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Molecular cell biology

Cell cycle, chromosomes and gene expression; cell signalling, receptors and signal transduction

This is a core research theme that is important across the School and links with many other themes. The cell cycle, chromosomes and gene expression work links to the global analyses of gene expression at the epigenetic and post-transcriptional levels in the functional genomics and systems biology, development and stem cell biology, and plant biology themes. The cell cycle and DNA repair work is strongly related to cancer research. Some recent research is highlighted here.

Cell cycle, chromosomes and gene expression

A thirty-year old question as to of how the rapid division of early embryos slows down at the mid-blastula transition (MBT) has been solved. It has been shown that this is through the titration of four limiting replication factors. Altering the amounts of these factors can advance or delay the MBT, with profound effects on development. Novel insights into regulation of the DNA damage response by ubiquitin and ubiquitin-like modifiers has led to the formation of a new company Mission Therapeutics, based on the concept of synthetic-lethality to target cancer cells.  It has been demonstrated that hyperedited inosine-containing RNA potently antagonizes the interferon response and the role of piRNAs in multi-generational epigenetic memory has been found.

Cell signalling, receptors and signal transduction

There is particular interest in the assembly and function of receptors, including Cys-loop, Toll-like receptors, collagen receptors, P2X and other ionotropic receptors. Major progress has been made in understanding signalling downstream of receptor activation, including compartmentalization of cAMP generation and utilization, inositol trisphosphate (IP3) signalling and kisspeptin signalling, and work on intracellular trafficking and cell-cell interaction. Some recent findings include the demonstration that IP3-induced clustering of its receptors retunes their sensitivity to both IP3 and Ca2+. Other work has shown that phosphatidylinositol 4-phosphate (PI4P) contributes to the pool of polyanionic lipids that define plasma membrane identity.

This work benefits from continual investment in cutting-edge facilities and infrastructure, such as imaging and proteomics. In particular, single molecule imaging methods will increasingly be used to address problems in cell signalling.