Mechanistic Studies of Amino Acid Homeostasis and Organellar Crosstalk by GATOR1.

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All living organisms have developed intricate regulatory mechanisms to help maintain their viability during periods of nutrient deprivation or starvation. The central goal of the lab is to understand how metabolic changes can influence the biological functions of cells and determine how cells cope with nutritional deficiencies. To this end, we are investigating the biological function of an evolutionarily conserved amino acid-“sensing” protein complex that is present from yeast to humans. Through unknown mechanisms, this complex can sense the abundance of amino acids inside the cell and orchestrate cellular programs that control amino acid incorporation into proteins or conversion into other biomolecules. Intriguingly, we have found that inhibiting this amino acid sensor can also change how cells process carbohydrates, like glucose. Our studies aim to determine how cells integrate the utilization of these fundamental metabolites and define new mechanisms by which nutrient queues influence cellular communication programs to maintain a metabolic balance. We hope these studies will provide novel insights into important regulatory mechanisms of metabolism, and develop new ways to target metabolic changes in cells.