Research

Phosphorylation is a common protein modification that regulates activation, deactivation, and/or localization of a target protein. These phosphorylation events occur in signal transduction cascades and many of these cascades are important for basic cellular functions, such as growth, division, and stress response. Protein kinases catalyze the transfer of a phosphate group from ATP to a specific amino acid on a target protein, usually a serine, threonine, or tyrosine. The Alspaugh Laboratory is interested in how phosphorylation plays a role in the ability of the opportunistic human fungal pathogen Cryptococcus neoformans (Cn) to grow and divide under stress conditions, such as extremes of pH and hypoxia.

Cn is responsible for >100,000 deaths annually in primarily immunocompromised patients. During infection of a human host, Cn must adapt to host-derived stress conditions which include shift from acidic to alkaline pH and oxygen starvation. Therefore, I hypothesize that kinases are preferentially phosphorylating proteins under alkaline and/or hypoxic stress and these modifications are important for stress response and adaptation. To test this I screened through a library of 129 kinase mutants and identified 39 kinases being required for growth under alklaine stress. Of these 39 kinases, I was particullary interested Casein kinase 1 (Cck1) because prior work demonstrated that this kinase was important for Cn pathogenesis. Cck1 is a conserved serine/threonine protein kinase that is found in eukaryotic organisms from yeast to humans and interacts with proteins in many different signal transduction pathways. Prior work in Cn established that Cck1 is involved in a wide range of cellular functions across multiple signaling pathways. However, these study did not identify the proteins Cck1 phosphorylates, nor did it assess alkaline pH and hypoxic stress. Therefore, my research is focused on elucidating the role of in Cn Cck1 involvement in cell function and signal transduction pathways under alkaline and hypoxic stress conditions that contribute to pathogenesis.