Research theme: Molecular Biology

The Molecular biological research theme has three main areas: infection and immunity, genomics and cell signalling.

Infection

Infection remains of central importance in medicine as the leading cause of premature death worldwide. Researchers in the medical school focus the major health priority of the evolutionary biology of antibiotic resistance, seeking to understand the factors that drive resistance and the fitness barriers that organisms have to overcome. This includes basic laboratory experimentation and research in collaboration with health service partners. This work has enable SNP specific mutation rates to be identified and reproducible assays to monitor bacterial fitness to be developed.

Using these tools our aim is to be able to predict the capacity of resistant organisms emerging in the hospital and community to survive and cause disease. Other research focuses on virology and antiviral drugs and significant contributions have bee made to research into the development of the HIV-1 maturation inhibitor bevirimat. Further work will develop novel inhibitors of influenza neuraminidase and haemagglutinin proteins in collaboration with colleagues in biology and chemistry.

Tuberculosis is a major focus with a study of a novel treatment for tuberculosis that will shorten duration from six months to four. With more than 30 clinical trial sites in Africa, Asia and the Americas 1900 patients have been recruited and this study has established capacity and developed methodologies that will be used in future trials.

This work underpins studies in molecular biomarkers and mathematical modelling studies of treatment responses that are being performed in collaboration with Astrophysics. There is a developing theme in immunology where the role of MHC Class I antigen dimers in the pathology of ankylosing spondylitis is being studied.

Genomics

Genomics research is focussed around the molecular dissection of genetic associations with cognitive phenotypes and neurodevelopmental disorders. This involves mainly assessment of genetic variants on gene expression regulation. It also uses genetic analysis to identify novel candidate genes for neurodevelopmental disorders.

Another group has had considerable success in establishing novel sample the understanding of the pathogenicity of micro-organisms including the recently identified human pathogen Mycoplasma amphoriforme and evolution of antibiotic resistance in tuberculosis. This work is performed in collaboration with the Wellcome Trust Genome Campus. collections through different clinical collaborators in the UK and overseas.

Cell signalling

Cell signaling is an important focus with groups aiming to elucidation of new signalling pathways in humans and model organisms, which are of clinical and physiological significance. Key areas of interest within are calcium (inositol) and zinc signalling, and the regulation of ion, water and solute transport across epithelia.

Recent research highlights include the dentification of a novel fatty acid-zinc signalling system in the circulation, the identification of a novel neuronal calcium feedback pathway, characterisation of the role of inositol as an essential cellular osmolyte in vertebrates and the identification of a unique family of phospholipase C-like proteins. There is a growing interest in cancer biology with research ongoing on the role of the Hippo cell-signaling pathway in the oncogenesis of breast carcinoma.