Congratulations to Collin Borcik, postdoctoral researcher in the Rienstra Lab, who was recently awarded a year-long National Institutes of Health Ruth L. Kirschstein Postdoctoral Fellowship (F32).
The funded research is titled, “Structural Biology and Biophysics of Alpha-Synuclein Fibrils by Solid State NMR.” Fibrils arising from the aggregation of alpha-synuclein — a protein found in the human central nervous system — are a diagnostic hallmark in several neurodegenerative diseases, including Parkinson’s Disease and Lewy body dementia.
Earlier this year, Borcik was part of a team that identified the structure of alpha-synuclein fibrils in brain tissue samples from people with Lewy body dementia. His F32 project aims to do the same for brain tissue samples affected by Parkinson’s Disease with dementia. Borcik will then identify ligand binding sites in the alpha-synuclein fibril structures for both diseases. Determining ligand binding sites could assist in diagnoses of Lewy body dementia and Parkinson’s Disease.
“Understanding [fibril] structure is incredibly vital to diagnosis and drug development. We need to know what the individual components do, about their biological function,” Borcik says. “Figuring out the machinery of how a tug here influences a fold here is just really fascinating…And I’d like to contribute to being able to diagnose patients earlier.”
Borcik’s research uses solid state nuclear magnetic resonance to learn more about precise structural characteristics of the fibrils.
“I’m looking at correlations among atoms and working outward to determine the structure instead of looking at the full assembly of the fibrils and refining inwards,” explains Borcik. “This allows us to measure accurate distances between individual atoms, so we can incorporate precise interactions and close contact among atoms into our structural models.”
Borcik and his collaborators are uniquely positioned to carry out this research. UW–Madison is home to the NIH-funded National Magnetic Resonance Facility at Madison (NMRFAM), where Borcik will be using solid state nuclear magnetic resonance to assess the fibril structure of brain samples. NMRFAM is co-directed by Borcik’s postdoctoral advisor, Chad Rienstra, and Katherine Henzler-Wildman. Both Rienstra and Henzler-Wildman are professors in the Department of Biochemistry.
“The facilities here are second to none — we have the institutional knowledge and equipment to investigate emerging questions that may translate to clinical impact. I really appreciate that the research environment here is perfect for me to investigate my own curiosities,” Borcik says.
This work will build on the knowledge and techniques Borcik has been developing in the Rienstra Lab.
“Collin has made excellent progress in his research to understand the detailed molecular structure of alpha-synuclein fibrils,” says Rienstra. “He has developed new sample preparation methods and innovative strategies for obtaining higher quality experimental data using solid state nuclear magnetic resonance. I can’t wait to see the outcomes of this highly significant biomedical research to help us understand how small molecules can be used to diagnose and treat neurodegenerative disease.”
Written by Renata Solan. Photo: Paul Escalante/Department of Biochemistry.