This summer (2014) I fulfilled my 8-week research requirement of the McNair Scholars Program by working as a research assistant in Benjamin Wolozin’s neurodegeneration laboratory in the pharmacology department at Boston University Medical Center. I worked under a Biomolecular Pharmacology/Biomedical Neuroscience Ph.D. candidate named Joon Yvette Boon on a project focused on the neuropathology of Parkinson’s Disease (PD).
The two major proteins involved in PD are α-synuclein and leucine-rich repeat kinase 2 (LRRK2). α-synuclein is the protein that aggregates in Lewy Bodies (LB) which is the hallmark of PD. Mutations in the LRRK2 gene cause autosomal-dominant, late-onset PD.1 Recent studies have shown that α-synuclein has different transcript variants with either a long or short 3’ untranslated region (UTR) and the relative amount of each transcript variant has an implication in PD.2 Recent studies have also demonstrated that LRRK2 plays a key role in transcription.3 My project was to determine if LRRK2 had a transcriptional regulatory role in α-synuclein production and aggregation, as we hypothesized. We found that co-expression of α-synuclein with either long or short 3’UTR and wild-type LRRK2 in HEK293FT cells led to an increase in α-synuclein production in relative to without LRRK2 as measured by florescence level of the GFP-tagged α-synuclein. In addition, we also investigated the effects of mutant variants of LRRK2 (G2019S and R1441C) on α-synuclein expression. Our results demonstrated that α-synuclein with the short 3’UTR is expressed more strongly than α-synuclein with the long 3’UTR .
I am currently a rising junior at Boston College, and while I will not continue working at the Wolozin laboratory in the fall (due to travel time and other extracurriculars) I have gained a lot through this opportunity. As a pre-medical student, I have a new and valuable tool under my belt: bench-work and laboratory experience. As a scientist, I have two new mentors (Joon and Dr. Wolozin) and a more in-depth knowledge about the molecular interactions of proteins within Parkinson’s Disease. As a scholar, my passion for neuroscience has become more prominent than ever, and I leave the lab with more questions than I had coming in.
At the culmination of the eight weeks, I presented our data at a research symposium at Boston College and will be presenting at another symposium there in the spring. Without the stipend from Middlesex− that went to supporting my transportation, meal, and housing costs− this experience simply would not have been possible. Thank you, Middlesex!
1. Ploteghera, Nicoletta, and Laura Civiero. “Neuronal Autophagy, Alpha-Synuclein Clearance, and LRRK2 Regulation: A Lost Equilibrium in Parkinsonian Brain.” Journal of Neuroscience (2012): n. pag. Journal Club. 2012. Web. 7 Aug. 2013.
2. Mclean, JR, PJ Hallett, O. Cooper, M. Stanley, and O. Isacson. “Transcript Expression Levels of Full-length Alpha-synuclein and Its Three Alternatively Spliced Variants in Parkinson’s Disease Brain Regions and in a Transgenic Mouse Model of Alpha-synuclein Overexpression.” Diss. Center for Neuroregeneration Research, McLean Hospital/Harvard Medical School, Harvard University, 2011. Abstract. Molecular and Cellular Neuroscience (2012): n. pag. PubMed. Web. 7 Aug. 2013.
3. Lin, CH, PI Tsai, RM Wu, and CT Chien. “LRRK2 G2019S Mutation Induces Dendrite Degeneration through Mislocalization and Phosphorylation of Tau by Recruiting Autoactivated GSK3ß.” Diss. Nstitute of Molecular Biology, Academia Sinica, 2010. Abstract. Journal of Neuroscience (2010): n. pag. PubMed. Web. 7 Aug. 2013.