Presentation description

Amino acids play an essential role in cell metabolism as the building block of proteins. It is known that amino acid deficiency in cells causes the cell to initiate autophagy, however it is not well understood how they react to elevated amino acid conditions. Research suggests that elevated levels of amino acids are deleterious to the cell and organismal health, however there is little understanding of how this amino acid toxicity affects metabolic and transcriptional systems in the cell. Certain metabolic disorders such as diabetes and citrullinemia have been associated with elevated levels of amino acids; however, many of these metabolic disorders do not have effective treatments beyond dietary restrictions which is why it is important that we understand how amino acid affects metabolic systems. In order to identify proteins involved in evading amino acid toxicity, we generated a library of suppressor strains that resist toxicity. Suppressors are cells that developed a mutation which allows them to grow in conditions that would otherwise be lethal such as high concentrations of amino acids. We generated this suppressor library by plating cells susceptible to amino acids onto high concentrations of each amino acid and selecting colonies that were able to survive those conditions. We then tested all of these strains on high concentrations of amino acids to determine their ability to resist toxic amino acid concentrations. Those that were able to resist the toxic effects of some amino acids, but not all amino acids were selected for further genetic, metabolic, and transcriptional analysis to identify pathways involved in ablating the toxicity of specific amino acids. The aim of this research is to investigate how amino acid toxicity affects the metabolic and transcriptional cell systems of budding yeast in order to create new therapies for metabolic disorders.