Tonya Zeczycki, PhD APDA Research & Impact Research Investigators Tonya Zeczycki, PhD Name of Institution: Brody School of Medicine at East Carolina University, Greenville, NC Project Title: Identifying the Consequences of Transglutaminase 2 (TG2)-Mediated Posttranslational Modifications on Alpha-Synuclein Oligomerization Investigator: Tonya Zeczycki, PhD Dr. Zeczycki is an Assistant Professor in the Department of Biochemistry and Molecular Biology at the Brody School of Medicine at East Carolina University. Dr. Zeczycki’s research is focused on investigating how post-translational modifications of α-synuclein by transglutaminase 2 contributes to protein aggregation in the brain. Her hypothesis is that specific modifications result in aggregate competent and incompetent conformations of a-synuclein. Research Objectives and Relevance to Diagnosis/Treatment of PD: Transglutaminase 2 mediated posttranslational modifications of α-synuclein can both facilitate and inhibit toxic α-synuclein oligomer formation by stabilizing specific aggregate-competent or resistant conformations of α-synuclein The objective of this proposal is to identify the differential effects Transglutaminase 2-mediated modifications have on the ability of α-synuclein to adopt conformations that are either aggregate-competent (i.e. forms oligomers) or aggregate-resistant (i.e. does not form oligomers). A hallmark of Parkinson’s disease (PD) is the formation of protein oligomers and fibrils in the brain that are comprised almost entirely of the intrinsically disordered protein, α-synuclein. There are numerous cellular, genetic and environmental factors which promote a-synuclein oligomerization, including the posttranslational modification of α-synuclein by transglutaminase 2. Little, however, is known as to how these specific posttranslational modifications facilitate the formation of α-synuclein oligomers.