mTORC1

Mechanistic target of rapamycin complex 1 (mTORC1) is a protein kinase that essentially ‘senses’ the availability of mitogenic (pro-growth) signals. The presence of amino acids and growth factors activate mTORC1 to drive the production of biomass including new proteins and lipids.

The activity of mTORC1 is controlled by dynamic, nutrient-dependent changes in the subcellular localisation of its regulators, particularly between the cytoplasm and the lysosome. We are using proteomics, live cell and high-resolution imaging to investigate the mechanisms controlling these protein movements.

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Autophagy

Macroautophagy (or simply autophagy) is a cellular recycling process that occurs at basal levels in all cells but is largely inhibited by active mTORC1. Autophagy functions to sequester damaged and potentially toxic cellular components such as protein aggregates and entire organelles and deliver them to the lysosome for degradation. Autophagy is rapidly upregulated upon mTORC1 inhibition, such as during starvation, to scavenge nutrients and ensure cell survival.

In the lab, we are using cell biology and biochemistry to investigate how the nutrients liberated via autophagy are sensed and used to fuel the cell and what the repercussions are when this degradative pathway goes wrong.

Senescence

One of the major projects in the lab is to understand the molecular basis for dysregulation of mTORC1 and autophagy in cellular senescence. Senescence is a potent tumour suppressor mechanism and has a close association with some cancers, such as melanoma. The accumulation of senescent cells is also an established driver of tissue and organismal ageing.



mTORC1 is a well-known driver of many senescence phenotypes and targeting its activity is a promising strategy to combat age-related disease. By working to dissect how the mTORC1-autophagy pathway is deregulated, we will also identify new targets that can be exploited in the development of future therapeutics.

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School of Biochemistry
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