The scientific research focus of the Centre is the study of molecular mechanisms underlying important aspects of bacterial physiology and pathogenesis, as well as host immune processes. The research covers six broad themes:
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Genetic basis of virulence
A combination of genomics and mutagenesis studies are employed to manipulate bacterial pathogens. The aim of this work is the identification and characterisation of genes that contribute to the virulence and spread of microbial pathogens. We collaborate with the Wellcome Trust Sanger Institute which has world leading expertise in pathogen genomics.
Cellular microbiology refers to studies on the intimate relationship between bacterial pathogens and host cells. It has become a very exciting field which has revolutionised our understanding of how pathogen effector proteins subvert host cell processes for their benefit. Several groups in the CMBI are studying the cellular microbiology of pathogens such as E. coli, Legionella, Salmonella, Mycobacteria, Chlamydia and Shigella.
The CMBI has a strong interest in the development of novel vaccines and therapeutics. Several vaccine candidates have been developed by members of the Centre against conditions such as typhoid fever and bacterial meningitis. Some of these are currently undergoing clinical trials. Work on essential bacterial activities such as biogenesis of the cell wall and DNA transcription are providing novel targets for antimicrobial drugs.
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Structural characterisation of molecules that contribute to
There are close links between the CMBI and the Centre for Structural Biology that enable structural analysis (crystallography, NMR, mass spectrometry, cryo-electron microscopy, modelling) of key microbial virulence factors. This structural information is combined with biochemical approaches to identify novel therapeutic molecules.
Antibiotic resistance and persistence
There is an increasing need to study the molecular basis of the emergence and spread of antibiotic resistance, as well as the phenomenon of persistence, in which bacteria show tolerance or insensitivity to antibiotic treatment, sometimes through the establishment of biofilms. Through developing an understanding of biochemical pathways and mechanisms underlying the formation of persisters and their re-growth, it might be possible to prevent them from entering into, or force them out of, a persistent state, thereby rendering them sensitive to antibiotics.
Host innate immunity, bacterial discrimination and tolerance
An understanding of pathogen-host interactions requires the study of both pathogen and host. Existing work on intracellular innate immune mechanisms will be strengthened by the establishment of new groups to work on complementary areas of innate immunity, such as the mechanisms by which the host mucosa discriminates between pathogens and commensal bacteria to establish tolerance.