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

所有活着的生物体都发展出了复杂的调节机制，以帮助在营养匮乏或饥饿期间维持其生存能力。该实验室的中心目标是了解新陈代谢变化如何影响细胞的生物功能，并确定细胞如何应对营养缺乏。为此，我们正在研究一种进化上保守的氨基酸“感应”蛋白质复合体的生物学功能，这种复合体存在于酵母和人类之间。通过未知的机制，这种复合体可以感觉到细胞内氨基酸的丰度，并协调细胞程序，控制氨基酸并入蛋白质或转化为其他生物分子。有趣的是，我们发现抑制这种氨基酸传感器也可以改变细胞处理碳水化合物的方式，比如葡萄糖。我们的研究旨在确定细胞如何整合这些基本代谢物的利用，并定义营养排队影响细胞通讯程序以维持代谢平衡的新机制。我们希望这些研究将为新陈代谢的重要调控机制提供新的见解，并开发针对细胞代谢变化的新方法。

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.