Species from several fungal genera, including Candida, Aspergillus, Pneumocystis and Cryptococuss have the potential to give rise to serious clinical infections and are estimated to cause 1.5 million deaths per year. Despite their importance as human pathogens, our understanding of how they affect immune cells, and how this might be affected by the presence of other pathogens is incomplete.
Most of our food calories come from cereal grain. The development of cereal plants strongly influences the amount of harvested grain or its yield. Cereal stems elongate when they flower (1). Tall cereals easily fall over, a devastating event for farmers, so controlling cereal height is important for cereal breeders. We recently discovered that jasmonate, a classic plant stress/defense hormone, strongly inhibits both flowering and stem elongation in barley (2), suggesting that the jasmonate pathway may be a good breeding target.
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 quantitative phosphoproteomic, proteomic and transcriptomic (RNA-SEQ) profiling.
Ubiquitin proteasome system (UPS) controls protein turnover in cells in order to maintain cellular homeostasis (1). E3 ubiquitin ligases facilitate the process of attaching ubiquitin on sustrate proteins. By recruiting E3 ubiqutin ligases to the Proteins of Interest (POIs), we can target specific POIs for UPS-mediated degradation, for example by small molecule proteasome targeting chimeras (PROTACs).
Ubiquitin signalling, which involves the posttranslational modification (PTM) of proteins with ubiquitin, regulates almost every aspect of eukaryotic biology. This versatility is possible because proteins can be modified with different types of ubiquitin codes resulting in distinct functional outcomes. An indispensable role for ubiquitylation is to serve as a signal for the degradation of misfolded and damaged proteins. In addition to degradation, ubiquitin modifications can serve as distinct signals to facilitate intracellular communication.
To maintain genetic integrity, human cells must segregate sister chromatids to opposite spindle poles, prior to their cell division. Errors in this process cause cell death and various human diseases, such as cancers and congenital disorders, which are often characterised by chromosome instability and aneuploidy . Evidence suggests that chromosome instability is closely linked to the aetiology of several types of cancers. Moreover, due to chromosome instability, cancer cells rapidly change their phenotypes, which poses major therapeutic challenges.
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.
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 signaling on this pathway and its organization.
Intellectual disability (ID) and associated developmental delay are severe neurodevelopmental conditions that affect approximately 1% of the world population. 5% -10% of ID cases are due to mutations in genes located on the X chromosome. One of the genes shown to co-segregate with X-linked intellectual disability (XLID) in twelve patients is the gene ogt. Ogt encodes an essential enzyme, the O-GlcNAc transferase, which catalyses an abundant nucleocytoplasmic post-transcriptional modification O-GlcNAcylation.
Recruitment for our Wellcome 4-Year PhD Programme in Integrated molecular, cellular and translational biology is now open. Greater than 40 different supervisors participate with diverse research areas. Further information can be found on the programme website. Students on this programme will carry out three short laboratory placements prior to selection of main PhD project.