When cells are exposed to environmental stresses, such as heat shock, UV irradiation, or hypoxia, they initiate protective responses to ensure survival. A reversible block of mRNA translation, triggered by phosphorylation of the eukaryotic translation initiation factor elF2a under the action of several stress-activated kinases is one of the most rapid responses. These translationally-stalled mRNAs are sequestered in cytoplasmic structures called stress granules. Triage within stress granules recycles mRNA molecules for translation or directs them for degradation in processing bodies, which contain the mRNA decay machinery. Stress granules themselves contain a collection of molecules that regulate or initiate mRNA translation as well as proteins implicated in RNA remodeling or degradation. Ras-GTPase activating protein (G3BP) is a stress granule endoribonuclease implicated in RNA remodeling or degradation that is also implicated in the regulation of stress granule formation. Recently the PI showed that the dual specificity phosphatase MK-STYX interacts with G3BP and possibly affects stress granule formation. In addition, a second dual specificity phosphatase, PTEN, has been linked to G3BP expression. This linkage between G3BP and phosphatases suggests the intriguing possibility that phosphatases play an important role in the dynamic assembly and/or disassembly of stress granules in response to environmental signals. The concept is novel as stress sensing kinases are known to correlate stress granule formation but there is no known similar function for specific phosphatases. The overall goal of this project is to test the hypothesis that dual specific phosphatases supplement the role of stress sensing kinases in regulating stress granule dynamics by controlling the phosphorylation state of G3BP. The study will clarify the role(s) of dual specific phosphatases as regulators of the cellular stress response.
Broader Impacts This project broadens the curriculum at Hampton University, a HBCU, by integrating science education and basic research in molecular and cellular biosciences. Hampton has a long history as an excellent teaching institution but is now expanding its program to include undergraduate research. However, currently there are limited resources for students to participate in research in the Department of Biological Sciences. Students who obtain research experiences traditionally do so at other schools. However, the goal of this project is to allow Hampton students to continue the traditional off-campus plan for research experiences but to also provide the opportunity for some students to have their first research experience at their home institution. This project will also extend into the Cell Biology teaching laboratory and replace some of the repetitive teaching laboratory experiences with original research associated with the project described here. As an outreach activity students in the Cell Biology course will apply their learning by assisting science teachers at Hampton City Schools in providing laboratory experiences for their students and in assisting students and teachers with the annual science fair. The idea is to introduce middle school and high school students to research early in their training with an ultimate goal of informing students of the research that supports the text and the figures in the textbooks that they use.
