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Part 1b List of Lecture synopses

Synopses Of Lectures - MVST Part IB Pathology (Biology of Disease) and NST Part IB Pathology

Michaelmas 2015

Introduction to pathology, disease and immunity:  Professor J Kaufman

Pathology is the study of disease, which now is carried out by a wide range of approaches. Cell injury is the starting point for most disease processes, caused by unfortunate genetics, infection by pathogens, cancers, toxic substances and forces, nutrition and ageing. Cell death occurs if damage is beyond repair, generally through apoptosis or necrosis. The immune response can protect the host from pathogens and cancers, but can also over-react causing damage. This immune response arises from very complex system that can be divided into innate and adaptive immunity. Immune mechanisms are present in nearly all cells, but there are dedicated immune tissues and cells that are crucial for the immune response. Many (but not all) cells of the immune system are hematopoietic, and can be identified by morphology, staining with chemical dyes, and binding monoclonal antibodies (mAb). These mAb recognise cell surface molecules, many of which have been given CD numbers.


Innate Immunity: Professor J Kaufman

The innate immune system is crucial to preventing most infections as well as being required to begin an adaptive immune response. There are three modes of recognition that initiate an innate response. Pathogen-associated molecular patterns (PAMPs) refer to molecules that are common and essential for a category of pathogen, and are different from the host. Cell surface, endosomal and cytoplasmic molecules called pattern recognition receptors (PRRs) recognise these patterns. The innate immune system also recognises danger-associated molecular patterns, which are signs of cellular stress, often molecules that appear in uncharacteristic locations, as well as noxious extracellular molecules. Finally, the lack of particular self-molecules (missing self) can be recognised by several systems of innate immunity, including natural killer (NK) cells.


Inflammation:  Professor J Kaufman

If pathogens penetrate the barriers (such as epithelial cells), inflammation is induced in the site of infection. This is a coordinated response to infection or injury that results in a battery of effector mechanisms to eliminate the infection. Endothelial cell damage initiates enzyme cascades, including kinin, clotting, fibrinolysis and complement. Tissue resident macrophages and mast cells also contribute cytokines and chemokines. Increased vascular permeability allows fluid, proteins and inflammatory cells such as neutrophils and monocyte/macrophpages to reach infected tissues. Local acute inflammation generally resolves as the tissue heals, but failure to resolve can result in chronic acute inflammation. Persistence of an intracellular pathogen can result in a granuloma, in which the infected tissue is contained. Systemic infection can provoke septic shock and death.


Complement: Professor J Kaufman

Complement is a very ancient system that includes some 30 soluble blood proteins, involved in activation of inflammation, opsonisation of microbes and lysis of target cells. Many of these proteins are part of enzyme cascades, which lead to explosive responses that must be carefully controlled. There are three main pathways that all converge on complement component C3, the key molecule in the system. Host cells are protected by a variety of regulatory proteins, including decay accelerating factor (DAF) and membrane co-factor protein. The alternative cascade can be initiated by pathogen surfaces, and is the first system to be activated. The lectin cascade recognises carbohydrates and is the second system to be activated. The classical cascade is initiated by C-reactive protein from the inflammatory pathway, or by antibodies from the adaptive immune response. Among the consequences of complement activation are the generation of chemotactic protein fragments (anaphylotoxins), covalent attachment of molecules to facilitate phagocytosis (opsonisation), and formation of the membrane attack complex to kill cells.


The Adaptive Immune System:  Dr A P Kelly

The theoretical basis for an adaptive immune system requires the possession of a large repertoire of clonally variable receptors.  This requirement is met by lymphocytes.  The acquisition of clonally variable receptors underpins the characteristics of the adaptive immune response, which distinguish it from innate immunity, namely specificity and memory.  In fact the vertebrate immune system has developed two complementary but distinct antigen-specific receptor repertoires, expressed by the B and T lymphocytes respectively.  The essential characteristics of each will be emphasised – native recognition by B cells, processed antigen by T cells.  The organisation of lymphoid tissue will be discussed and the recirculation properties of lymphocytes – encapsulated by the phrase “patrol and respond” – will be introduced.


B Cells and Antibodies:  Dr A P Kelly

The protein structure of antibody molecules will be covered from four aspects; the division of the molecules into antigen binding (variable) and effector function-linking (constant) regions; the formulation of the antigen-combining site by the folding of polypeptide chains – the heavy and light chains; the mobility within the protein and its significance in the formation of antibody-antigen complexes; the existence of membrane bound and soluble forms of protein.  The different classes and subclasses of antibody will be introduced with a brief review of their properties.  The principle of somatic diversity of immunoglobulin molecules will be stressed.  The functions of antibody and their role in recruiting immune effector mechanisms via Fc receptors and complement will be discussed.  The concepts of avidity and affinity will be defined.


The Major Histocompatibility Complex:  Dr A P Kelly

The protein structure of MHC molecules will be described and the properties of MHC molecules in binding peptides illustrated.  The nomenclature of MHC molecules will be explained, including the existence of distinct classes and the co-dominant nature of expression.  The genetic polymorphism of MHC molecules will be discussed in outline and the functional consequences of this explained in terms of peptide binding.  The cell biology of class I and class II molecules and their roles in presenting antigen from different sources will be discussed.


T Cells:  Dr A P Kelly

An outline of the development of T cells with emphasis on the outcome in terms of repertoire selection, tolerance and the generation of distinct classes of T cells which recognise the distinct classes of MHC (CD4 and CD8 T cells).  The differentiation of function between CD4 and CD8 T cells will be presented in simplified form.  T cell receptor will be introduced and the mechanism of repertoire generation examined.  The role of T cells in regulating antibody responses and the cellular interactions of dendritic cells, T cells and B cells will be discussed.  The concepts of co-stimulation, class switching and affinity maturation will be explained. 


Tolerance:  Professor J Trowsdale

A range of processes is in place to avoid recognition and damage of self tissues, a concept referred to as tolerance. Mechanisms of tolerance are generally divided into central and peripheral.  Central tolerance of T cells takes place in the thymus and in the bone marrow for B cells.  Mechanisms for peripheral tolerance have been characterised as anergy, ignorance and suppression.  Recently the profound role of regulatory T cells has become to be appreciated. The self, non-self models of Medawar and Burnet will be compared to Matzinger’s “Danger Hypothesis”.  The experimental manipulation of tolerance will be discussed, with one or two examples.


Autoimmunity:  Professor J Trowsdale

Although the immune system has an elaborate system of checks and balances to ensure self tolerance, occasionally this system breaks down. When the immune system attacks host components causing pathological change, this is called autoimmunity. Many people experience an autoimmune reaction during their lifetime. Mostly these are short-lived, self-resolving sequelae of infection. However in some 5% of individuals the reaction is chronic, debilitating and even life-threatening. It is these latter conditions where serious immunopathology occurs, usually considered as autoimmune disease. Autoimmunity results from the breakdown of self-tolerance.  Autoimmune disease should be seen as a spectrum encompassing single-antigen organ-specific conditions at one extreme to systemic polyspecific diseases at the other.  The profound influences of genetics and environmental factors will be explored.  Clinical examples will be used to illustrate the underlying causes of autoimmunity.  Different explanations for the initiation of autoimmune disease will be compared.  The role of experimental models of autoimmune disease in elucidating the underlying causes and mechanisms will be discussed.


Hypersensitivity:  Professor J Trowsdale

Hypersensitivity refers to immune responses that are damaging rather than helpful to the host. In other words these are over-reactions of the immune system. Gell and Coombs proposed a classification scheme that defined four types of hypersensitivity reactions. The first 3 are mediated by antibody, the 4th by T cells. The four types of hypersensitivity will be outlined. Type 1 hypersensitivity will be familiar to the majority of students as allergy.  The role of IgE and mast cells will be briefly outlined.  This will be compared to type II hypersensitivity, which involves IgM or IgG. Blood transfusion is the oldest form of transplantation and is an example of type II hypersensitivity. Both ABO and Rhesus blood group systems will be covered. Type III IgG hypersensitivity reactions occur when the antigen is soluble and in high quantities, in contrast to low levels which tend to produce IgE responses. Immune complexes form and are deposited in tissues. Finally, type IV or Delayed type hypersensitivity (DTH) is mediated by specific T cells, that release cytokines, which in turn recruit mononuclear cells. The effect is usually maximal in 48-72 hours.


Transplantation:  Professor J Trowsdale

Transplantation is the introduction of biological material - organs, tissue, cells, fluids - into an organism. The problem with transplanting tissue is that most cells express polymorphic surface antigens encoded by the MHC. Variation between the donor and recipient at the MHC results in rejection. Even if there is a perfect match other ‘minor’ antigens can be recognised by the immune system. Unlike ABO blood typing there are no universal donors. If tissue is mis-matched it is generally rejected.  This topic illustrates self non-self discrimination and the importance of inflammation as a trigger of immune responses.  Discrimination of the two pathways, direct and indirect, of cellular transplant rejection, provides reinforcement of the concepts of antigen presentation. Different transplant situations will be discussed in relation to the need for donor/recipient matching and immunosuppression.

The nature of viruses:  Professor G L Smith

Viruses are submicroscopic, intracellular parasites. At their simplest they consist of a nucleic acid genome surrounded by a protective shell composed of repeating protein subunits, but some viruses acquire an outer membrane as they leave the cell and are therefore chemically more complex. The great diversity of viruses results from the different symmetrical arrangements of the protein subunits in the shell, the different types of nucleic acid that comprise the genome and the wide range of coding potential of the genome. These features are used to describe and classify viruses. Despite the great variation in the virus size and structure, the life style of viruses is fundamentally similar. A virus must attach to the surface of a host cell via specific receptors and penetrate the cell to deliver its genome into the cell. The virus genes are then expressed to produce new virus proteins that replicate the genome and provide subunits for new virus particles. Association of new protein shells with progeny genomes completes the cycle. The purpose of the lecture is to describe the nature of viruses and to illustrate common features of their replication cycle.


Consequences of viral infection:  Professor G L Smith

This lecture will start by illustrating how viruses with RNA or DNA genomes convert their genes into mRNA to produce new proteins and how these diverse genomes are replicated. Once inside the cell the virus is, in essence, a set of parasitic genes whose purpose is to subvert the cell’s synthetic machinery and convert the cell to a virus production factory. We will consider how this subversion is achieved, how the cell responds and what changes virus infection can bring to cells. DNA viruses require high levels of deoxyribonucleotides for genome replication and may induce the resting cell into cell cycle to produce these dNTP pool sizes. Although virus replication is one consequence of infection, this is not the only outcome and others include latent infection and cell transformation leading to cancer. The consequences of infection thus range from proliferation to cell death.


Viruses in the multicellular host:  Professor G L Smith

In the multicellular host the virus is confronted with physical and immunological defences to infection. To replicate and spread to other hosts a virus must gain access to susceptible cells and tissues (a portal of entry), multiply to high levels (at an amplification site), and leave the infected host by a portal of exit that ensures transmission to new hosts. The cell senses virus infection via pattern recognition receptors (PRRs) that recognise pathogen associated molecular patterns (PAMPs) and responds to infection by producing interferons, cytokines and chemokines and by undergoing apoptosis. Interferon is a cytokine that indirectly inhibits protein synthesis in infected cells, and so prevents virus replication. The importance of different components of the defence system varies depending on the virus. Viruses have many strategies to evade or inhibit the host innate response to infection and an understanding of the important responses to a particular infection, and of the evasion strategies of the virus concerned, are important in vaccine or immune therapy design.


How viruses persist and are transmitted.  Professor G L Smith

Most viruses are eliminated by host responses. These viruses cause acute infections and are under constant pressure to find new hosts if they are to survive. Some viruses are not eliminated, but persist in the host as chronic infections or latent (silent) infections that reactivate from time to time. Superficial infections use the same tissue for entry, amplification and exit, whereas systemic spread results in the infection of a wider range of tissues, more complex pathological outcomes, and a variety of possible exit routes. This lecture will examine the different strategies of viruses that cause acute or persistent infections and the implications of these strategies for transmission and survival of the virus in host populations. The pathological consequences of infection depend on interactions between the virus and the host. Acute infections often cause direct tissue damage and acute inflammation. Persistent viruses survive in the host in the face of an immune response that controls the virus, but fails to clear it. In the long term, chronic immunopathological damage may result.


Influenza and hepatitis viruses:  Professor G L Smith

Influenza virus causes repeated, acute respiratory infections that are highly seasonal. This virus is able to escape existing immunity by undergoing antigenic variation of its surface protein the haemagglutinin (HA) by either antigenic drift or shift. Drift is the gradual accumulation of mutations that enable escape from neutralising antibodies, whereas shift is a complete change of the HA protein caused by re-assortment of RNA segments during a co-infection with two influenza viruses. This can lead to emergence of an influenza pandemic. Hepatitis B virus is a hepadnavirus and has a small, circular, DNA genome of only 3.2 kbp. Despite being a DNA virus, HBV replicates via reverse transcription like the retroviruses. HBV infection can cause either an acute jaundice or chronic infection that predisposes to subsequent development of liver cancer. An effective vaccine HBV has been used widely since 1986. Hepatitis C virus (HCV), in contrast, is an RNA virus and shows tremendous genetic diversity. Like HBV, HCV can cause either acute or chronic infection and the latter predisposes to liver cancer. Unlike HBV, there is no vaccine to prevent HCV infection, however, several anti-HCV drugs have been developed that cure infection in most cases.


AIDS, Ebola and prions: Professor G L Smith

The lecture will consider human immunodeficiency virus (HIV), the cause of AIDS, the recent Ebola virus epidemic in Africa and prion diseases. HIV is a retrovirus that infects helper T lymphocytes that express the CD4 protein. The destruction of these cells that are needed for a functional immune system leads to an acquired immune deficiency syndrome (AIDS) in which it is opportunistic infections, rather than HIV itself, that kills the patient. AIDS is a sexually transmitted disease for which there is no vaccine and no cure. Although many anti-HIV drugs have been developed, these do not clear the virus and if they are withdrawn the virus returns. Ebola virus is a filovirus, a filamentous RNA virus that causes an acute haemorrhagic disease in man. During the last 18 months an epidemic in West Africa has killed more than 11,000 people. It has been brought under control by public health measures and candidate vaccines are showing promise in early trials. Prions are infectious proteins and cause diseases in man and animals called transmissible spongiform encephalopathies (TSEs). These diseases include kuru in Papua New Guinea, Creutzsfeldt-Jakob disease (CJD), scrapie in sheep and bovine spongiform encephalopathy (BSE) in cattle. The BSE epidemic in UK led, a decade later, to increased numbers of cases of CJD called variant CJD in humans, presumably due to ingestion of BSE-infected food.


Preventing and treating virus infection:  Professor G L Smith

This lecture will consider how virus infections may be prevented by i) public health measures such good hygiene, clean water, surveillance and quarantine, ii) vaccines and iii) anti-viral drugs. Most of the lecture will be devoted to vaccination that remains the most effective method of controlling virus infections and this will be illustrated by the eradication of smallpox. The lessons learned from this success that are applicable to the control of other virus infections will be discussed. The milestones in the development of the virus vaccines available today, the properties of live, dead and passive virus vaccines, and the impact of immunological and molecular knowledge on vaccine design will be considered. The lecture will also consider anti-virus drugs and how these can be specific for the virus without being toxic to the host cell.

Characteristics of Fungi: Dr A Carmichael

The characteristics of fungi in general. Host defences against fungi. Anti-fungal drugs. The patterns of fungal infections, including commensals, superficial infections and systemic (deep) infections.

Systemic fungal infections: Dr A Carmichael

The distinctions between systemic pathogens and systemic opportunists, with examples of the spectrum of serious fungal infections including environmental dimorphic fungi, Candida albicans, Pneumocystis and Aspergillus.

Lent 2016

Bacterial disease – Past, Present and Re-emerging: Professor C Hughes

The spectrum and nature of bacterial infection and disease. Bacterial transmission. Sites of infection.

Bacteria: Prokaryotic Pathogens: Professor C Hughes

Prokaryotic cell structure and function. Growth and adaptability. Genetics.

Bacteria – Host Interaction: Pathogenicity: Professor C Hughes

Host defences against bacteria. Bacterial mechanisms for colonisation, survival and transmission. Pathogenicity is multifactorial and tightly regulated.

Host Damage – Toxins, the Host Response: Professor C Hughes

Protein Toxins. Inflammation, immunopathology.

Bacterial Pathogenicity in the Respiratory Tract: Professor C Hughes

Examples of bacteria that colonise the respiratory tract.

Bacterial Pathogenicity in the Gastrointestinal Tract: Professor C Hughes

Examples of bacteria that colonise the gastro-intestinal tract.

Combating Bacterial Disease: Professor C Hughes

Public health, antibiotics, vaccines. The nature and threat of drug resistance.

Introduction to Parasitic Diseases: Professor D Dunne

An introduction to the scope of Parasitology as a disciple, the range of protozoan and metazoan eukaryote organisms that cause important human and veterinary infections, and the global importance of these diseases that they cause.

Key Examples of Parasitic Diseases: Malaria: Professor D Dunne

In this and the following lecture, two major parasitic diseases, one caused by protozoan parasites and the other one caused by parasitic worms (helminths) will be considered. These two infections illustrate why many parasitic infections are a serious and continuing public health problem.

Malaria. The impact of malaria, caused by protozoan parasites of the genus Plasmodium, on world health, and the life-cycle of malaria parasites in their human and mosquito hosts. Natural innate resistance to malaria in human populations living in disease endemic areas. Malaria Morbidity, patholgenesis, pathogenetic processes, and morbidity in the human, and cerebral malaria, caused by Plasmodium falciparum.

Key Examples of Parasitic Diseases: Schistosomiasis: Professor D Dunne

The distribution of chronic infections with parasitic trematode worms of the genus Schistosoma and their association with water in tropical and sub-tropical regions. The biology and life-cycle of schistosomes in their mammalian and freshwater snail hosts. The problem of controlling schistosomiasis in endemic areas with continuing susceptibility to reinfection after chemotherapeutic cure. The hepatic and urogenital morbidity associated with intestinal and urinary schistosomiasis respectively.

Parasitology: Encounter and Survival: Professor D Dunne

The problem of controlling of the diseases caused by microparasites and macroparasites in relation to their basic biology, and their status as ‘Diseases of Poverty’ and ‘Neglected Tropical Diseases’, in the context of the Millennium Development Goals.

The Immune System against Pathogens: Dr A Kelly

The immune response as an integrated system of defence against different pathogen groups.

Anaemia: Professor N Coleman

Anaemia is a clinical endpoint of multiple pathologies affecting red blood cells and/or their precursors. This lecture will consider some of the main causes of anaemia, including both genetic and environmental processes that reduce the production of red blood cells or increase their loss/destruction.

 Vascular Reactions to Injury:  Professor N Coleman

This lecture summarises the normal biology of haemostasis. It then describes the mechanisms by which haemostasis can be inappropriately activated leading to thrombosis and embolism. The roles that endothelial cells, platelets, altered blood flow and the coagulation cascade play in thrombosis will be examined. Finally, the clinical consequences of thrombosis and embolism will be introduced.


Atherosclerosis:  Professor N Coleman

This lecture summarises the normal biology of arterial walls.  It then explores how normal artery walls are altered in atherosclerosis.  It will discuss the epidemiology and aetiology of atherosclerosis including positive and negative risk factors.  Then, the cellular and molecular pathology of atherosclerosis will be explored with emphasis on the roles played by lipoproteins, endothelial cells, smooth muscle cells, platelets and leucocytes.  Finally, the lecture will briefly introduce the clinical consequences of atherosclerosis.


Ischaemia, Infarction and Their Results:  Professor N Coleman

This lecture will firstly consider the various causes of inadequate blood supply to organs, followed by an exploration of the cellular consequences and the factors that influence outcome in affected tissues. Next, the lecture will consider the reversible and irreversible changes induced by ischaemia, including the stages of a developing infarct. The lecture will conclude with specific examples of infarction affecting key organs, such as the heart, brain and lungs.


The nature of cancer: Dr P Edwards

Cancer as a disease. Brief introduction to cancer as failure of cell to participate in organisation of tissue as a result of altered genes. The distinction between benign and malignant tumours. Invasion and metastasis. The multistep nature of cancer development.  Colon and cervix cancer as examples. Tumour nomenclature. Incidence. How cancer causes disease and death. Presentation and screening. 

Cancer as an evolutionary process: Dr P Edwards

Cancer develops by Darwinian evolution and clonal expansion. Oncogenes and tumour suppressors, using as example the Rb-1 pathway (controlling G1/S checkpoint) and p53. Concept of genetic instability and its possible mechanisms: DNA repair defects, replication errors and mitotic errors. Hereditary predisposition to cancer including APC, BRCA2 and mismatch repair deficiency.


Cancer mechanisms: Dr P Edwards

The changes in cell behaviour in cancer, epitomised by the Hallmarks of Cancer concept (praticularly the original 2000 version). Control of proliferation, including major signaling pathways; apoptosis; senescence and other stress responses, telomeres. Stem cell concepts and how they illuminate cancer, particularly in reference to leukaemias and differentiation blocks. Mechanism of metastasis (largely unknown and controversial). 


The cancer genome: Dr P Edwards

What sorts of gene get mutated and what sort of mutations they suffer, from chromosome translocations to point mutations, and how they alter the function of target proteins, cells and tissues, using in vitro and animal models. The complexity and variability of cancer genomes. Technology of genomics. Epigenetic ‘mutations’.


Causes of cancer: Dr P Edwards

The incidence of most cancers varies dramatically between different populations, and this is apparently due mainly to environment, rather than genetics.  Chemical carcinogens and their activation by metabolism; radiation and infectious agents. Attempts to identify carcinogens and quantitate their potency.


Cancer therapy: Dr P Edwards

A forward-looking survey of the prospects for cancer therapy.  Classic cytotoxic therapies and how they might work. Targetted therapies, including anti-tyrosine kinases and anti-genetic instability approaches exemplified by PARP inhibitors. Resistance mechanisms.  Engineering viruses to kill cancer cells. Exploiting immune system via attempts to block tolerance.


Lent Term 2016 and Easter Term 2016

The Future of Disease – New Threats, New Insights

Virus Evolution and Host Resistance & Factors Driving Disease Emergence: Dr C Smith

How viruses originated and how they evolve, as well as the sources, mechanisms and consequences of novel viral disease emergence, including agents like Ebola, will be examined.

Emerging Protozoan Zoonoses I - Leishmaniasis: A complex Neglected Tropical Disease: Dr J Ajioka

Leishmania species cause a wide range of pathologies in both animals and humans depending upon the parasite-host combination and host physiological/immunological status. The disease is transmitted by sandfly vectors where the human pathologies have been generally classified as cutaneous, mucocutaneous and visceral. Visceral leishmaniasis caused by L. donovani and L. infantum results in death if not treated and many cases go unrecognized. Looking at leishmaniasis overall, a recent WHO update highlights the complex epidemiology, ecology and lack of easily-applied management tools as problems in understanding what is estimated to be the ninth largest disease burden amongst infectious disease.

Emerging Protozoan Zoonoses II - Toxoplasma as a model for the evolution and emergence of a global zoonotic pathogen: Dr J Ajioka

Toxoplasma gondii is a ubiquitous protozoan parasite that infects virtually all warm-blooded animals including humans with varying degrees of pathogenicity predicated on the parasite strain type, host species and host physiological/immunological condition. Humans for example, suffer only mild symptoms from infection unless they are a developing foetus or are immunosuppressed. By contrast sea otters are highly susceptible to disease due to T. gondii infection as are mice, depending upon the strain type. Population and evolutionary studies suggest that T. gondii populations has gone through at least two major bottlenecks since diverging from its closest relatives, the first 1-2 million years ago and the second about 10.000 years ago. Both the induction of host behavioural changes and variability via recombination in pathogenicity determinants like secreted kinases are major points of natural selection that shape the current T. gondii population and will produce new variant parasites and associated disease.

Evolution of Pathogenic Bacteria: Prof J Parkhill

Unlike eukaryotic organisms, bacteria can transmit genetic information both vertically and horizontally. Horizontal exchange occurs through three mechanisms: transformation, transduction and conjugation, and all of these have acted in various bacteria to create extant pathogenic lineages. Horizontal sharing of genes within bacterial species is sufficiently common to give rise to the “pan-genome”, the set of genes present in the whole species, only a subset of which is present in any representative. Accessory genes within this pan-genome can be key determinants of the pathogenic niche. Finally, genetic decay can play an important part of adaption to particular niches, and this is commonly seen in recently-evolved pathogens.

Emerging and Re-emerging Bacterial Disease: Dr N Brown

Throughout history, the incidence of different infections has waxed and waned. ‘New’ infections continue to be identified. The term ‘emerging infection’ has been defined as a new, re-emerging or drug-resistant infection whose incidence has increased in the past two decades, or threatens to increase in the near future. This phenomenon is a result of the complex interaction between microbial virulence, population susceptibility and factors that affect the various routes of transmission. This lecture will demonstrate some of these issues using the emergence and spread of different strains of Staphylococcus aureus as an example. It will also review the emergence of multiple antibiotic resistance in Gram-negative bacteria, such as Escherichia coli and Klebsiella pneumoniae, which is now considered to be a major threat to modern healthcare.

Genetic Disease - Haemoglobinopathies: Dr C Sargent

Students have been introduced to haemoglobinopathies as major causes of anaemia. In this lecture, the molecular defects will be studied in greater depth. Haemoglobin loci were amongst the first to be widely characterised by molecular biologists. The organisation of the globin loci, developmental regulation of gene expression, and functional differences between haemoglobins enable greater understanding of the impacts of genetic mutations. Worldwide, these mutations affect between 5-7% of the population, making the haemoglobinopathies the largest group of inherited genetic diseases.

Genetic Disease – Muscular Dystrophies: Dr C Sargent

The Duchenne muscular dystrophy gene on the X-chromosome was the first to be discovered using reverse genetics. Since the initial identification of the locus, the complexity of the gene transcription has become apparent. There are at least 30 known transcripts, generated from different promoters plus alternative splicing of the major RNA products. An understanding of the functional significance of the proteins encoded at the DMD locus elucidates the impacts of the broad spectrum of mutations listed in the mutation database. Furthermore, interactions with the dystrophin containing complexes reveals the relationship with other forms of autosomal dominant and recessive muscular dystrophies.

Exploiting Genetics: Diagnosis and Therapy: Dr C Sargent

The genetic bases of the haemoglobinopathies and muscular dystrophies are well known. This allows tailoring of diagnosis, screening and therapies based on the nature of the mutations. For the haemoglobins, population based approaches to screening are feasible, given the high incidence of mutant alleles in parts of the world affected by malaria. For X-linked DMD, the rate of de novo mutation requires a different approach, based on pedigree analysis. For both disease types, new treatments that exploit our knowledge of genetics are fast becoming feasible both for novel pharmacological intervention or gene-therapy.