How did you spend your summer vacation? The students supported by PDF’s Summer Student Fellowship Program — a group that includes undergraduates and medical students — spend their summers working on PD-related research projects with mentors who have expertise in the field.
Typically, fellowships are offered for 10 weeks with an award of $4,000. Recently, we sat down with former Fellow Will Johnson, M.S., a pharmacology student at Case Western Reserve University, who was awarded funding in 2013, for a project entitled, “Investigating the role of enzyme mediated neuronal protection in Parkinson’s,” to hear about his summer and what he learned about Parkinson’s disease in the process.
Q. When did you first get involved in PD research and what motivated you to do so?
A. Even before I had any direct experience in a lab, I was fascinated by neurodegenerative disease development and the role that genetic mutations play in contributing to disease onset. I first became interested in PD research specifically while working as a research assistant in the lab of Amy Wilson-Delfosse, Ph.D., at Case Western Reserve University in 2010. At the time, my project was focused on generating a “PCR-based assay,” which is a technology used to help us amplify DNA, and more easily identify genetic mutations. My job was to analyze the DNA samples from people with Parkinson’s disease, and to identify genetic mutations including the G2019S mutation in the PD-linked gene LRRK2. It was during this research, as I started to understand the impact of these genetic mutations (specifically the G2019S mutation) in PD development, that I became hooked on PD research.
Q. Can you provide a summary of your PDF-funded project? What was most exciting to you about your findings?
A. Parkinson’s disease is caused by the selective loss of neurons in the brain that control our ability to make voluntary movements, such as walking. It is thought that a process called oxidative stress plays an important role in damaging the type of neurons that produce the neurotransmitter called dopamine (dopaminergic neurons), in turn leading to the development of Parkinson’s disease.
The project that was funded by PDF involved my investigation of the role that an enzyme called Glutaredoxin 1(Grx1) plays in providing protection for these neurons. By analyzing portions of brain tissue obtained from people with PD (and others without PD) who had donated their brains to science, we found that the amount of the enzyme Grx1 was decreased significantly in the dopaminergic neurons in the samples from people with Parkinson’s disease, as compared to those without PD. We then studied an animal model of PD that allowed us to test the effect of Grx1 deficiency more directly, and examine the protective effect of the enzyme in the dopaminergic neurons. Our most exciting finding was showing that Grx1 protects dopaminergic neurons from the adverse effects of several different proteins that increase oxidative stress and induce nerve cell death.
Now, more than a year later, I am investigating the downstream targets of Grx1, trying to identify which proteins directly promote neuronal protection.
Q. How did the funding impact your research and career?
A. The funding from PDF as well as the lessons learned from the experience not only lead to my recent manuscript publication, but also has made me a much more complete scientist.
The grant was invaluable for fostering my PD research at a crucial stage in development of my Ph.D. thesis project. Not only was I able to obtain the necessary reagents for my experiments (substances needed to do the experiment) but also, because of the process of writing the application, I was able to better focus my research, which led to the results that were published in my first-author original research article in the journal Human Molecular Genetics. The experience of writing my first real grant proposal will continue to help me in my future research as an independent scientist. In addition, my success in obtaining funding has given me the confidence to mentor an undergraduate student and encourage him to apply for funding through the PDF. As far as the future, I plan to continue PD research as a postdoctoral fellow. I would like to focus on continuing understanding the role that redox proteins (such as the protein that makes Grx1) play in helping to protect dopamine neurons, with the long-term goal of discovering ways to slow the progression of Parkinson’s disease by finding therapeutics that target these proteins.
Q. Is there anything else you’d like to share with the PD community?
A. As a scientist, I have found collaboration among investigators with complementary expertise is quite valuable. Fundamentally understanding the various aspects of PD is going to require a multidisciplinary approach, and I feel that as a research community we should try and work together with the long-term goal of therapeutic advancement.