Genetic Analysis of Signal Transduction with Reference to Type 2 Diabetes
We have automated a method to accelerate the identification of the intracellular paths that underlie cellular communication and pathogenic responses in the immune system. As part of that program we have created robotic approaches that allow the rapid identification of genes that control transcriptional activation, subcellular localization and receptor deactivation. We have also developed systems for rapid generation of mice bearing targeted disruptions of specific candidate genes. We are integrating the two approaches with an emphasis on signaling pathways that influence organismic responses to metabolic load and pathogens.
Several of the pathways that have been studied have been found connected with general mechanisms for maintaining energy homeostasis. A particularly prominent theme has been the interactions of genes that control immune responses and those that mediate the balance of catabolism and anabolism. An improved understanding of the factors that regulate inflammation and its influences on energy utilization may deepen our understanding of the traits that increase the risk for diabetes and the possible consequences of interventions directed against one or more of the gene products identified here.
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