The beauty of basic research is that sometimes, when you’re not looking for it, you make a discovery that answers a critical question in an entirely new or different field.
That’s what happened to Dr. Geoffrey Hesketh. Dr. Hesketh, a cell biologist, was investigating how proteins move around in cells to arrive at their surface in the correct order required to do their jobs. He was concentrating on the Retromer proteins, a group of proteins that work together to pick transport proteins from their starting point to the correct spots that allow them to send and receive communications signals.
Other researchers had already figured out that damaged forms of one particular protein in the group – a protein called VPS35 – lead to Parkinson’s disease. Dr. Hesketh’s work revealed that nine other genes associated with Parkinson’s disease are also part of the Retromer group. That discovery points to this group of proteins as being critical players in the cause of Parkinson’s disease.
Now Dr. Hesketh, who has switched the focus of his project to Parkinson’s, uses a technique called mass spectrometry to screen all the proteins in the Retromer group. He wants to identify all the proteins they communicate with, because they could also be implicated in Parkinson’s disease. Dr. Hesketh was recently awarded a two-year, $100,000 Basic Research Fellowship from the Parkinson Canada Research Program to pursue this research.
The next step for researchers is to figure out how and why, when things go wrong in the Retromer group, Parkinson’s disease results. One theory is that any defect in the Retromer pathway results in fewer proteins getting to the right spots on the surface of brain cells. That could disrupt communication among the cells. Cells that produce dopamine – the chemical in the brain that affects movement – could be more susceptible to this disruption.
“Or it just could be that after losing their connections with the neighbouring cells, these cells (with damaged Retromer proteins) just shrivel up and die,” Dr. Hesketh says. « Knowing exactly what goes wrong at the cellular level is critical for the design of any future drug to treat Parkinson’s, » he says.
He is passionate about the need for basic research and its unintended consequences, rather than only funding research with direct medical or industrial applications.
“You can sometimes learn much more about a disease process when you don’t even know you are studying that disease in the first place,” he says. “I think I’m a good example of that.”
Dr. Hesketh was invited to attend a symposium of Parkinson Canada’s Scientific Advisory Board last month, when the members presented their research to one another. You can watch our interview with Dr. Hesketh, recorded after this meeting, below. You can also read about other researchers funded by the Parkinson Canada Research Program.