Ph.D., Biochemistry, Purdue University, 1985
B.S., Chemistry, Illinois Institute of Technology, 1978
A key event in the development of living organisms was the development of mechanisms for sensing and responding to external signals. The ability to detect nutrients and evade toxins conferred on simple unicellular organisms a massive advantage over their deaf and blind peers. The ability of cells to communicate with one another and coordinate their activities was a necessary prerequisite to the emergence of more complex organisms made up of multiple, functionally specialized cells – such as Homo sapiens. Our laboratory is using the members of the third domain of life, the Archaea, as “living fossils” for the dissecting the development of protein phosphorylation-dephosphorylation, a versatile molecular regulatory mechanism that represents one of the cornerstone building blocks for the prolific signal transduction networks in higher animals. By using phylogenetic diversity to look back over evolutionary time, we hope to map out the core of our own highly sophisticated sensor response networks. Reconstructing the development of these networks will provide useful insights into the principlaes upon which they function.
Currently, we are in the midst of identifying the protein kinases and protein phosphatases responsible for the control of protein function by phosphorylation and dephosphorylation in Sulfolobus solfataricus, an extreme acidothermophile that grows in volcanic hot springs such as those found in Yellowstone National Park. Examination of the organisms genome sequence revealed ten open reading frames encoding for plausible eukaryote-like protein kinases and two for protein phosphatases. We have expressed and characterized several of these.
Currently, we are concentrating on a set of three protein kinases that resemble the family of protein kinases in eukaryotes that shut down protein synthesis in response to nutrient deficiency, viral infection, and other stresses. The first of these, dubbed SsoPK4, phosphorylates translational initiation factor 1A, a key component in the formation of the translational initiation complex that forms as the first step in synthesizing a polypeptide from its mRNA. Interestingly, SsoPK4 is activated by oxidized Coenzyme A, a compound that accumulates in S. solfataricus when it is subject to oxidative stresses. The oxidized form of Coenzyme A is a dimer linked by an S-S bond. Analyses to date indicate that the dimeric nature of the compound is key to activation, as it serves as a bridge between two molecules of SsoPK4. When brought into close proximity to one another, each unit phosphorylates and activates the other. Current work aims to determine what signals control the other two homologues of SsoPK4 in S. solfataricus.
As chair of the education and professional development committee of the American Society for Biochemistry and Molecular Biology [ASBMB], I am a participant in national efforts by the ASBMB to improve instruction in Biochemistry, Molecular Biology and other scientific disciplines in our colleges and universities as well as in K-12 schools; and in disseminating information about career options available to students interested in Biochemistry as a profession.