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 nucleotides) will be contrasted with the enormous variety and adaptability that is obtained with the different macromolecules (proteins, carbohydrates, lipids and nucleic acids). The molecular structure of macromolecules will be highlighted and linked with function of the macromolecules in living cells and organisms. Physical methods for purifying, characterising and further investigating macromolecules will be described including spectroscopy, chromatography and electrophoresis. The module will be delivered by lectures, laboratory sessions and a model-building workshop. Feedback will be given on the formative lab-based sessions to ensure students understand what is expected in the assessed practical. Short tests (formative only, on Moodle) will be used during the module to help students test their own knowledge and one summative (assessed) MCQ will monitor that the right material has been extracted from taught sessions.

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.

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 specialized cell types and complex multi-cellular organisms. The principles of 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 multi-choice testing and feedback.

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 (whole day)

This module will consider 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 cardiovascular system

The respiratory system

The immune system and inflammation

Blood cells and clotting

The digestive system, liver and pancreas

The Urinary system

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 Kent - 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

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.

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.

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 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.

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

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.

Lectures:

Introduction: The ecological, medical, scientific and commercial importance of bacteria. Bacterial evolution and taxonomy.

Microbial biodiversity at the structural level: Composition of the average bacterial cell and basic bacterial cell structure. Gram positive and gram negative. Archea. Organisation of DNA. Membranes and the transport of small molecules into and out of the cell. Peptidoglycan and LPS and their importance in pathogenesis. The location and function of proteins. Capsule, flagella and adhesins.

Introduction to growth, fuelling and biosynthesis: Division by binary fission, including growth equations. Growth in batch and chemostat cultures; liquid vs. solid media. Nutritional and non-nutritional factors affecting growth (temperature, osmolarity, pH and antibiotics). Physiological state and balanced growth. Adaptation to extreme conditions.

Microbial biodiversity at the physiological and biochemical level: The diversity in bacterial metabolism (nutrient sources (particularly carbon and nitrogen)), photosynthesis, aerobic and anaerobic growth and alternative terminal electron acceptors. Fermentation. The inverse relationship between growth factor requirements and biochemical complexity. The ecological significance of bacteria.

Synthesis, localisation and assembly of macromolecular structures: DNA replication and transcription. Translational and protein localisation, assembly of flagella and adhesins. Membranes, including LPS. Peptidoglycan. Antibiotics that inhibit peptidoglycan biosynthesis. Capsules.

Microbial communities and ecology: growth and survival in the real world (e.g. soils and sediments), studying populations and individuals. Biofilms and complex communities. Diauxie and growth.

Signalling and physiological control: Introduction to bacterial genetics. The regulation of gene expression at the transcriptional and post-transcriptional level in response to environmental factors Chemotaxis.

Practical: "Antibiotics" in which students follow the growth of bacteria upon treatment with bacteriostatic and bactericidal antibiotics and answer questions about data concerning the mode of action of antibiotic resistance presented in the laboratory manual.

Workshop: "Growth and viable counts" in which the students are given numerical data + growth equations and have to define factors such as (i) dilutions needed to give specific cell numbers, (ii) generations of growth to achieve specific cells numbers (iii) growth rate/doubling time. Designed to give students the skills required to manipulate bacterial cells to achieve correct cell density and growth phase for practical work.

Medically important microbial diseases

Gastrointestinal infections, Upper respiratory tract infections, Genital infections

Lower respiratory tract infections, CNS infections, Infections of the skin, Urinary tract infections, Ear and eye infections, Parasitic infections, Mycoses

Immunological Topics

Introduction to the basic concepts of innate and adaptive immunity to pathogens. Immune defence mechanisms against bacterial, viral and parasitic infections. Antibody classes, antigen processing, complement, cytotoxic cells, interferons, the generation of antibody diversity. Cell communication, and the regulation of immunity by T cell . Immunopathology, including autoimmunity, allergy and transplant rejection.

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.

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:

Drug receptor binding data analysis

Electron transport and oxidative phosphorylation in mitochondria. The chemiosmotic hypothesis, mechanism of ATP synthase, ATP yield, disorders associated with mutations in the mitochondrial genome.

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; Mitochondrial inheritance.

Metabolism of amino acids and nucleotides: Amino acid metabolism involved in the production of neurotransmitters, role of amino acids in phenylketonuria, purine/pyrimidine degradation, and the onset/treatment of Gout.

The urea cycle: The link between nitrogen and carbon metabolism, and diseases associated with enzyme deficiencies. Treatments for defects in urea cycle enzymes.

Cholesterol metabolism: Biosynthesis and transport of cholesterol, regulation of cholesterol synthesis, hypercholesterolemia/atherosclerosis, and the use of statins to control cholesterol levels.

Vitamins and malnutrition: Vitamin requirements with a metabolic focus of the roles of vitamin A in the visual cycle, vitamin C in connective tissue, vitamin D in bone formation, and vitamin K in blood clotting

Sugar metabolism: Glucose transporters and disease; Glycogen storage diseases; 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.

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.

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.

The cell is the fundamental structural unit in living organisms. Eukaryotic cells are compartmentalized structures that like prokaryotic cells, must perform several vital functions such as energy production, cell division and DNA replication and also must respond to extracellular environmental cues. In multicellular organisms, certain cells have developed modified structures, allowing them to fulfil highly specialised roles. This module reviews the experimental approaches that have been taken to investigate the biology of the cell and highlights the similarities and differences between cells of complex multicellular organisms and microbial cells. Initially the functions of the cytoskeleton and certain cellular compartments, particularly the nucleus, are considered. Later in the unit, the mechanisms by which newly synthesised proteins are secreted or shuttled to their appropriate cellular compartments are examined.

Lectures:

Cell motility and the cytoskeleton. - types of cell movements. Actin-based mechanisms - actin/myosin systems in muscle and other cells in higher eukaryotes and the discovery of corresponding microbial systems. - microtubules and their role in intracellular transport: dynein and kinesin. Microtubules in cilia and flagella. ATP and GTP driven processes - the family of intermediate-sized filaments; their structure, cellular role. Concepts of the evolution of intermediate filaments between microbes and man.

Regulation of the mitotic cell cycle and the dynamic structure of the nucleus. – the

interphase nucleus - chromatin structure (histones, nucleosomes, higher order folding;

telomeres; kinetochore etc), nucleolus, nuclear envelope structure, biogenesis of ribosomes,

genetic approaches to analysis of regulation of mitosis, definition of yeast cdc genes;

comparison with biochemical approaches, regulation of progression from G1 ? S ? G2 ? M.

Cycle exit to G0 and return. Growth factor, signalling and apoptosis. Chromatin structure and

its regulation through the cycle, Dynamics of the nuclear envelope and chromosome/chromatid

separation.

Overview of membrane traffic in eukaryotic cells. - relationship of endocytotic and

exocytotic pathways, compartments and sorting.

Biogenesis of proteins destined for organelles or for secretion.- experimental approaches –

yeast and bacterial sec genes vs biochemical dissection of mammalian secretory tissue, signal

sequences targeting proteins to different organelles, folding and post-translational modification

of proteins in the secretory pathway, eukaryotic and prokaryotic secretory pathway –

biochemical and genetic dissection of compartments, transport mechanisms and targeting.

Practicals:

Actomyosin contraction in myofibrils using phase microscopy .

Supervisions:

Reading and précis of a scientific paper in cell and molecular biology. Presentation of its chief findings and impact

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.

Since the discovery of HIV, astonishing progress has been made in our understanding of how the immune system functions. The aim of this Advanced Immunology module is to review topical aspects of this fascinating subject, placing emphasis on the regulation of the immune response, and the role of dysfunctional immune systems in the aetiology of a variety of disease states. Students will be expected to devote time to private study, consulting course texts, reviews and primary literature.

Topics to include –

Antigen processing and presentation - Role of antigen presenting cells; dendritic cells;

processing and presentation of endogenous and exogenous antigens

Transplantation immunology - Basis of tolerance and graft rejection; clinical applications of transplantation; general and specific immunosuppressive therapy

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

Autoimmune disease - Organ-specific autoimmune diseases; systemic autoimmune diseases; induction of autoimmunity; treatment of autoimmune disease

Role of cytokines in the immune system - Properties of cytokines; cytokine receptors; cytokine-related diseases, including inherited immunodeficiencies; 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 - appears throughout the lecture series

Autophagy and the Microbiome

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.

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.

Bacterial pathogens:

1. Microbial pathogenicity: variations on a common theme.

2. Methodology of studying bacterial pathogenesis.

3. Virulence factors including toxins and adhesins.

4. Mechanisms of Pathogenesis.

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

Viral pathogens:

1. 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.

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

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

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

Human fungal pathogens:

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

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

3. Whole genome analysis of fungal pathogens

4. 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):

1. Parasites and pathogenicity, transmission and diversity.

2. Definitions on parasitic lifestyle.

3. Investigations on worldwide parasitic outbreaks (e.g. malaria, trypanosomiasis, cryptosporidiosis)

and their socio-economical effects.

Early in the Autumn term, projects are assigned to students by the project co-ordinator (a member of academic staff), where possible in accordance with student choice. Students then meet with their project supervisor to discuss the objectives of the project and obtain guidance on background reading. During the Autumn term students write a brief formative literature review on the project topic providing them with a good background before embarking on the project work.

The main project activities take place in the Spring term. Students taking laboratory projects spend 192 hours (24 hours per week for 8 weeks) in the lab planning, carrying out and documenting experiments. A further 108 hours are allowed for background reading and report writing. There are informal opportunities to discuss the project work and relevant literature with the supervisor and other laboratory staff. Formal meetings may be arranged at the discretion of the student and supervisor. Students undertaking non-laboratory projects are based in the library or, occasionally, in the laboratory; they are expected to dedicate 300 hours to their project work. Non-laboratory students are strongly encouraged to meet with the supervisor at least once a week to discuss progress and ideas and to resolve problems. At the end of the formal project time, students are allowed time to complete the final project report, although they are encouraged to start writing as early as possible during the Spring term. The supervisor provides feedback on content and style of a draft of the report. In addition, students are expected to deliver their findings in presentation lasting 10 minutes with 5 minutes of questions.

Organisation and Content:

Projects are designed by individual members of staff in keeping with their research interests and fall into one of four categories:

• Wet/Dry Laboratory and Computing: practical research undertaken in the teaching laboratories, or on computers followed by preparation of a written report

• Dissertation: library-based research leading to production of a report in the style of a scientific review

• Business: development of a biotechnology business plan

• Communication: similar to dissertation projects but with an emphasis on presenting the scientific topic to a general, non-scientist audience

The module begins by overviewing the diverse mechanisms used by cells to communicate, considering the main modes of cell-cell communication, the major classes of signalling molecules 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 guanine nucleotide binding proteins (G proteins). Composition and classification of G-proteins, their activation and modulation by toxins and disease.

Second Messengers and Protein Phosphorylation (kinases and phosphatases).

Cyclic Nucleotide-Dependent Systems: G proteins in regulation of adenylyl cyclase-cAMP-protein kinase A (PKA) and guanylyl cyclase-cGMP pathways. Physiological roles e.g. in visual transduction and glycogen metabolism.

Inositol lipids in signal transduction: Regulation of phospholipase C. Inositol polyphosphates (e.g. IP3) and diacylglycerol (DAG) in regulation of Ca++-dependent kinases. Roles in specific cellular responses e.g. regulation of protein kinase C.

Interactions of Signalling Pathways:

'Cross-Talk' between different pathways and messenger molecules.

Enzyme Linked Receptors:

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

Molecular organisation of receptors, autophosphorylation of intracellular domains

Intracellular signalling pathways: activation of monomeric G-protein Ras, leading to activation of the mitogen activated protein (MAP) kinase cascade.

Integration of signalling components: Role of adapter proteins (e.g. GRB2) and their protein-protein interaction domains (SH2, SH3 etc.) in linking ligand-receptor complexes to intracellular proteins.

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

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

Cells and subcellular compartments are separated from the external milieu by lipid membranes with protein molecules inserted into the lipid layer. The aim of this module is to develop understanding of both the lipid and protein components of membranes as dynamic structures whose functions are integrated in cellular processes.

Lectures:

1. Review of the fluid mosaic model for membrane organisation

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

2. Membrane proteins

a. Types: integral vs peripheral, and their experimental definition. Asymmetry and sidedness. Overview of types of transmembrane proteins, and lessons on prevalence and functions from genome analysis

b. Transmembrane protein function exemplified through transporters. Structures of channel proteins and carrier proteins, their mechanisms and disease links

c. Monotopic membrane proteins: exposed on one side of the membrane examples and structures

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

e. Peripheral membrane proteins. Domains that allowInteraction with the lipid bilayer

2. Membrane lipids

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

b. Formation of bilayers: evidence for bilayer structures.

c. Sidedness and asymmetry of lipids: dynamics and phases.

d. Pointers to membrane lipid metabolism: phospholipases and signalling; metabolic defects and disease.

3. The in vivo structure of a mammalian plasma membrane

a. 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.

b. The membrane skeleton as a mechanism for restricting the mobility of membrane proteins in the plane of a membrane: evolutionary considerations and disease states in other cell types e.g. ankyrin-linked dysfunction of cardiac ion transport in heart diseases.

Practical

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. An additional aspect of this practical will be recapitulation of the use of some techniques widely used in final year projects (SDS gel and blotting).

Workshop: exam preparation

Supervisions: Problem solving based on past exam papers.

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

Lectures

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

2. 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.

3. 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.

4. 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.

5. 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"

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.

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

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.

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

DNA structure and stability: mutations versus repair.

Tumour immunology; targeted cancer therapies and clinical trial design.

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:

1. Neurulation (formation of the brain and spinal cord)

2. Nerve cell proliferation (Neurogenesis)

3. Differentiation and survival of nerve cells

4. Axon growth and guidance

5. Synapse formation (Synaptogenesis)

Unit 2: Signalling at the Synapse

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

1. Neurotransmitters and neuromodulators

2. Molecular mechanisms of transmitter release

3. Neurotransmitter receptors and transporters

Unit 3: The Brain and Behaviour

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

1. Learning and memory

2. Sleep and dreaming

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

1. Importance and principles of ageing research

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

3. How ageing and lifespan is measured.

4. Overview of processes and pathways controlling ageing.

Methods in ageing research

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

2. 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

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

2. 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.

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

4. Cross-talk between pathways.

5. Dietary restriction, lifespan and ageing.

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

Diseases of ageing

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

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

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

Ethics of ageing research

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

This module focuses on the endocrine system, which in conjunction with the nervous system, is 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 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 diseases, including the measurement of 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

This module is designed to provide students across the university with access to knowledge, skill development and training in the field of entrepreneurship with a special emphasis on developing a business plan in order to exploit identified opportunities. Hence, the module will be of value for students who aspire to establishing their own business and/or introducing innovation through new product, service, process, project or business development in an established organisation. The module complements students' final year projects in Computing, Law, Biosciences, Electronics, Multimedia, and Drama etc.

The curriculum is based on the business model canvas and lean start up principles (Osterwalder and Pigneur 2010) on designing a business plan for starting a new venture or introducing innovation in an established organisation. It includes the following areas of study:

• The new business planning process and format, developing and evaluating the business idea, producing a business plan, which includes four main sections, namely, business concept, marketing plan, operational plan and financial plan.

• Researching internal and external environment – market research, value co-creation with customers, company’s macro (i.e. PESTEL) and industry (Porter’s five forces) environment analysis, internal company analysis (Resource Based View), external collaborator analysis, and SWOT

• Developing the business concept – Identifying/developing the value proposition, specifying the business offer (i.e. use product anatomy analysis for presentation), deciding an appropriate ownership structure, laying out mission, aims and objectives (i.e. using SMART), and identifying legal formalities including intellectual property strategies.

• Developing the marketing plan – Identifying target customer groups, designing customer relationship management strategies and distribution channels, planning the sales and marketing processes, customer perceptions and customer care, developing quality standards for the business (i.e. using 7 Ps analysis for presentation).

• Developing the operation plan – Identifying key activities to be carried out, matching key activities with resources for an effective and efficient use of resources, planning and employing staff, planning and obtaining premises, physical and financial resources; phased implementation of the business plan.

• Developing the financial plan – Identifying appropriate sources of finance, and evaluating and managing the financial viability of a business by developing Forecast cash flow statement, Sales and Profit account and Profit and Loss Account, a description of the composition of the balance sheet, financial indicator- Breakeven analysis, by highlighting underlying assumptions.