This programme is centered around four research themes and information on individual supervisors' research areas can be found be following the page links.
Supervisors’ interests span molecular mechanisms that regulate the behaviour of cells in whole organisms through to the assembly of molecular machines in the cell that carry out basic cellular processes. This brings together scientists from the Divisions of Cell and Developmental Biology, Computational Biology and Gene Regulation and Expression (GRE). Researchers investigate the mechanisms of differentiation in developing organisms, stem cells and adult tissues and how these are corrupted in disease states. At the level of individual cells, research is focused at establishing mechanisms of chromosome duplication, mitosis, meiosis and understanding how gene expression is controlled. Frequently this incorporates large-ˇscale collection of imaging, proteomic and genomic data requiring rigorous computational and statistical analysis. Expertise is provided by scientists with skills in developing and applying computational, mathematical and biophysical techniques to address questions in biological and medical research. Examples include software such as Jalview (Barton group) and Open Microscopy Environment (OMERO) (Swedlow group) to interrogate and gain maximum value from the data collected.
Many of the transitions in cellular behaviour are driven by changes in the post-translational modification of proteins. These modifications can be with small chemical entities such as phosphorylation or N-ˇAcetyl Glucosamine or with small proteins such as ubiquitin or SUMO. The MRC Protein Phosphorylation and Ubiquitylation Unit (PPU) is a major research centre for understanding the biological roles of phosphorylation and ubiquitylation, while researchers in GRE study GlcNAc and SUMO modification. Multiple supervisors investigate the biological outcomes of modification using appropriate animal models and have developed proteomic pipelines to facilitate high throughput identification of modification sites. Establishing the mechanisms of modification is an important objective and this is tackled using structural biology, biochemistry and single molecule approaches. As disruption of these processes cause human diseases such as neurodegeneration, cancer, hypertension and immune disorders these pathways are important targets in the search for therapeutics.
This theme brings together cutting-edge research in Immunology and Infectious Disease and involves scientists from the divisions of Cell Signalling and Immunology, Molecular Microbiology and the Wellcome Centre for Anti-Infectives Research (WCAIR). The immunology work is relevant to the pathologies associated with cancer, diabetes, infectious disease, autoimmunity and allergy. Engineered animal models allow precise questions relating to defined biological pathways to be addressed in vivo. Use of high throughput proteomics has identified changes to protein levels and protein modifications that take place in immune cells in response to infection. Work in microbiology spans from fundamental science using model organisms to translational research on medically and economically significant pathogens. The overarching purpose is to generate excellent, innovative and internationally-recognised research on: molecular determinants of bacterial virulence; host responses to microbial pathogens;; fundamental physiological processes in microbial cells, including transport and generation of the cell surface; inter-bacterial interactions;; and identification of potential targets for antimicrobial intervention and biotechnological applications.
The extensive portfolio of our basic mechanistic science generates many opportunities for these discoveries to be translated into useful therapeutics. The role of the Drug Discovery Unit (DDU) is to translate basic science into lead compounds to validate putative drug targets. These chemical entities are used as tools to investigate disease pathways and, where appropriate, taken forward as pre-clinical drug candidates. Research interests of the DDU are focused on “Neglected Tropical Diseases” and “Innovative targets and pathways”. The DDU has all of the capabilities required for early phase drug discovery: assay development, high throughput screening, cell biology, medicinal chemistry, structural biology, computational chemistry and DMPK. All of these capabilities operate under one management structure to ensure an integrated approach and rapid progress. The drug discovery capabilities of researchers in Life Sciences are enhanced by the presence of the National Phenotypic Screening Centre (NPSC). This is an advanced high throughput facility that focuses on the development and screening of physiologically-relevant assays to tackle human, animal and plant diseases.