Regulation of the ER Stress Response by Amino Acids

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The long term objective of this research program is to determine how individual building blocks of proteins (i.e., amino acids) control adaptive survival responses in cells. In this proposal, we investigate how the availability of amino acids controls the 'endoplasmic reticulum stress response', an ancient cellular process that controls the balance between life and death. We predict that the availability of amino acids will modify the function of 'endoplasmic reticulum stress' transcription factors and genes that regulate cell death. The short term objective of this research proposal is to identify and characterize the proteins required for amino acids sensing during the endoplasmic reticulum stress response, and how they are modified by amino acid depletion. We will use sophisticated biochemical and molecular biology techniques to measure the effect of amino acids on the modification and levels of endoplasmic reticulum stress proteins, and on cell death. Our studies will reveal new mechanisms by which nutritional components control cellular adaptive responses to stress, and how cells make decisions about their survival.**