Biomedical Science with a Sandwich Year - BSc (Hons)

This course will provide an introduction to biomolecules in living matter. The simplicity of the building blocks of macromolecules (amino acids, monosaccharides, fatty acids and purine and pyrimidine bases) will be contrasted with the enormous variety and adaptability that is obtained with the different macromolecules (proteins, carbohydrates, lipids and nucleic acids). The nature of the electronic and molecular structure of macromolecules and the role of non-covalent interactions in an aqueous environment will be highlighted. The unit will be delivered though lectures, practicals, workshops and small group teaching. Frequent feedback will be given to the students to ensure that they fully understand what is expected of them. Short tests will be used throughout the unit to test the students' knowledge and monitor that the right material has been extracted from the lectures.



Lectures:



Introduction. What is Biochemistry? The chemical elements of living matter. The central role of carbon and the special properties of water. The underlying principle in the use of monomers to construct macromolecules. The nature of weak interactions in an aqueous environment.

Nucleic Acids. Types - DNA and RNA. Chemical structure, properties of phosphodiester linkage, primary structure. Nucleic Acids. Secondary structure - Watson Crick DNA model, A and Z DNA. Tertiary structure - circular DNA, supercoiling. Stability of nucleic acids - sugar phosphate chain, base pairing, base stacking. Biological functions of Nucleic Acids. Overview of replication, transcription and translation. Role of RNA - types, post-transcriptional processing, tRNA structure, ribosomes.

Proteins. Amino acids - structure, classification, properties. Peptides and peptide bond. Secondary structure. Structural proteins. Tertiary structure - role in function. Factors determining secondary and tertiary structure. Quaternary structure. Protein Function - Myoglobin versus Haemoglobin. Haemoglobin variants. Subcellular fractionation. Protein isolation and purification. Use of Molecular Graphics packages.

Carbohydrates. Monosaccharides, stereoisomers, conformation, derivatives. Disaccharides, glycosidic bond stability and formation (a and ß). Polysaccharides. Storage (e.g. starch, glycogen), structural (e.g. cellulose, chitin, glycosaminoglycans bacterial cell walls). Glycoproteins.

Lipids: lipids, fatty acids, triacylglycerols, glycerophospholipids, sphingolipids, glycosphingolipids, steroids, waxes. Membranes: lipid bilayers, hydrophobic effect, fluid-mosaic model, membrane-bound proteins. Membrane transport systems: passive transport, ionophores, active transport, double-membrane systems, porin.

General techniques in biomolecular science: spectroscopy of small molecules, chromatography and electrophoresis.



Practicals:



1. Preparation and identification of nucleic acids.

2. Protein characterisation - spectroscopy, DTNB and disulphide bonds.

3. Analysis of the sugar composition of honey and TLC separation of lipids.

4.. Chromatographic separation of proteins

5. Assessed practical.



Workshops:



1. Molecular modelling using Jmol or similar

2. Model building workshop mono and di saccharides

Credits: 15 credits (7.5 ECTS credits).

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This course aims to introduce the 'workers' present in all cells – enzymes, and their role in the chemical reactions that make life possible.



The fundamental characteristics of enzymes will be discussed – that they are types of protein that act as catalysts to speed up reactions, or make unlikely reactions more likely. Methods for analysis of enzymic reactions will be introduced (enzyme kinetics). Control of enzyme activity, and enzyme inhibition will be discussed.



Following on from this the pathways of intermediary metabolism will be introduced. Enzymes catalyse many biochemical transformations in living cells, of which some of the most fundamental are those which capture energy from nutrients. Energy capture by the breakdown (catabolism) of complex molecules and the corresponding formation of NADH, NADPH, FADH2 and ATP will be described. The central roles of the tricarboxylic acid cycle and oxidative phosphorylation in aerobic metabolism will be detailed. The pathways used in animals for catabolism and biosynthesis (anabolism) of some carbohydrates and fat will be covered, as well as their control. Finally how humans adapt their metabolism to survive starvation will be discussed.

Credits: 15 credits (7.5 ECTS credits).

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This course will expose students to key themes and experimental techniques in molecular biology, genetics and eukaryotic cell biology illustrated by examples from a wide range of microbial and mammalian systems. It will cover basic cell structure, and organisation of cells into specialised cell types and complex multi-cellular organisms. The principles of the cell cycle and cell division will be outlined. The control of all living processes by genetic mechanisms will be introduced and an opportunity to handle and manipulate genetic material provided in practicals. Lectures and practicals will run concurrently as far as possible and monitoring of students' knowledge and progress will be provided by multiple-choice tetsing and feedback in workshops.



Lectures:



Functional Geography of Cells: Introduction to Cell Organisation, Variety and Cell Membranes. Molecular Traffic in Cells. Organelles involved in Energy and Metabolism. Eukaryotic Cell Cycle. Chromosome Structure & Cell Division. Meiosis and Recombination.



Molecular biology: The structure and function of genetic material. Chromosomes, chromatin structure, mutations, DNA replication, DNA repair and recombination, basic mechanisms of transcription, mRNA processing and translation.



Techniques in Molecular and Cellular Biology: Methods in Cell Biology - light and electron microscopy; cell culture, fractionation and protein isolation/electrophoresis; antibodies, radiolabelling. Gene Cloning – vectors, enzymes, ligation, transformation, screening; hybridisation, probes and blots, PCR, DNA sequencing. Applications including recombinant protein expression, trangenics/knockouts, RNAi, genome projects, DNA typing, microarray and '…omics' studies (genome, proteome, interactome, metabolome etc).



Practical: Restriction digestion of DNA and gel analysis

Credits: 15 credits (7.5 ECTS credits).

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This module considers the anatomy and function of normal tissues, organs and systems and then describe their major pathophysiological conditions. It will consider the etiology of the condition, its biochemistry and its manifestation at the level of cells, tissues and the whole patient. It will cover the diagnosis of the condition, available prognostic indicators and treatments.



It will include:



Cells and tissues, membrane dynamics, cell communication and homeostasis; Introduction to the nervous system; The immune system and inflammation; Blood cells and clotting; The cardiovascular system; the respiratory system; The digestive system, liver and pancreas and the Urinary system.

Credits: 15 credits (7.5 ECTS credits).

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Subject-based and communication skills are relevant to all the bioscience courses. This module allows you to become familiar with practical skills, the analysis and presentation of biological data and introduces some basic mathematical and statistical skills as applied to biological problems. It also introduces you to the computer network and its applications and covers essential skills such as note-taking and essay writing.



Topics covered in lectures/workshops:



How biosciences is taught at UKC - lectures, supervisions, problem solving classes, practicals. Effective study and listening skills, note taking and use of the library. Support networks.

General principles of analytical biochemistry - quantitative/qualitative analysis, making and recording measurements. The quality of data - random and systematic error, precision, accuracy, sensitivity and specificity.

The manipulation and presentation of data - SI units, prefixes and standard form

Molarities and dilutions -concentration (molarity) and amounts (moles), dilutions.

Acids, bases and buffers in aqueous solutions - Definition of pH, acid and bases (including a revision of logarithms). Acid-base titrations. Buffer mixtures, buffering capacity and the Henderson-Hasselbalch equation.Dissociation of polyprotic, weak acids. Biochemical relevance of pH e.g. pH dependant ionisation of amino acids.

Spectroscopy - The range of electromagnetic radiation. Absorption and emission of radiation. Molecular absorptiometry - the use of the Beer-Lambert relationship for quantitative measurements using absolute or comparative methods (molar and specific extinction coefficients).

Reaction Kinetics. Reactions and rates of change: Factors affecting the rate of a reaction. Zero, first and second order reactions. Rate constants and rate equations (including integration). Worked examples of rates of reactions.



Statistics Descriptive statistics: definition of statistics, sampling, measurement scales, data hierarchy, summarising data, averaging, mean, mode, median, quantiles, graphical methods, displaying proportions, charts and chart junk. Parametrising distributions: coefficient of variation, normal distribution, properties of the normal curve, skewness and kurtosis, accuracy and precision.

Probability: definition, events, exclusivity and conditional probability, throwing dice and tossing coins, independent and dependent events, permutations, multiplicative rule, binomial distribution, unequal probabilities, Pascal's triangle, factorials and combinations.

Hypothesis testing: null hypothesis, p-value, normal curve, z-score and t-score, t values and confidence interval, t-tables, comparing two samples, degrees of freedom, t-tests for same and different sample sizes, paired samples, difference between means.

Correlation and covariance: two-dimensional distributions, scatter diagram, degree and limits of correlation, spurious correlation, correlation and causality, time correlation, normalising the covariance, covariance in spreadsheet calculations.

Regression: the regression line, slope and intercept parameters, regression in spreadsheet calculations, history of regression, assumptions in regression, effect of outliers, how not to use statistics.





Practicals:



1. Introduction to basic laboratory techniques-

a) preparation of buffer solutions and

b) determination of accuracy

2. pH and buffers

3. Colorimetry and Spectrophotometry

Credits: 15 credits (7.5 ECTS credits).

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The principles of chemistry are an essential foundation for biochemistry. Building up from the atomic level, this module introduces periodicity, functional groups, compounds and chemical bonding, molecular forces, molecular shape and isomerism, and chemical reactions and equilibria, enabling you to understand the importance of organic chemistry in a biological context.



Phase A: Autumn Term (5 x 2 hr Workshop)



Basic chemical concepts for biology will be taught and applied through examples in a workshop atmosphere. The five workshop topics covered are: (i) Atoms and states of matter (ii) valence and bonding (iii) basic organic chemistry for biologists (iv) molecular shapes and isomerism in biology and (iv) chemical reactivity and chemical equations.



Assessment feedback of basic chemistry (1 session/lecture)



Phase B: Autumn Term (8 lectures, 1 x 2 hr Workshop)



Chemical and biochemical thermodynamics (6 lectures, 1 workshop). Topics covered are: (i) energetic and work, (ii) enthalpy, entropy and the laws of thermodynamics (iii) Gibbs free energy, equilibrium and spontaneous reactions, (iv) Chemical and biochemical equilibrium (including activity versus concentration and Le Chatelier's principle). The two hour workshop is designed to be delivered as small group sessions to cover the applications and practice of thermodynamics concepts.



Chemistry applied to biological concepts (2 lectures): bonding, valence, hybridisation as well as biological applied thermodynamic process (biomolecular association/dissociation).



Phase C: Spring Term (15 lectures, 1 x 2 hr Workshop)



Fundamental organic chemistry with biological examples. Topics covered:(each being 1 lecture unless stated): (i) Introduction and basic functional chemistry, (ii) Isomerism and stereochemistry - 2 lectures (iii) Reaction mechanisms - 2 lectures (iv) Alkanes/alkyl halides/alkenes/alkynes - 2 lectures (v) Aromatic compounds - 2 lectures (vi) Heterocyclic compounds (vii) Amines and alcohols (viii) Carbonyl compounds and carboxylic acids - 3 lectures and (ix) Biological inorganic chemistry. The two hour workshop is designed to be delivered as small group sessions to cover the applications of reaction mechanisms and reaction schemes.



Phase D: Spring Term (8 lectures, 1 x 2 hr Workshop)



Advanced topics for A2 Chemistry entrants for Biochemistry and Biomedical Science. Topics covered: (i) Uses of spin-resonance spectroscopies in Biology - 3 lectures (ii) Proteins and Amino Acid Chemistry in enzymes - 1 lecture (iii) Chemical Biology concepts: Globins:structure/function, sugars and phosphates, metabolism and biochemistry of Glucose, nucleotides and nucleic acid chemistry - 4 lectures.

Credits: 30 credits (15 ECTS credits).

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This module is an introduction to Mendelian genetics and also includes human pedigrees, quantitative genetics, and mechanisms of evolution.



Lectures/Workshops:



Genetics

An introduction to the genetics of a variety of organisms including Mendelian inheritance (monohybrid and dihybrid) and exceptions to the predicted outcomes due to incomplete dominance, co-dominance, lethal alleles, epistasis and genetic linkage, the chromosomal basis of inheritance, organelle based inheritance and epistasis. The inheritance of human genetic disease and its investigation by human pedigree analysis will also be introduced. Bacterial genetics.



Evolution

The nature of mutation, including molecular mechanisms leading to the mutation of DNA, and the role of both mutation and horizontal gene transfer in evolution. Historical views on evolution, Darwin’s observations, the fossil record to modern techniques. Microevolution, population genetics and analysis of the distribution of genes within populations and mechanisms of gene flow, genetic drift, selection and speciation.

Credits: 15 credits (7.5 ECTS credits).

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This module develops a more detailed understanding of particular physiological systems and relates this to relevant disease processes and their detection. The role of research and laboratory methods in understanding human disease is also introduced at this stage.



Lecture Overview



Reproductive System: Male and female reproductive systems; Endocrine control of reproduction: Fertilisation; Early embryogenesis; Pregnancy and Parturition; Reproductive disorders



Muscle: Muscle types: skeletal, smooth and cardiac; Structure of muscle; Molecular basis of contraction; Regulation of contraction including neural control; Energy requirements of muscle; Types of movement: reflex, voluntary, rhythmic; Muscle disorders.



Nervous System Cells of the nervous system: neurons and glia; Electrical properties of neurons: action potential generation and conduction; Synaptic structure and function: transmitters and receptors. Structural organization of the central nervous system (CNS) and function of individual regions; Organization and function of the peripheral nervous system (PNS): somatic motor, autonomic (sympathetic and parasympathetic) and sensory; Sensory systems: vision, hearing, taste, smell, pain. Disorders of the nervous system



Endocrine System: Endocrine glands; Classes of hormones; Mechanisms of hormone action; Regulation of hormone release; Endocrine disorders.

Credits: 15 credits (7.5 ECTS credits).

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This module introduces you to the major concepts underpinning pharmacology – the study of drugs and their actions in cells, tissues and whole animals. You learn to describe the effects of drugs in cells and to relate the mechanism of drug action to their therapeutic intervention in disease.



A synopsis of the curriculum

Pharmacodynamics and chemical transmission

• Introduction and basic principles of drug action

• Structure and function of receptors and ion channels

• Neurotransmission. Neurons and synapses, neuromuscular junctions, autonomic nervous system, adrenergic and cholinergic nerve terminals, neuromodulation

• Local transmission. Inflammatory response: role of histamine

Systematic pharmacology

• The Cardiovascular System. Regulation of blood pressure, angina and cardiac failure

• The Respiratory System. Pathogenesis of asthma, mode of action of bronchodilators and anti-inflammatory agents

• The Central Nervous System -Central neurotransmitters and opioids, Local and general anaesthetics, Treatment of anxiety and sleep disorders, Treatment of schizophrenia, Parkinson's disease and mania/depression, Drugs of abuse and withdrawal symptoms

• The Gastrointestinal Tract. Pathogenesis and treatment of peptic ulcers, constipation and diarrhoea.

• The Endocrine and Reproductive Systems. Corticosteroids, contraception and pregnancy, treatment of subfertility

• Chemotherapy. General principles of antibiotic/antiviral/antifungal/anticancer agents





Practical workshop:

Drug receptor binding data analysis

Credits: 15 credits (7.5 ECTS credits).

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This module describes how errors in metabolic processes result in the development of human diseases such as phenylketonuria, gout, hypercholesterolarmia, diabetes and porphyria.



Topics:



Introduction: Revision of metabolism taught previously.



Overview of inherited metabolic disease processes: Accumulation of substrate; Accumulation of a normally minor metabolite; Deficiency of product; Secondary metabolic phenomena. Relation to genetics: Autosomal recessive disorders; X-linked recessive disorders; Autosomal dominant disorders;



Electron transport and oxidative phosphorylation in mitochondria. The chemiosmotic hypothesis. Ragged red fibre mitochondrial myopathies



Human metabolism in relation to the Nitrogen cycle

The urea cycle: diseases associated with enzyme deficiencies.

Metabolism of amino acids and nucleotides: diseases including phenylketonuria and gout.



Vitamins and malnutrition



Biosynthesis of cholesterol: familial hypercholesterolemia and atherosclerosis.



Sugar metabolism: Glucose transporters and disease; Glycogen storage disease; Pyruvate dehydrogrenase complex defects.



Diabetes and insulin: diabetic ketoacidosis.



Heme synthesis and breakdown in health and disease: Metabolic defects in heme synthesis and the porphyrias.



Cancer: metabolic adaptations and relation to chemotherapy.

Credits: 15 credits (7.5 ECTS credits).

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This module will introduce the student to two of the four main branches of laboratory medicine, Clinical Biochemistry and Cellular Pathology, and begin to develop the skills students will require to work effectively and safely within a clinical setting.

Clinical Biochemistry

1. The use of the laboratory, quality assurance and techniques (including Instrumentation and Automation, Clinical Applications, Antigen-Antibody Reactions, Separation techniques) will be introduced using the various screening and testing procedures as below.



2. Screening for disease – concepts, rationale and screening programmes, application of biochemical techniques to paediatrics and inborn errors of metabolism, tumour markers, liver function, iron and porphyrias, enzymes and their use in laboratory medicine, clinical applications of protein biochemistry, nutrition in health and disease, lipids and atherosclerosis.



Cellular Pathology

1. Application of histological and cytological techniques in a clinical setting including cell and tissue sampling techniques for histological and cytological diagnosis;

2. Use, histochemical and immunohistochemical stain techniques for diagnosis and selection of treatment.

3. Microscopic methods used in cellular pathology

4. Quality control and quality assurance

Credits: 15 credits (7.5 ECTS credits).

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A. Communication Skills in Biosciences:

Essay writing, oral presentations, laboratory reports, the scientific literature and literature reviews. Working in groups.



B. Techniques in Biomolecular Science:

Immunochemistry. Monoclonal and polyclonal antibody production, immuno-chromatography, ELISA and RIA.

Electrophoresis, Immunoblotting, Protein Determination, Activity Assays, Purification



C. Computing for Biologists:

Bioinformatics, phylogenetic trees, database searches for protein/DNA sequences



D. Mini-project – introduction to research skills:

Students will work in groups of eight to undertake directed experimental work (Group Project) before extending the project further through self-directed experiments working as a pair (Mini Project).



E. Careers:

The programme will be delivered by the Careers Advisory Service and will review the types of careers available for bioscience students. The sessions will incorporate personal skills, careers for bioscience graduates, records of achievement, curriculum vitae preparation, vacation work, postgraduate study, interview skills and action planning.

Credits: 15 credits (7.5 ECTS credits).

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This module describes the integration of the many chemical reactions underpinning the function of cells. For example, how cells make ATP and use it to drive cellular activities, and how plant cells harvest energy from the sun in the process of photosynthesis.



Part A: principles of metabolic regulation

Metabolic regulation maintains molecular homeostasis. Metabolic controls that lead to changes in output of metabolic pathways in response to signals or changes in circumstances.

Common points of regulation: reactions far from equilibrium. Examples from carbohydrate metabolism of relationship between equilibrium constants, mass action coefficients and free energy changes.

Metabolic control analysis

Mechanisms of regulation: examples from e.g. carbohydrate metabolism. Timescale; transcriptional regulation; post-translational modification; signalling via e.g. Ca2+ and metabolites especially AMP.



Part B: plant metabolism

Photosynthesis

C3 and C4 pathways

Glyoxylate cycle

Secondary metabolites: morphine, quinine, nicotine, caffeine and others



Part C: microbial metabolic adaptations

Microbial genomics: analysing metabolic pathways using genomic information

Microbial metabolism in the nitrogen cycle

Examples of specialised metabolism: Salmonella, Campylobacter and others

Secondary metabolites: certain antibiotics



Part D: metabolism in biotechnology

Manipulating microbial metabolism for the production of useful compounds: citric acid, amino acids etc.

Manipulating mammalian cell metabolism in biotechnology: production of complex molecules by animal cells in culture, and its relation to metabolic processes.

Credits: 15 credits (7.5 ECTS credits).

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The module deals with the molecular mechanisms of gene expression and its regulation in organisms ranging from viruses to man. This involves descriptions of how genetic information is stored in DNA and RNA, how that information is decoded by the cell and how this flow of information is controlled in response to changes in environment or developmental stage. Throughout, the mechanisms in prokaryotes and eukaryotes will be compared and contrasted and will touch on the latest developments in how we can analyse gene expression, and what these developments have revealed.



Lectures:

A. The genome - Human genome, human chromosomes, mapping and cloning human genes, DNA testing and disease diagnosis, genome organisation, analysing genomes.

B. The gene - Gene organisation. Gene evolution. Gene transcription in prokaryotes and eukaryotes: RNA polymerases, promoters, regulatory sequences. mRNA processing in eukaryotes: intron splicing, the spliceosome, turnover pathways, catalytic RNA. mRNA translation: tRNA, the ribosome, mechanism (initiation, elongation, termination).

C. Gene regulation - Transcriptional regulation in prokaryotes: operons. Transcriptional regulation in eukaryotes: simple vs complex systems, promoters and enhancers. Post-transcriptional regulation: mRNA processing and turnover, translational control, non-coding RNAs. Epigenetic control.

Credits: 15 credits (7.5 ECTS credits).

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A placement typically is a 9-12 month internship with a commercial or public sector or charity organisation which provides opportunities for the student to develop graduate level subject-specific and generic employability skills. Choice of placement by student will be guided and facilitated at UoK with the learning outcomes listed above in mind. It is requested by UoK that the student be closely guided in work (usually with a named supervisor) involving specialist training. Placements are expected to have a scientific research focus and incorporate a project element that may be written up as a scientific report, however, the specific type of work undertaken may vary significantly from placement to placement. The research project should occupy not less than thirty percent of the sandwich year.

Credits: 120 credits (60 ECTS credits).

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You study the molecular basis for microbial pathogenesis in relation to bacterial, viral and fungal pathogens. Topics include host-pathogen interactions, therapeutic strategies, vaccination and the role of viruses in the development of cancer.



Lectures:



Bacterial pathogens



Microbial pathogenicity: variations on a common theme.

Methodology of studying bacterial pathogenesis.

Virulence factors including toxins and adhesins.

Mechanisms of Pathogenesis.

Applications of virulence factors in the treatment and prevention of disease.



Viral pathogens



Viruses and Human Disease - transmission and spread, overview of important human virus infections, mechanisms of transmission (Aerosol, Oro-fecal, Sexual etc.), epidemiology - patterns of endemic and epidemic disease.



Mechanisms of Pathogenesis - spread in the body, disease mechanisms, mechanisms of cell killing (Herpes simplex and Polio), immunopathology and auto-immune disease.



Virus infection – long term consequences for the host, escape through mutation and natural selection, disabling the immune system, avoidance mechanisms.



Viruses and Cancer - mechanisms of virus transformation (EBV, Retroviruses & Papilloma), viruses and human cancer (Cervical carcinoma, Hepatocellular Carcinoma & Burkitt Lymphoma).



Human fungal pathogens



Fungi and Human Disease - overview of major human fungal infections, clinical picture, diagnosis and mechanisms of transmission, epidemiological aspects of fungal infections.



Mechanisms of Pathogenesis - adherence, invasion of eukaryotic cells, morphogenesis, virulence factors: Candida albicans, Aspergillus fumigatus, Cryptococcus neoformans, Histoplasma capsulatum.



Whole genome analysis of fungal pathogens



Host resistance to infection and antifungal chemotherapy - host defense mechanisms to fungal infections, role of the humoral and cellular immune response, antifungal chemotherapy: azoles, polyenes, echinocandines and antimetabolites, future developments for the treatment of fungal infections.



Eukaryotic pathogens (parasites)



Parasites and pathogenicity, transmission and diversity.



Definitions on parasitic lifestyle.



Investigations on worldwide parasitic outbreaks (e.g. malaria, trypanosomiasis, cryptosporidiosis) and their socio-economical effects.

Credits: 15 credits (7.5 ECTS credits).

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This module describes the anatomy, physiology, pathology, and therapy of the blood and blood forming tissues, including the bone marrow. It covers a wide range of disorders including haematological malignancies, infection with blood-borne parasites that cause malaria, and inappropriate clotting activities such as deep vein thrombosis.



Lectures:



Haematology:



An introduction to haematology: module outline, aims and objectives.

Haemopoiesis and the bone marrow.



The red cell: structure and function.

Inherited abnormalities of red cells.

Anaemias - acquired and inherited.



White blood cells in health and disease.

An introduction to haematological malignancies.

Bleeding disorders and their laboratory investigation.

Thrombophilia.

Blood borne parasites.



Blood Transfusion:



The ABO and Rhesus blood group systems.

Other blood group systems.

Blood banking techniques.

Credits: 15 credits (7.5 ECTS credits).

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Since the discovery of HIV, great progress has been made in our understanding of the immune system. This module looks at topical aspects of this subject, with emphasis on the regulation of the immune response and dysfunctional immune systems in disease states.



Lectures:



Introduction to the immune systems of the body



Antigen processing and presentation:

Role of antigen presenting cells especially dendritic cells; processing and presentation of endogenous and exogenous antigens and virus evasion; immunotherapies



Transplantation immunology:

Basis of tolerance and graft rejection; clinical aspects of transplant rejection; general and specific immunosuppressive therapies



Autoimmunity:

The induction of tolerance to self; causes leading to autoimmunity; role of antibody; clinical examples of autoimmune disease



Hypersensitivity:

Type I (IgE-mediated); type II (antibody-mediated cytotoxic); type III (immune-complex mediated) and type IV hypersensitivity; clinical manifestations and therapies for hypersensitivity, the hygiene hypothesis, clinical examples of diseases



Role of cytokines in the immune system:

Properties of cytokines; cytokine receptors; cytokine-related diseases including inherited immunodeficiencies; the therapeutic applications of cytokines and their receptors



Cell migration and inflammation:

Lymphocyte recirculation; role of adhesion molecules; neutrophil and lymphocyte extravasation; the inflammatory process; chronic inflammatory diseases



Tumour immunology:

Tumour-specific and -associated antigens; immune response to tumours; tumour evasion of immune responses; cancer immunotherapy



Applied immunology - immunotherapy: vaccines; immunodiagnostics; immunoaffinity



Feedback session on Assessments 1 and 2 (Spring Term)

Revision session (Spring Term)

Credits: 15 credits (7.5 ECTS credits).

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This module focuses on the endocrine system, one of the two great control systems of the body. In conjunction with the nervous system, these two regulatory systems are responsible for monitoring changes in an animal's internal and external environments and directing the body to make any necessary adjustments to its activities so that it adapts itself to these environmental changes.



The emphasis will be on understanding the underlying principles of endocrinology, the mechanisms involved in regulating hormone levels within tight parameters in an integrated manner and the central importance of the hypothalamic-pituitary axis.



During the lectures each major endocrine gland or functional gland or functional group of glands will be explored in turn and specific clinical disorders will be used to illustrate the role of the endocrine organs in the maintenance of whole body homeostasis. The systems studied will include the following: thyroid gland, parathyroid gland and bone metabolism, adrenal gland, renal hormones (water and salt balance), pancreatic hormones, gut hormones and multiple endocrine neoplasia, gonadal function and infertility.



Consideration will be given to the methods available for the diagnosis of specific endocrine disease, including the measurement pf electrolyte and hormone levels, and the role of dynamic testing,



The role of the endocrine system in integrating metabolic pathways will be emphasised throughout the module and particular scenarios such as infertility, diabetes mellitus.

Credits: 15 credits (7.5 ECTS credits).

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This module will develop further understanding of the molecular basis of cancer, and will explore how this knowledge may be used to develop new therapeutic strategies to tackle the disease in its variety of forms. Topics to be covered include the regulation of gene expression, the role of growth factor signalling and oncogenes/tumour suppressor genes in disease progression; the cell cycle and apoptosis; cancer stem cells and differentiation; chemo-resistance and metastasis; DNA structure and stability; tumour immunology; targeted cancer therapies and clinical trial design.



Topics:

A. The Molecular Biology of Cancer: Regulation of gene expression; Growth factor signalling and oncogenes; Growth inhibition and tumour suppressor genes; the Cell Cycle and apoptosis.

B. Cancer stem cells and differentiation; chemo-resistance and metastasis.

C. Tumour immunology; targeted cancer therapies and clinical trial design.

D. DNA structure and stability: mutations versus repair.

Credits: 15 credits (7.5 ECTS credits).

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The module is divided into three roughly equal sized units, each dealing with a specific aspect of neurobiology. Throughout, both the normal system and diseases and disorders that arise as a consequence of abnormalities will be covered.



Unit 1: Development of the Nervous System



Looks at how the complex and intricately wired nervous system develops from a simple sheet of neuroepithelial cells by addressing the cellular and molecular basis of:

Neurulation (formation of the brain and spinal cord)

Nerve cell proliferation (Neurogenesis)

Differentiation and survival of nerve cells

Axon growth and guidance

Synapse formation (Synaptogenesis)



Unit 2: Signalling at the Synapse



Considers the molecules and mechanisms involved in transmission of signals between nerve cells:

Neurotransmitters and neuromodulators

Molecular mechanisms of transmitter release

Neurotransmitter receptors and transporters



Unit 3: The Brain and Behaviour



Explores how the nervous system controls a variety of behaviours including:

Learning and memory

Sleep and dreaming

Credits: 15 credits (7.5 ECTS credits).

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The module overviews the importance of studying ageing, the organisms and methods used to do so. It considers how organisms age, together with providing a detailed understanding of the processes and molecular mechanisms that govern ageing.



Introduction

Importance and principles of ageing research

Why do organisms age and theories of ageing: e.g. Damage theory, telomeres, genetics and trade off theories.

How ageing and lifespan is measured.

Overview of processes and pathways controlling ageing.



Methods in ageing research

Model Organisms: Benefits and problems associated with studying ageing in model organisms, including: yeast, worms, flies, mice, primates.

Systems approaches to studying ageing: e.g. high throughput DNA/RNA sequencing, high throughput proteomics and, metabolomics. Pros and cons of these methods, what we have learned from them?



Signalling pathways that control ageing

Insulin signalling pathway and Target of Rapamycin (ToR) pathway.

Organisation of pathways and the molecules involved, how they were discovered to be implicated in lifespan and ageing, ways of modelling and studying their molecular detail in animals e.g. genetic/ epistasis analysis.

The processes downstream of these pathways that allow them to control lifespan/ageing e.g. stress resistance, autophagy, reduced translation, enhanced immunity etc.

Cross-talk between pathways.

Dietary restriction, lifespan and ageing.

How dietary restriction works in different organisms, what signalling pathways and processes it affects.



Diseases of ageing

What these are e.g. Alzheimer's, Huntington's.

Overview of 'normal ageing' associated processes e.g. muscle weakening.

How they can be studied in model organisms and the importance of ageing research for treating these disorders.



Ethics of ageing research

Pros and cons of studying ageing with a goal of extending human lifespan e.g. insurance, health system, social, psychological implications.

Credits: 15 credits (7.5 ECTS credits).

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Building upon the second year course Microbial Physiology and Genetics 1, this advanced level course focuses on how physiological homeostasis is maintained in the bacterial cell in response to environmental stresses.



Lectures:

Introduction: Outline of how physiological homeostasis and adaptation is achieved in the bacterial cell.



Experimental approaches used to study microbial physiology and genetics: "Classical" and "reverse" genetics as applied to the study of bacteria. The use of reporter fusions. Transcriptomic and proteomic analysis of gene expression. Deep sequencing and metagenomics. Protein-nucleic acid interactions.



Transcriptional and post-transcriptional regulation of gene expression in bacteria: Transcription and translation in bacteria and the diverse mechanisms by which they are controlled. Phase variation and quorum sensing as modes of gene regulation.



Complex signalling and physiological control: Selected examples of physiological control in microorganisms, including the Sigma E envelope stress response pathway, regulation in response to nitrogen availability and nitric oxide stress, sensing, and detoxification mechanisms.



Microbial biodiversity at the physiological and biochemical level: Diversity of respiratory adaptations. Light harvesting: purple bacteria & cyanobacteria. Photosynthetic electron transport in purple bacteria & cyanobacteria.



Practical: Practical on E. coli demonstrating how the envelope stress response factor Sigma E and it's sRNA-controlled target regulate gene expression at the post-transcriptional level using lacZ reporter fusions.



Symposium: Group presentation of a research paper relating to topic areas in "Complex signalling and physiological control" or "Microbial biodiversity at the physiological and biochemical level"

Credits: 15 credits (7.5 ECTS credits).

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Cells and subcellular compartments are separated from the external milieu by lipid membranes with protein molecules inserted into the lipid layer. The structure and function of these two components are diverse, ranging from regulatory functions to maintaining the structure of the cell.



Topics:



Review of the fluid mosaic model for membrane organisation:

Experimental evidence for fluidity – lateral/rotational/flip-flop.



Membrane proteins:

Types: integral vs peripheral, and their experimental definition. Asymmetry and sidedness.

Bitopic and mono-topic, general review of synthetic mechanisms (signal sequences etc.) for bitopic protein synthesis.



Structures of channel and carrier proteins and some mechanisms and diseases.

Monotopic membrane proteins: exposed on one side of the membrane e.g. squalene-hopene cyclase, ras, fatty acylated proteins, GPI-linked (sticky fingers and greasy feet).

Peripheral membrane proteins. Interaction with the lipid bilayer via pleckstrin homology and other domains.

Generation of bitopic and monotopic proteins by differential exon usage in a single gene, e.g. NCAM.



Membrane lipids:

Types: phospholipids, sphingolipids and sterols; in vivo distributions.

Formation of bilayers: evidence for bilayer structures.

Sidedness and asymmetry of lipids: dynamics, and phases

Rafts and caveolae: structural evidence and relation to signalling.

Pointers to membrane lipid metabolism: phospholipases and signalling; metabolic defects and Tay-Sachs disease.



The in vivo structure of a mammalian plasma membrane:

The red cell membrane: observation of the requirements of such a membrane and how those requirements are not met in certain disease states (spherocytosis, elliptocytosis and pyropiokilocytosis). The putative CO2 metabolon. Structure of the red cell membrane and its associated cytoskeleton: the spectrin/ankyrin/actin system.



The membrane skeleton as a mechanism for restricting the mobility of membrane proteins in the plane of a membrane: relationship to non-erythroid cells, examples including cardiomyocyte membrane cytoskeleton and long QT syndrome resulting from ankyrin defects.



Practicals:

An exploration of the red cell membrane focusing on the anion transporter. The practical will include computer analysis of the sequence of the anion transporter to predict its structure in relation to experimental data from the practical.



Workshop: exam preparation.



Supervisions: problem solving based on past exam papers.

Credits: 15 credits (7.5 ECTS credits).

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This module begins by overviewing the principles of cell signalling and the diverse mechanisms used by cells to communicate, considering the main modes of cell-cell communication (adhesion and gap junctions; ligand-receptor complexes), the major classes of signalling molecules (hormones, neurotransmitters and growth factors) and the receptor types upon which they act. It then focuses on nuclear, G-protein coupled, and enzyme linked receptors covering in molecular detail these receptors and their associated signal transduction pathways.



Introduction :

Principles of cell signalling

Cell adhesion and cell communication (adhesion and gap junctions)

Signalling molecules: hormones, neurotransmitters, growth factors

Receptor types: Nuclear, G-protein coupled, Ion-channel linked, Enzyme-linked.



Nuclear receptors: cellular location and molecular organisation of receptors, structure-function-activity relationships, receptors as sequence-specific DNA binding proteins.

G protein coupled receptors: receptors coupled to heterotrimeric G-proteins, guanine binding proteins, effectors (e.g. adenylate cyclase, phospholipase C), second messengers (e.g. cAMP, IP3, DAG), protein kinases and phosphatases.

Receptor tyrosine kinases e.g. epidermal growth factor receptor (EGF) family and insulin receptor, and their varied roles in cellular metabolism, cell behaviour, development and disease.



Practical: Characterisation of G-protein coupled receptors using a cAMP-linked reporter gene assay.



Workshop: Overview of the module in preparation for revision/exam.

Credits: 15 credits (7.5 ECTS credits).

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This module surveys the full replication cycle of a broad range of viral families, including newly emerging infectious diseases. The module includes interactive discussions on a number of recent scientific publications that highlight the relevant and important issues in the field of virology today.



Part A: survey of viral families and their properties

Virus families and taxonomy

Viral structure

Viral genomics

Virus replication (overview)

Virus transmission

Viral diseases and host interactions

Anti-viral therapeutics and vaccination



Part B: detailed examination of the different mechanisms of viral replication

Entry

Protein synthesis

Genome replication

Assembly

Budding

Transmission



Part C: fundamental methods in virus research

Key historical methods

Current standard techniques

Novel methods



Part D: virology research design

Grant writing

Oral presentation

Research review and evaluation

Credits: 15 credits (7.5 ECTS credits).

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The past decade has seen significant advances in our ability to obtain biological data, be it protein structures or genome sequences. The bioinformatics element of this module will focus on modelling the structure, interactions and function of proteins. The genomics element will introduce the basic concepts of genome sequencing and what we have learnt from the sequencing of over 1000 different organisms. Finally the module will combine both elements to use protein modelling to identify how genetic variants (e.g. mutations) lead to disease. The lectures will teach the theory and the computer workshops will introduce some of the many web servers available to perform bioinformatics analyses.



Topics:



A. Bioinformatics Data sources & Sequence analysis:

Databases and data availability. Using sequence data for analysis – sequence searching methods, multiple sequence alignments, residue conservation, Phylogenetics, Protein domains and families (e.g. Pfam, Interpro).



B. Protein Bioinformatics Methods

Protein structure and function prediction. Prediction of binding sites/interfaces with small ligands and with other proteins. Bioinformatics analyses using protein data.



C. Genomics

An introduction to DNA analysis methods moving onto omics approaches, primarily focussing on the data available from DNA sequencing – how it can be used to compare genomes (comparative and functional genomics). Metagenomics and transcriptomics will also be covered.

Credits: 15 credits (7.5 ECTS credits).

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BI639 Frontiers in Oncology

This module introduces the basic principles of cancer biology and cancer therapy. It will explain the characteristics of cancer and why the development of more effective anti-cancer therapies is so extremely challenging. The module includes interactive discussions on a number of recent scientific publications that highlight the relevant and important issues at the frontiers of cancer research today.



Part A: survey of the leading issues in oncology

origin of cancer

cancer biology

cancer therapies



Part B: fundamental methods applied in oncological research

Key historical methods

Current standard techniques

Novel methods



Part C: oncology research design

Grant writing

Oral presentation

Research review and evaluation

Credits: 15 credits (7.5 ECTS credits).

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The curriculum is based on the Small Firms Enterprise Development Initiative (National Standards-setting body for small business) Standards for Business Start-up, but has been expanded to include contemporary issues such as Intellectual Property and recent legislation. It will include the following areas of study:

• Why firms become insolvent – economic financial and operational reasons for business failure, risks & liabilities, skills requirements for business ownership, self-development planning, sources of advice and support for businesses

• The new business planning process and format, developing & evaluating the business idea, producing a business plan for potential lenders.

• Financial aspects – budgetary planning & control, cash-flow and working capital, understanding financial accounting and key financial documents, break-even analysis, credit control and debt recovery, understanding PAYE & VAT.

• Market research, competition and barriers to market entry, identifying customers, market segmentation, planning the sales & marketing processes, customer perceptions & customer care, developing quality standards for the business

• Legal issues: reporting requirements, UK & EU law relevant to small businesses, business formats & trading status and their respective risks and liabilities, insurance, insolvency; patents, copyrights and IPR.

• Planning & employing staff, planning and obtaining premises, physical & financial resources; phased implementation of the business plan.

Credits: 15 credits (7.5 ECTS credits).

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