Grant: Operating Grant

Understanding how gene regulation is controlled, and how cells interpret their own genome, is one of the great challenges of our era. Gene expression - the process of turning genes and their products on and off - is controlled by the joint activity of hundreds of proteins that recognize specific DNA and RNA sequences present in or encoded by the genome. These proteins work together in ways that are largely uncharted, executing programs such as development, differentiation, homeostasis, and cell reprogramming, but also aging and disease. The details of how these processes work remain extremely difficult to decipher because of the complexity of cells, and this limits our ability to understand, harness, diagnose, and fix biological systems. As with any type of problem, if one does not know how the system works, it is impossible to make rational decisions, and the results of any intervention will be unpredictable. In order to change medicine and biotechnology into disciplines driven by principles and basic knowledge, rather than by trial-and-error, we need to understand how all of the parts controlling cells work, and how they work together. We make use of a powerful model system -- the budding yeast -- to explore regulators of gene expression. We have also developed and applied new technologies that have enabled us to understand aspects of gene regulation that have so far been elusive. We expect our studies of gene expression in model systems to provide conceptual, and ultimately practical, approaches to disease treatment.