice on careers.
About 100 lectures are provided, divided between Systems Pharmacology, and Molecular and Cellular Pharmacology. The groupings are more administrative than real: there is a seamless continuity between molecular mechanisms and the higher order levels of biological organisation. Lectures are timetabled to allow you to attend them all. With no more than 2+ hours/day spent in lectures, there is plenty of time to explore specific topics in considerable depth through the primary literature. There is some weighting of lectures towards the Michaelmas Term (when there are sometimes two lectures/day). This leaves more time in the Lent Term (usually 1 lecture/day) for projects and dissertations. As with most Part II courses, there are no Saturday lectures. You can expect to encounter the most recent research and the controversies surrounding it. The lectures shown are typical, but each year there are some changes to accommodate staff changes, sabbatical leave, etc.
Pharmacology of transporting epithelia (4 lectures)
Structure and function of epithelia and mechanisms of transepithelial ion transport. Drugs and hormones that stimulate ion transport. Ion channels, ion pumps and cotransporters with a focus on cystic fibrosis transmembrane conductance regulator. Therapeutic strategies for cystic fibrosis and its pharmacological treatment.
Cardiovascular pharmacology (6 lectures)
Nitric oxide: its identification and roles in the vasculature, hypercholesterolaemia and atherosclerosis. Endothelium-dependent hyperpolarisation (EDH). NO as a hyperpolarising agent. The role of ion channels, possible factors mediating EDH. Cannabinoid actions on the cardiovascular system.
Cholesterol and diabetes (6 lectures)
Cellular and systemic mechanisms involved in control and use of blood lipids. Their involvement in hypercholesterolaemias and other lipid disorders related to increased risk of cardiovascular disease. The relation between blood lipids, type II diabetes mellitus and obesity. Metabolic syndrome. Drugs and therapeutic targets.
Neurocircuitry regulating satiety (4 lectures)
Neurocircuitry regulating satiety, including the serotonergic, catecholaminergic and primary neuropeptide pathways. Use of lesions, pharmacological, behavioural, neuroanatomical and genetic approaches.
Pancreatic islet and gut hormones (3 lectures)
Cell biology of endocrine cells in the pancreas and intestine that are involved in glucose homeostasis and appetite control, and how they can be targeted therapeutically for treatment of diabetes and obesity.
Inflammation and angiogenesis (6 lectures)
Role of vascular endothelial cells in inflammation, immune responses and angiogenesis, as the basis of novel therapeutic approaches and drug discovery.
Circadian Rhythms in Pharmacology (3 lectures)
Biological clocks in every cell keep time and orchestrate cellular physiology on a daily time base. In this short lecture course, we will discuss the processes that are regulated by the clockwork at the cell and tissue levels, and how this impacts on drug metabolism and toxicity. We will also consider how knowledge of the body's internal timing can be used to maximise efficacy and minimise toxicity of drugs.
Pharmacology of Psychiatric Disorders (4 lectures)
The genetic, neurobiological and environmental contributions to several major psychiatric illnesses with particular emphasis on the therapeutic mechanisms of psychotropic medications.
Drug discovery (3 lectures)
How are lead compounds identified and developed, and then brought through clinical trials to treat human and animal diseases?
Stem cells (4 lectures)
Molecular and Cellular Pharmacology
Signalling by cyclic AMP (5 lectures)
Synthesis and degradation of cAMP, and its downstream targets: protein kinase A, cyclic nucleotide-gated channels and EPAC. The subcellular organization of cAMP microdomains: how are these organized and addressed experimentally?
G protein-coupled receptors and G proteins (5 lectures)
G protein-coupled receptors (GPCR) are the most common receptors and the largest category of drug targets. Structural basis of GPCR and G protein activation and its exploitation to develop new drug targets. What is an active G protein? How do GPCR catalyse G protein activation? How do cells regulate the lifespan of active G proteins? How is specificity maintained? How can the same receptor selectively interact with many signalling pathways?
Ca2+ signalling (4 lectures)
How is Ca2+ transported across membranes by pumps and channels? How do extracellular signals regulate Ca2+ transport across the plasma membrane and the membranes of intracellular organelles? How does the spatial and temporal complexity of intracellular Ca2+ signals allow Ca2+ reliably to regulate diverse cellular processes?
Ca2+ signalling in the heart (3 lectures)
Ca2+ stimulates contraction of cardiac myocytes during every heart-beat and the activity of genes involved in hypertrophic remodelling during periods of increased haemodynamic demand. How are Ca2+ signals generated and interpreted to control contractility and gene transcription?
Adipose tissue development and function (4 lectures)
What do fat cells do and why is metabolically active adipose tissue critical for human health? What are the pathways and molecules controlling the formation of new adipocytes from stem cells? How do defects in these pathways cause human disease and how may these pathways be targeted to treat metabolic disease?
Inositide signalling (5 lectures)
Regulation of phospholipases C. Functions of higher inositol phosphates. Regulation of synthesis and removal of phosphatidylinositol 3,4,5-trisphosphate (PIP3) and its functions. Structural basis of PIP3 functions in the context of cancer and inflammation.
Voltage-gated ion channels (5 lectures)
Voltage gated ion channels: structure, function and regulation in the nervous system. Diversity of ion-selective channels, structural basis for the diversity, and the role of channels in determining electrical firing properties of neurons and in regulating synaptic transmission. Molecular mechanisms of voltage-dependent gating and of the pore in permeation and selectivity.
Synaptic mechanisms (6 lectures)
Molecular mechanisms underlying regulated exocytosis, with particular reference to neurotransmitter release. Methods used to identify the molecular players, the assays used, how the molecules interact, development of approaches that allow detection of individual vesicle fusion events, and information arising from these approaches. Endocytotic recapture of membrane after vesicle fusion.
Nociception (4 lectures)
Transduction, adaptation and sensitization in the context of pain. The molecular basis of excitation of nociceptors. Short-term sensitization of nociceptive nerve terminals. Longer-term processes involved in sensitization. Neuropathic pain.
Glutamatergic transmission (5 lectures)
Glutamate as a neurotransmitter in the CNS, with emphasis on the hippocampus, cerebellum and brainstem. The postsynaptic response to glutamate mediated by AMPA, kainate, NMDA and metabotropic receptors. Glutamate transport by plasma membrane and vesicular transporters.
Cys-loop family of ligand-gated ion channels. (3 lectures)
Structure and function of this major family of ligand-gated ion channels, typified by nicotinic acetylcholine receptors. Methods used to relate structure to function. GABAA receptors as important drug targets.
Molecular aspects of multidrug transport (5 lectures)
Molecular basis of multidrug specificity by multidrug transporters in bacteria and human cells. Mechanisms of drug translocation and of modulators that inhibit multidrug transport . Use of nutrient uptake systems in drug delivery of hydrophilic prodrugs.
There are 8 tech talk sessions, some of which cover more than one topic. They are delivered weekly in the Michaelmas Term and aim to provide a comprehensive overview of a wide variety of advanced techniques currently used in pharmacology research. They are usually delivered by senior research fellows with first-hand expertise in the techniques they discuss. Tech talks provide essential background to critical evaluation of materials presented in lectures, and are thereby an essential and integral part of the core course. For Part II students, they additionally provide a foretaste of techniques that may be encountered in research projects. Topics, which may vary between years, have recently included:
- Molecular biology
- Protein expression and detection
- Protein purification and reconstitution
- Biophysics and structural analysis
- Imaging applied to cell signalling
- siRNA and transgenics
- Behavioural techniques
You will be allocated to a discussion group of about 10 students with 2+ teaching staff as soon as you join the department. Early in each term, you will agree a timetable for your meetings and you are then expected to attend all meetings of the group. The exact format of the meetings varies between groups, but each seeks to develop presentation skills and the ability critically to evaluate the scientific literature.
We attach considerable importance to supervisions: all lecturers in the Part II course are required to provide supervisions. Supervisions are likely to be in larger groups than at Part I, but they will almost invariably be given by the person who delivered the lectures. Lecturers will also mark essays. The onus rests more with you than at Part I to arrange supervisions: most lecturers provide a sign-up sheet.
These are held weekly during term and comprise a mix of external and internal speakers talking about their recent research. They are followed by drinks and nibbles; providing a relaxed chance to catch up with the speaker and everyone else in the department.
The list of projects is issued in early November. Over a few days, each project supervisor is then available to discuss potential projects. The allocation of students to projects is left entirely to the Part II class. Most projects are within the research labs of staff of the department, but a few projects are based elsewhere (e.g., Clinical Pharmacology). You will spend about 3 days/week working on your project (24 days in total). Many students find this to be the most rewarding part of the course, and it is not uncommon for work arising from a Part II project to be published or presented at scientific meetings. Several former students have won national prizes for their projects. For students contemplating a research career, this may be the first real taste of what it involves. The project is submitted as a written report (in the style of a published paper) and presented as a talk to the entire department in Easter Term. Recent project titles include:
- Oxidative-stress induced changes in ABC efflux transporters in brain endothelium
- Actions of nitric oxide-releasing non-steroidal anti-inflammatory agents on smooth musclee
- Actions of prostaglandins on vascular smooth muscle in ruminants
- Urotensin-II in human heart failure
- Functional connectivity of the amygdala and lateral hypothalamus
- Characterisation and isolation of acid-sensing ion channels
- Optimization of fluorescent cAMP sensors for single-cell imaging
- Neuroendocrinology of food intake, body weight, and glucose homeostasis
- Visualising DNA interactions by atomic force microscopy
- Vasorelaxant effects of long-chain fatty acid ethanolamines
- Expression of GFP-tagged proteins in the chick nervous system
- Cellular and molecular basis of magnetoreception in animals
- Lysosomal Ca2+ uptake mechanisms.
- Simulation of the uptake of quinoline antimalarials into P. falciparum
- Interaction of PH domains with inositol lipids
- Location, activity and function of type II PI5P 4-kinase
- Interactions of WNK proteins and CFTR in normal and transgenic mice
- Trafficking of TRPV1
- DNA origami
- Genomic tagging of inositol lipid kinases
- MRI imaging of neurotoxic lesions in mice
- Targeting of P2X purinoceptors
- The role of WNKs in the regulation of renal Na+ transport
- Expression of a protein-based Ca2+ indicator in the ER
- Ca2+ signals evoked by different receptors in HEK cells
- IP3 interactions with the N-terminal of its receptor
- Interactions of bacterial ABC transporter with antibiotics and toxins
- Multidrug resistance of the pathogen Pseudomonas aeruginosa
- Real-time imaging of cAMP and Ca2+ in GIP-secreting cells
- Roles of IP3 receptors in migration of glioblastoma cells
- Effects of flavanoids on CFTR-mediated Cl- secretion in murine colon
Dissertations (BBS only)
You will select a dissertation title from lists provided by both your Major and Minor Subjects; most of our students choose a title from the pharmacology list. Prospective supervisors will be available to discuss titles before you make the final decision. You will meet, probably about 4 times during the Lent Term, with your dissertation supervisor, who will provide guidance on your dissertation topic. The dissertation provides an opportunity to explore a single area in considerable depth. Recent titles from pharmacology include:
- The involvement of reactive oxygen species in events in brain vasculature following stroke
- Wnt signalling pathways in vascular endothelium
- The mechanism of neuronal death following brain anoxia/ischaemia
- Recycling and replenishment of presynaptic glutamate
- Mechanism and therapeutic implications of adrenergic receptor desensitization
- The significance of receptor dimerization
- Cell-free reconstitution of membrane fusion
- The properties of the exocytotic fusion pore
- How do neuromodulators stimulate and suppress appetite?
- Identifying brain serotonin neurons that may be targeted to control body weight
- TRPV1 channels in vascular control
- Gap junctions and cardiovascular disease
- Epithelial diseases: causes and treatments
- The role of CFTR as a modulator of airway inflammation
- Sleep and circadian abnormalities in neurological disease
- Protein aggregation in Alzheimer’s disease
- Channelopathies: ion channel defects linked to heritable clinical disorders
- Assembly and targeting of ligand-gated ion channels
- How does the hypothalamus integrate stress, motivation and reward?
- New molecular targets in the treatment of anxiety
- Corticotrophin-releasing factor signalling as a target to treat CNS disorders
- Intracellular Ca2+ channels
- Ca2+ and disease
- Role of multidrug transporters in drug resistance of pathogenic micro-organisms
- Mechanisms of ATP binding and hydrolysis in ATP-binding cassette transporters
- Ca2+ entry
Minor Subject (BBS only)
Detailed arrangements for the minor subjects differ between subjects. You can obtain further details from the web site and from the course booklet for BBS. The timetables below do not include the minor subject details.
There are 4 written papers in Pharmacology. Each paper carries equal marks. All 4 papers are taken by all candidates from BBS and Part II Pharmacology. For Part II Pharmacology students, the research project contributes 20% of the total mark. For BBS students, the dissertation and Minor Subject paper contribute with the marks from the 4 written papers to the final mark. All BBS candidates have an oral examination on the subject of their dissertation. The examiners may also invite candidates from either course for an oral examination on any part of the course. There is no written practical examination for either course.
The academic year
|Study Skills||An introduction, via a lecture and in small groups, to handling the scientific literature.|
|Lectures||Usually 2+ each day (usually 9am, and 10am or 11am). Monday to Friday.|
|Tech Talks||Weekly throughout term.|
|Discussion Groups||4 meetings. These are likely to focus on the presentation and critical evaluation of published papers.|
|Supervisions||Arranged individually. All lecturers are available to provide supervisions. They are often in larger groups than at Part I, and usually a week or two after relevant lectures to allow time for additional reading.|
|Preparing for Projects and Dissertations||Session at the end of term providing guidance on projects (including health and safety) and BBS dissertations. All students must attend.|
|Tea Talks||Weekly at 4pm on Fridays, followed by wine and nibbles.|
|Lectures||1 (or sometimes 2) each day, usually at 9am. Monday to Friday.|
|Discussion Groups||4 meetings. These are likely to combine presentations with reviews of progress in projects or dissertations|
|Research Project||Pharmacology Part II only. About 24 days spent completing and writing a practical research project. You will meet regularly with your research project supervisor throughout the term.|
|Dissertation||BBS only. You will have the entire term to complete your dissertation, supplemented by about 4 formal meetings with your dissertation supervisor.|
|Supervisions||As in Michaelmas Term.|
|Practical Statistics||Workshops at the beginning of term designed to help with data analysis during research projects. Compulsory for Part I, optional for BBS.|
|Tea Talks||Weekly at 4pm on Fridays, followed by wine and nibbles.|
|There is no formal teaching in the Easter Term, leaving you free to read and revise.|
|Research Projects||Pharmacology Part II only. You will present your research project as a 10-minute talk to the department at the all-day research seminars session. The talk is assessed.|
|Examinations||These are scheduled in the second half of term.|
The maximum number of students allowed onto the Part II Pharmacology course is 30, and determined by the number of research projects available. Our selection policy is to accept students with the best overall marks in Part IB examinations. Where necessary, the mark in Part IB Pharmacology or MODA serves as a tie-breaker. Students from MVST and NST are treated identically. For admission to the BBS course, students will be expected to have an adequate background in pharmacology evident from performance in MODA or Part IB Pharmacology. There are up to 20 places for BBS Pharmacology. There are no interviews and no application need be made other than on the list of Part II preferences submitted through your College. Prospective applicants are invited to contact Professor Taylor or any of the teaching staff if they have any queries about the courses.