This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).
Protein production, trafficking and degradation are essential for proper cellular function. Perhaps no cells are more sensitive to imbalances in these tightly coordinated processes than neurons. An important cellular compartment, the endoplasmic reticulum (ER), functions to balance levels of neurotransmitter transporters, receptors, and accessory proteins. Thus, deficits in the capacity of the ER to properly handle intracellular stress, such as misfolded proteins, may dramatically affect the activity or survival of neurons and disrupt homeostasis. The focus of this research is an ER-resident protein called torsinA, a member of a family of proteins that appear to have evolved among all multicellular organisms to act as cellular 'gatekeepers' in the prevention of cellular stress. This research uses the well-studied nematode, Caenorhabditis elegans, as a model system whereby the function of torsinA can be more rapidly discerned. Through a combination of behavioral, genomic, and biochemical experiments for evaluating torsinA activity, this study will advance our understanding of how neurons work to prevent stress and maintain homeostatic balance. C. elegans is ideal for this analysis, as this worm has a defined nervous system, a wealth of genetic tools applicable to detailed mechanistic analyses, and a transparent anatomy that enables changes in ER-associated stress to be quantified in living animals using fluorscent biomarkers. Moreover, the ease by which this organism is manipulated is attractive in terms of providing undergraduate students the opportunity to conduct and achieve significant research goals. Outcomes of this CAREER project include mentoring of graduate students, in addition to engaging underrepresented populations of freshmen students in the discovery process through a combination of classroom and mentored-research experiences through an institutionally-supported program, the Alabama Emerging Scholars, aimed at increasing retention of at risk students by early exposure to research.
