“Parkinson’s Disease: Mapping the Receptor JHA1’s Functional Domain In the Endocytosis of α-Synuclein PFF”
Parkinson’s disease and Parkinsonism are caused by the neurodegeneration of the motor neurons in the substantia nigra. Misfolded strains of the protein α-synuclien (α-syn), a protein abundant in neurons, have been found to lead to toxic aggregations in neuronal cells known as Lewy Bodies. In this study the most toxic fibrillar form of misfolded α-syn, pre-formed fibrils (α-syn-PFF), were used to elucidate the functional domain of a nascent transmembrane receptor, JHA1, in its role as a mediator of α-syn-PFF endocytosis. Previous study has shown that fibrillar α-syn behaves like prions; it is transmitted from cell to cell and misfolds healthy, endogenous α-syn in the process. Using confocal microscopy analysis of different domain deletions, it was found that of the four functional domains of the transmembrane protein, only the first domain was needed to observe increased endocytosis of α-syn-PFF. In that domain’s five subdomains, only the second and third were functional in the endocytosis of PFF. It is hoped that this discovery will aid in formulating targeted therapies in Parkinson’s disease.
Can you explain your research project in everyday terms?
My research contributed to a large future paper that describes some previously undiscovered aspects of proteins that have a role in Parkinson’s disease pathology. I specifically worked on collecting qualitative and quantitative data on the endocytosis (when a cell takes something into itself) of a misfolded strain of α-synuclien protein, an important protein in neurons, which can accumulate to form Lewy Bodies. These Lewy Bodies are a hallmark of Parkinson’s disease and other neurodegenerative diagnoses such as Lewy Body Dementia. The exciting crux of the paper is that there seems to be a receptor that binds these misfolded proteins preferentially. Inhibition of this receptor may have tremendous benefit in the treatment of Parkinson’s disease.
Who is your mentor for this work?
My mentor was Dr. Xiaobo Mao, working in the Neuro-Institute for Cell Engineering on the Johns Hopkins Medical research campus.
How long will it take you to get results on this project?
The overall project is maybe over a year in the making. I was able to get results in my small contribution, observing neuron cultures with confocal microscopy, in about month but a great deal of preliminary work had been done by my mentor.
Have you presented your research to others? Where? Who was in the audience? How did it go?
I presented a poster in Johns Hopkins’ annual summer undergraduate research symposium and gave a presentation to the Hopkins Inistitute of NanoBiotechnology. The poster was presented on the Hopkins Medical School campus to Hopkins researchers, a few medical doctors and other students. The oral presentation was to the primary investigators, mentors and students involved in the Institute of NanoBiotechnology. The poster session went very smoothly. The oral presentation could have been slightly more polished (counterintuitively, it takes preparation to act natural), but I really enjoyed it. I love presenting information to people.
Was there any difference from your previous research? Was this a continuation?
This research had very little to do with my previous summer’s research. Basic wetlab skills were the same, but last year I focused on learning different nano-science techniques in several chemistry labs while this year I focused on a specific project in one neuroscience lab for the duration of my internship. Even so I could think of some ways in which future research could combine some of the ideas I learned in each internship to study possible Parkinson’s disease therapies.
What have you learned about yourself and your career/education goals through research?
I’ve learned a great deal about both good and bad aspects of my temperament. I have a tendency to work very hard, but I really need to work on planning. I think this research has opened me up to some new directions in my career goals and confirmed my interest in biomedical engineering. Research in the hard sciences is really “doing God’s work,” but I’m ultimately interested in translation: delivering treatments suggested by hard science discoveries to patients faster using engineering principles.
Did you make use of any of the undergraduate research web pages when you were trying to get started in research? What was helpful to you?
Yes, I’ve pretty much read through all of the Office of Undergraduate Education research related pages. Before making my poster, the guidelines on making a poster were very useful. (Incidentally, it was written by one of the professors that graciously wrote me a recommendation!)
Has the Career Center helped you? How?
Yes, Ms. Kidwell-Slak and others helped me fine tune my resume before applying. In general, the job application advice given by the Career Center is applicable to research, but I also participated in the PRAC program this summer which provided me with some ideas about communication that I found valuable.
What advice would you give to a student newly interested in research about how to get started?
I think research requires a lot of focus, so apply in labs or to opportunities that actually interest you. This will also make your application stronger. Take the time to understand the some of the research done by the labs or REUs you are interested in and formulate intelligent questions about the research that you may be interested in exploring or just knowing more about. Most researchers do very narrow, specific work. Being familiar and interested in that work is almost like fostering a personal connection with them. As far as applying to REU type opportunities, the Office of Undergraduate Education is your best friend at UMBC.