Interplay between the exocyst complex and Tor signal transduction in the fission yeast Schizosaccharomyces pombe

Regulation to ensure correct growth and development is paramount for the survival of every organism. For cellular homeostasis to be maintained, cells have evolved with ever more complex processes that regulate growth and division. All these processes involve the sensing of the environment for nutrients or stressors. Stressors affect specific proteins in the plasma membrane which act as molecular switches to turn on stress signalling pathways to reduce growth of the organism. Conversely, nutrient rich environments promote growth through the nutrients themselves activating signalling networks that promote cellular growth.

Once activated, these signalling networks control cellular processes involved in modulating cell growth and size. One of these includes intracellular trafficking. Both exocytosis and endocytosis play key roles in the delivery of materials needed to protrude the cell periphery, but also the removal nutrient transporters, receptors, and lipid domains in the plasma membrane so that growth occurs in the correct cellular location and at a regulated rate. One trafficking complex that has been implicated in both exo- and endocytosis is the exocyst complex.

The exocyst is a conserved hetero-octameric complex that is thought to tether cargoes to the plasma membrane. While most of these exocyst related cargoes are still awaiting identification, proteins involved in nutrient uptake have been shown to be dependent on exocyst mediated exocytosis. Mutation of exocyst members also results in defects in endocytosis, revealing a role for this complex in the retrograde transport of these components too. Furthermore members of the exocyst have been implicated in the activation of stress signalling pathways. This places the exocyst as a potential master regulator of stress and nutrient sensing via its modulation of the level of stress and nutrient sensors at the cell surface and possible bridging of this to signalling networks.

A PhD student will test the hypothesis that the exocyst complex is involved in nutrient sensing through regulation of Tor signalling. They will tackle this question using a combination of genetics, cell biology and biochemical techniques, and by exploiting the experimental power of the fission yeast S. pombe.

The PhD student will tackle this question by exploiting the experimental power of the fission yeast S. pombe in conjunction with vertebrate neuronal cultures. Using a range of genetic, biochemical and fluorescent imaging techniques the PhD student will use yeast to identify the partners of the exocytic system in actin organisation and apply the conclusions to vertebrate neurons. Due to their inherent complexity, variations in neuron morphology are currently practically impossible to assess. An automated image processing framework will be developed to objectively extract morphological information from fluorescent images of the cells' borders, from which quantitative conclusions may be drawn. This tool will help probe features of cell shape across classes of organism. All in all, these data will provide novel insights into a universal mechanism that is utilised throughout evolution, in fungi, plants and animals.