GroseLab:Research

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GroseLab

  • Our lab is interested in the regulation of metabolism in response to the availability of nutrients and other factors affecting growth. We use model organisms, such as Saccaromyces cerevisiae (baker’s yeast) and Salmonella typhimurium, to study key pathways involved in metabolic regulation. Proteins and pathways are often conserved and thus our findings may aid in understanding metabolic regulation in other organisms, including humans. Our lab focuses on two aspects of metabolic regulation described below.

PAS kinase

  • The first is the study of PAS kinase, a highly conserved sensory protein kinase that is involved in the regulation of glucose metabolism in both yeast and mammals. The PAS kinase protein has both a sensory and a regulatory domain. The sensory component consists of a PAS domain that may bind small molecule effectors. The PAS domain regulates an attached serine/threonine protein kinase that then modifies other proteins in order to regulate cellular processes in response to certain stimuli. Our goal is to further characterize the role PAS kinase plays in metabolic regulation by identifying specific mechanisms involved in its activation and function. The yeast, Saccaromyces cerevisiae provides powerful genetic and biochemical tools for identifying PAS kinase related pathways and proteins.

NAD metabolism

  • The second aspect of metabolism we are studying is control of NAD and NADP levels within the cell. The vitamin niacin (B3) is a precursor to both NAD and NADP, which are essential for life in all organisms known. Together, these related cofactors serve in over 300 cellular reactions, several of which are central to basic metabolism. In addition to their roles as cofactors in metabolic reactions, NAD(P) also serve as allosteric regulators of many key metabolic reactions making control of NAD(P) levels critical to proper metabolic regulation. One of the key questions we are examining is why two very structurally related cofactor molecules have evolved (NAD and NADP differ by a single phosphate). It is thought these compounds arose in order to allow cells to differentially regulate metabolic process. In support of this hypothesis, NAD is primarily used for the production of cellular energy (ATP) while NADP is primarily used in reductive biosynthetic reactions that produce the molecular building blocks of the cell. Many of the pathways leading to the biosynthesis and recycling of NAD(P) have recently been described, however, several genes encoding key enzymes are still unknown. In addition, there are only laborious methods for accurately determining the levels of these compounds. We are interested in discovering the genes encoding NAD(P)-related functions as well as in measuring the internal levels of these compounds in response to growth conditions and mutation.
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