Jack Flanagan, FCRH ’23, is researching to find a drug for Parkinson’s disease.

According to the student researcher, Parkinson’s is a neurological disease in which the protein alpha-synuclein misfolds, causing proteins to clump together and form an aggregate called a Lewy body. Over time, these aggregates get large enough to disrupt the neurons that form dopamine.

Dopamine is a neurotransmitter associated with pleasure and reward, but it also transmits information to muscle cells.
Flanagan says that when dopamine formation is disrupted, it leads to the muscular issues that are symptoms of Parkinson’s disease.

“The goal of my research is to prevent further damage and possibly reverse damage of the neurons that produce dopamine,” said Flanagan.

In order to accomplish this, Flanagan is working with 27 ligands or molecules and testing their ability to disrupt alpha-synuclein aggregation. According to Flanagan, this involves working with the protein alpha-synuclein as well as smaller molecules that can bind to it to disrupt the aggregation and break apart the clumps.

Flanagan uses computer software to assess how well the ligands bind to the misfolded proteins. This process determines how well the drug would work if made with that certain ligand. He also tests whether his molecules are able to pass through the blood-brain barrier in the skull to make sure the drug would be able to reach the brain.

As of now, Flanagan has narrowed his research down to focus on 15 specific proteins, but he hopes to narrow it down further before he begins testing in the lab because the molecules are expensive.

After this, Flanagan will be able to combine the ligands with the misfolded proteins in the lab to test how well the molecules function.

“Ideally, the software that I use will show a perfect scenario, but all sorts of things can happen in the lab that mess up the bonds,” said Flanagan. Once he finds the best molecules, Flanagan plans to do atomic force microscopy, a type of imaging that will allow him to see the protein bound to the ligand.

Flanagan says that this will give him more information about how strong the bonds are and how well the molecules are disrupting the aggregation. He hopes to finish this stage of research with one or two molecules that successfully disrupt alpha-synuclein.
“A lot of the research people do is building on other people’s research, so hopefully the molecules I find would be a step towards finding a cure for Parkinsons,” said Flanagan.

Flanagan began this research in August 2021 in the research lab of Ipsita Banerjee, Ph.D., a professor and research mentor specializing in biochemistry and its applications in medicine.

Flanagan plans to attend physician assistant school to study psychiatry, so Banerjee suggested a research focus on Parkinson’s since it is a psychiatric disease.

Flanagan will present his research at the Undergraduate Research Symposium in May and hopes to eventually have his research published in a scientific journal.