Research Summary

Nutrient sensing and regulation of cell fate

Cells show a remarkable plasticity of fates, transitioning through cell growth, proliferation, differentiation, autophagy, quiescence and cell death. It is increasingly clear that the underlying metabolic state of the cell can directly determine cell fates. These distinct fates are regulated by “metabolic sensors”, which sense key metabolites. Therefore, in order to understand how nutrients and specific metabolites determine cell fate, it is essential to identify both the metabolic sensors and the pathways they regulate. Most of our current understanding of nutrient sensing and metabolic regulation come from cell culture models where cells either grow in abundant nutrients, or acute starvation. However, in most biological contexts nutrients are limited, but not entirely absent. During nutrient limitation, cells might divide, differentiate, undergo autophagy, or die. Our knowledge of how cell fates are determined under these conditions is poor. My lab is interested in understanding how cells sense nutrients (particularly amino acids), and regulate metabolism which in turn regulates distinct cell fates. To address this, we use a range of approaches combining biochemistry, genetics and cell biology with quantitative metabolomics and proteomics. Our current research focuses on questions addressing how amino acids are sensed, and how amino acid metabolism is regulated. Part of our lab investigates how metabolism and protein translation are integrated, and how modifications on specific tRNAs can control metabolic homeostasis. In other work, we seek to identify new metabolic switches that regulate amino acid dependent cell growth under different conditions. We are also exploring the metabolic basis of cellular cooperation, and facultative multicellularity in isogenic cell populations.

Figure Legend: Understanding the metabolic basis of cell fate decisions