Biofilm formation is the process by which single celled microbes form an adherent community. Bacillus subtilis is a Gram-positive bacterium that lives in the soil and can form biofilms on the roots of plants. In this environment the bacteria stimulate growth of the plant and therefore theoretically can function as an alternative to petrochemical derived fertilisers. The resident bacterial cells synthesize a extracellular matrix containing protein, DNA and polysaccharides that surrounds and protects the cells in the biofilm.
Wellcome Trust 4-Year PhD Programme
In order to maintain genetic stability and prevent the amplification of chromosome segments, the process of DNA replication occurs in two strictly non-overlapping phases. In late mitosis and G1, replication origins are ‘licensed’ for replication by being loaded with double hexamers of MCM2-7 proteins. Then, during S phase, replication forks initiate at these licensed origins. Defects in regulation of the licensing system are associated with a variety of diseases including cancer and growth disorders .
Collective cell migration – a process in which cohorts of cells move as a group while maintaining their mutual connections with each cell coordinating its movement with its neighbours – is a fundamental process in development and tissue regeneration. Aberrations that lead to cells acquiring migratory abilities, known as invasion, are displayed in many invasive tumour types. At the cell level, molecular processes that control cell’s migratory properties are related to the cytoskeleton, i.e., mainly to the actomyosin network and signalling pathways that control it.
We investigate the regulation and function of the mRNA cap, a modification of RNA essential for gene expression which integrates transcript processing and translation. We are beginning to understand how oncogenes and signalling pathways can regulate gene expression via regulation of mRNA capping enzymes. Signalling pathways which modify the mRNA capping enzymes have the potential to change the gene expression landscape, thus causing changes in cell physiology.
Toll-Like Receptors are activated by substances produced by microbial pathogens, such as lipopolysaccharide (LPS), a component of the cell wall of gram-negative bacteria. This induces the formation of the Myddosome, a multi-protein complex, which recruits and activates at least three E3 ubiquitin ligases, termed TRAF6, Pellinos and LUBAC. These E3 ligases then generate hybrid ubiquitin chains containing both Lys63- and Met-1-ubiquitin linkages.
To maintain their genetic integrity, eukaryotic cells must properly segregate their chromosomes to daughter cells during their cell division cycle. The unraveling of the mechanisms for chromosome segregation should improve our understanding of various human diseases such as cancers and congenital disorders, which are characterized by chromosome instability and aneuploidy. To study chromosome segregation, we use budding yeast and human cells as model systems. Overwhelming evidence suggests that the basic mechanisms of chromosome regulation are well conserved from yeast to humans.
Many bacterial pathogens use the Type VI secretion system (T6SS) nanomachine to fire toxic ‘effector’ proteins directly into target cells. It is becoming increasingly apparent that the T6SS plays a key role in the virulence and competitiveness of diverse Gram-negative bacteria, including important human pathogens. Pathogens can use T6SSs to directly target eukaryotic organisms, as classical virulence factors. Alternatively, many pathogens can use T6SSs to target other bacterial cells, killing or inhibiting rivals.
The Findlay lab employs cutting-edge technologies to unravel Embryonic Stem (ES) cell signalling networks (Williams et al, Cell Rep 2016, Fernandez-Alonso et al, EMBO Rep 2017; Bustos et al, Cell Rep 2018), culminating in our recent discovery of the ERK5 pathway as an exciting new regulator of ES cell pluripotency. In order to uncover functions of ERK5 in ES cells, this project will deploy global proteomic and phosphoproteomic profiling. Novel ERK5 substrates and transcriptional networks will be characterised using biochemical and ES cell biology approaches.
Membranes and their protein organization are a frontier in our understanding of cell biology. We focus on polarized trafficking as a model to uncover fundamental mechanisms in the organization of structures at membranes. We aim to understand the role of protein complexes including the exocyst. This project seeks to answer mechanistic questions regarding 1) the regulation of protein structural mechanics in polarized trafficking, 2) and the consequences of signalling on this pathway and its organization.