Introduction
Since the development of the "germ theory of disease" in the mid-1800s, a spectrum of microorganisms have been identified as the causative agents of many infectious diseases. Pathogenic bacteria, protozoan and metazoan parasites have threatened human and animal health throughout recorded history and remain major causes of illness worldwide. These pathogens undergo rapid genetic change and evolution, and are subject to intense selection pressure arising from the use of chemotherapeutic drugs and vaccines. As novel variants of these agents arise, the danger of less controllable disease is increasing not diminishing. In particular, emerging multi-drug resistance threatens to overwhelm our capacity to control infections. Thus, although substantial progress has been made in combating disease, there are reasons to believe the threat of infection may intensify in future. Consequently, there is a vital need to further increase our understanding of both the basic biology of pathogenic organisms and the concomitant host immune responses to them. In turn, this will underpin the development of new drugs, vaccines and vaccine delivery systems.
The Course
The Microbiology and Parasitology Option focuses on the mechanisms that underlie diseases caused by a number of important bacteria, protozoa and helminths. Agents of communicable disease that lie at the forefront of current research efforts or represent major neglected diseases of mankind are discussed, although the course is not constructed around a taxonomic approach. Emphasis is placed on the combined use of molecular, cellular and structural biology to unravel detailed structure-function relationships underlying pathogen-host interactions. The course also adopts a broader biological approach and addresses issues relating to epidemiology, vaccine development and chemotherapy. Sufficient background is covered to enable students to appreciate how host responses to parasite infections can result in useful immunity and sometimes in harmful immunopathology. Additionally, disease control projects in Africa linked to members of the Division are used to illustrate contemporary issues in the control of infectious diseases.
Research Projects
There is a diversity of research interests of the Division. Research in Microbiology is concentrated on elucidating molecular mechanisms that underlie the virulence of pathogenic bacteria. This work involves the study of toxin secretion, the interaction of toxins with mammalian target cells, studies of how bacteria invade mammalian cells and subvert their function, the regulation of virulence gene expression, and bacterial cell motility and multicellular behaviour. These studies thus encompass molecular biology, cellular biology, biochemistry and structural biology. Parasitology consists of research on protozoan and helminth infections and their subsequent host-immune responses. Work is in progress on the analysis of the genomes of the protozoan parasites Toxoplasma gondii and African trypanosomes, and the application of genomics to the investigation of the molecular basis for drug resistance, virulence and infectivity. Helminth research is concentrated particularly on schistosomiasis. Laboratory studies are combined with extensive human population-based fieldwork in Kenya and Uganda. These studies are focused on the immuno-epidemiological factors that control infection and transmission and human morbidity.
Research projects are available which cover a wide range of topics, and students are almost always able to match a topic to their own particular interests. Other scientists in laboratories whose work is closely related to the Division's, such as members of staff of the Public Health Laboratory, also contribute projects.
Examples of Current/Previous Projects
2016-2017 Projects
- Investigating hookworm regulation of IgE mediated responses
- Bacterial manipulation of the host actin cytoskeleton
- Transformative effects of parasitic nematode proteins on mammalian cells
- Analysis of expressed variant antigen sequences from Kenyan children with malaria
- Engineering E. coli export pipes: a new platform technology for the synthesis and one-step secretion of therapeutic proteins
- Impact of Toxocara cati infection on the composition of the feline gut microbiota
- Models for the within-host dynamics of bacterial infections
- Design, expression, and purification of hexahistidine-tagged bacteriophage FX174 proteins for in vitro infectious virion assembly.
- Investigating the interaction between ARIH2, a human E3 ligase, and TsUBE2L3, an E2 conjugating enzyme secreted by the parasite Trichinella spiralis.
- Remodelling of the cytoskeleton by the bacterial pathogen Salmonella.
- Investigations into sequence networks of Plasmodium falciparum var genes and the genetic structuring of group A var subtypes associated with differing severe clinical symptoms.
- Intoxication of mammalian host cells by the typhoid toxin of Salmonella Typhi.
- Investigating F1hB variants that cause spontaneous specificity switching of the bacterial flagellar export machinery.
- An investigation into hookworm regulation of IgE mediated responses to hookworm, dust mite and S. mansoni antigens in a Ugandan case-control cohort.
- Investigations of parasite-host-microbiota interactions using cutting-edge genomics and bioinformatics technologies.