Department of Microbiology & Immunology
Research Topics - 1999
Enquiries: Dr S.Heaphy or individual supervisor
Dept. Head: Professor P.H. Williams
Tel 0116-252 2951
Fax 0116 252 5030
Email: sh1@le.ac.uk
| Home students: This Department has
no funded studentships available at present. |
| Overseas students: All inquiries from overseas must
be directed to higherdegrees@le.ac.uk.
They will supply an application form which should be completed and returned to them. |
The Department of Microbiology and Immunology comprises
of 15 academic members of staff, 19 postdoctoral fellows, about 20 graduate students
and 40 other support staff. It receives substantial support from the MRC, NERC, Wellcome
Foundation, Medical Research Charities, Health authorities and various industrial
sources. The main research areas include: (1) Microbial Systematics and Evolution;
(2) Microbial Physiology; (3) Molecular Aspects of Microbial Pathogenicity; (4) Virology,
including medical aspects; (5) Immunology; (6) Structure and Function of Macromolecules;
(7) Environmental Microbiology.
PROFESSOR P.W. ANDREW:
Email: pwa@le.ac.uk
Project: Bacterial pathogenesis
Streptococcus pneumoniae is the number one cause of bacterial pneumonia and is a major cause of meningitis. We are investigating a number of proteins produced by this bacterium. We want to understand their role in disease, how they work and how regulation of their genes is controlled. Understanding how these proteins work is allowing us to design new methods of therapy and vaccination. To do this research, we are using a range of recombinant DNA techniques, immunological methods and methods in protein biochemistry.
Mycobacterium tuberculosis is the cause of tuberculosis, one of the major diseases of man world-wide. We are using recombinant DNA techniques and immunological techniques to investigate how activated macrophages kill M. tuberculosis and how the bacterium attempts to avoid the killing mechanisms and adapts to survive in hostile in vivo environments. Development of high-throughput screening systems for identification of antimycobacterial drugs is also part of this work.
Listeria monocytogenes is a food-borne pathogen that can cause serious disease in man and animals. Food, in addition to being a nutrient, can represent a hostile environment for bacteria. We are using genetic and biochemical approaches to investigate how L. monocytogenes manages to survive and exploit the environments present in foods.
DR M.J. BROWNING:
Email: mjb22@le.ac.uk
Project: Cell mediated immune responses to infection and tumours
Research interests focus on T lymphocyte responses to infections (especially viral) and tumours. Current research topics include studies of T cell responses to human cancer cells, and mechanisms of enhancing tumour cell immunogenicity for stimulating T cell responses; and investigation of T cell telomere erosion and telomerase activation in response to infection and in aging. Projects employ a range of cellular and molecular mmunological techniques.
PROFESSOR W.D. GRANT:
Email: wdg1@le.ac.uk
Project: Environmental Microbiology
Ecophysiology of bacteria from saline and/or alkaline environments. Molecular systematics of halobacteria and alkaliphiles. Molecular methods applied to environmental microbiology.
DR S. HEAPHY:
Email: sh1@le.ac.uk
Project: Molecular microbiology
I am studying the process by which retroviruses, including HIV-1 form dimers of genomic RNA which are then specifically recognised by viral proteins and assembled into viral particles. I am also interested in identifying inhibitors of a bacterial RNA-protein complex called SRP. SRP function is essential for cell survival, it interacts with some proteins that associate with the bacterial cell membrane.
A second interest is the identification of microbial genes which express industrially useful enzymes directly from environmental samples such as sediment.
We use a wide variety of techniques in these studies ranging from the culture of pathogen agents, library construction and gene isolation, through to the biochemical study of purified RNA and proteins. Projects suitable for microbiologists, biochemists or molecular biologists are available.
References: M. Haddrick, A. Lear, A.J. Cann & S. Heaphy (1966). Journal of Molecular Biology 259, 58-68.
Maddison B, Marya P & Heaphy S (1998). Biochim et Biophysica Acta 1398, 305-314.
PROFESSOR S.H. MYINT:
Email: dsm@le.ac.uk
Project: Medical Virology
Mechanisms of viral-induced wheezing. Studies are taken both in vitro and in experimental volunteers to understand the pathogenesis of wheezing induced by common cold viruses. This is a multi-disciplinary project.
Antimicrobial properties of plants. Novel antiviral and antibacterial compounds are identified from plants around the world and developed into formulations for clinical trials in a fledgling phytopharmaceutical company.
DR K. NICHOLSON:
Email: kgn2@le.ac.uk
Project: Coronaviruses
The human coronaviruses OC43 and 229E are responsible for 10-20% of the acute upper respiratory tract infection and are implicated in asthma exacerbations in both adults and children. Given the frequency with which infusion with these two serotypes occurs it is evident that reinfection with OC43 and 229E serotypes occurs commonly, indeed this is borne out by longitudinal studies of patient cohorts. Sub-types of coronaviruses are probably responsible for their high 'reinfection' rates. The aim of this study is to characterise monoclonal antibodies raised against 229E and OC43, and subsequently to compare isolates of coronaviruses antibodies using an appropriate panel of monoclonals and cultures of human nasal epithelium.
PROFESSOR P.H. WILLIAMS:
Email: phw2@le.ac.uk
Project: Molecular and Cell Biological Analysis of the Virulence of Intestinal Bacterial Pathogens
There are three major areas of research interest in my laboratory, all concerning microorganisms associated with diarrhoeal disease in man.
Enteropathogenic Escherichia coli (EPEC) is a cause of severe persistent diarrhoea in infants, especially in developing countries. My interest in this organism is in its ability to mimic the effects of various growth factors and hormones whose normal function is the modulation of fluid and ion transport across the intestinal mucosa. Prolonged overstimulation of signal transduction pathways by EPEC results in extensive intestinal damage and eventually to enterocyte death, but the bacterial functions that induce such complex processes have not yet been fully explained.
Campylobacter jejuni has relatively recently been identified as a major human pathogen, causing severe inflammatory diarrhoea among children and young adults in developed countries. Symptoms resemble those of the inflammatory bowel diseases ulcerative colitis and Crohn's disease, for which no aetiological agent has yet been identified. My particular interest here is the mechanism by which Campylobacter stimulates inflammation and eventual tissue damage.
Salmonella species are a major cause of food-borne gastrointestinal illness in both developed and developing countries. Vaccines are available but inefficient. My interest is to apply well established evidence for the crucial role of iron in bacterial infections to developing a fuller understanding of iron uptake by Salmonella, and to constructing potential live oral vaccine strains attenuated in some aspect of their iron metabolism. In each case, modern molecular genetics and new techniques in cell biology are being used to analyse the nature and control of bacterial virulence factors and the host's responses to infection.
References: HA Manjarrez-Hernandez, TJ Baldwin, PH Williams, R Haigh, S Knutton, A Aitken. 1996. Infection and Immunity, 64: 2368-2370.
KG Wooldridge, PH Williams, JM Ketley. 1996. Microbial Pathogenesis, 21: 299-305.
R Reissbrodt, R Kingsley, W Rabsch, W Beer, M Roberts, PH Williams. 1997. Journal of Bacteriology, 179: 4538-4544.
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