Biochemistry / Psychology / Math
Project title: Mechanism of neurotoxic α-synuclein oxidation by dopamine in Parkinson’s disease
Mentor: Kathryn Matera
During fall 2013 I completed two more hours of work on my Lumen project bringing me just one hour away from completion. In order to add more confidence to aggregation data obtained in previous semesters, an attempt was made to replicate thioflavin T assay results by measuring multiple time points rather than one end point. Attempts to run time lapse trials were not successful, but through my experiments I learned a great deal about the nuances of thioflavin T assays which will be great for me to pass on to the next researcher that comes through Dr. Matera’s lab. Moving forward, I picked up on an investigation that I began last spring. I have aggregation data that suggests DL- norepinephrine prevents the formation of large α-synuclein inclusions like the ones found in Parkinson’s disease, so the next question was to see what is happening to the α-synuclein monomers if they are not forming large aggregates. To do this I purchased a silver staining kit and ran a protein gel of samples that I had let aggregate for 48 hours either in the presence of excess water or in the presence of DL-norepinephrine. The resulting stained gel showed bands at predicted molecular weights for low-weight oligomers made of up to six protein units which confirmed that the silver staining procedure was going to work. I ran the same experiment again, except I only incubated my samples for 24 hours. After running another gel, bands representing small oligomers could be seen clearly in the samples containing DL-norepinephrine but not in either of the controls. The presence of oligomer bands only in the sample containing the dopamine derivative signifies that DL-norepinephrine accelerates the formation of oligomers. This data gives me enough evidence to put together some idea of what could be happening in a biological system which is exciting since my time at Elon is almost over.
The accumulation of data and experiments over the past year and a half has led to the formulation of a new theoretical mechanism that could contribute the pathology of Parkinson’s disease. Beginning in the affected dopaminergic cells, NMR studies have suggested that ROS species, such as hydrogen peroxide, have the potential to circumvent the normal oxidation pathway of dopamine and lead to the formation of DL-norepinephrine. Using a thioflavin T analysis of α-synuclein aggregation, DL-norepinephrine was then shown to prevent the formation of large, insoluble Lewy bodies. Currently, it has been shown that DL-norepinephrine not only prevents the formation of insoluble aggregates, but it also accelerates the formation of the potentially toxic soluble oligomer form of the α-synuclein protein. Oligomers may then move through the cell, opening up pores in cell membranes that lead to neuronal death. Through this pathway it is possible to trace an initial insult on the brain to the characteristic symptoms of Parkinson’s disease.
Additionally, in the fall I presented my research in Atlanta at the Southeastern Regional Meeting of the American Chemical Society and had an abstract accepted for presentation at this year’s National Conference on Undergraduate Research in April.
Dr. Ann J. Cahill
Professor of Philosophy
Spence Pavilion 111
2340 Campus Box
Elon, NC 27244
Phone: (336) 278-5703
Omolayo Ojo is competing for a highly competitive national fellowship awarded each year to those with goals of working in public service or government. Winners will be announced in April.
Victoria Del Gaizo Moore, assistant professor of chemistry, and Karl Sienerth, professor of chemistry, along with Mary Bedard '12 (Biochemistry) and Kelly Giffear '12 (Biochemistry) had a research article accepted to the journal Biophysical Chemistry.
The political science and international studies double major is a Lumen Scholar studying the evolution of LGBT rights in parts of Europe.
Elon University students in a Winter Term "Burst the Bubble" course welcomed local children and their parents to campus in late January for activities that exposed youth to the academic and career possibilities of programming and software design.
Elon University senior Leigh Iler developed strategies for a middle school tutoring program as she studied an emerging technique for deciding whether students require special education.