Research Department: Department of Molecular Biology Graduation Date: May 2019
Abstract: Traumatic brain injury (TBI) results in mitochondrial stress and excess production of reactive oxygen species (ROS), which are byproducts of oxidative phosphorylation that are known to cause secondary damage to cerebral tissue. Manipulation of mitochondria electron transport chain efficiency by increasing proton leakage across the mitochondria membrane can decrease ROS production. Current models to reduce ROS concentration have focused on increasing activity of antioxidants, such as ROS scavengers; however, these results did not translate to clinical trials. Here, usingC. elegans, we sought to reduce ROS concentration by limiting its production through RNAi knockdown of cytochrome c oxidase (cco-1), the fourth protein complex in the electron transport chain that transfers electrons to oxygen. It’s previously been shown that cco-1 knockdown can have beneficial effects in C. elegans, such as increased lifespan. Here we show that decreasing ETC efficiency through cco-1 knockdown leads to neuroprotective effects and decreased ROS production following injury.
What does research mean to you? In spring 2018, I conducted research full-time in Dr. Peter Douglas’s molecular biology lab as part of the Green Fellowship. My research experience has helped me to discover an interest for questioning and experimentation. The result from my first assay was astonishing: it appeared that electron transport chain uncoupling could have potential neuroprotective effects following neurotrauma. This was an unexpected finding, and the obvious question that I wanted to ask next was “How? Through what mechanism does this happen?” I formed a hypothesis and designed subsequent assays to resolve these questions. In research, the story naturally unfolds itself. All I need to do is keep asking “what’s next?” The most valuable lesson that I have gained from research is to always be intellectually curious. Tell us about your journey. For 1.5 years, I conducted research with Dr. Christa McIntyre’s lab, studying the use of cuff electrodes for vagus nerve stimulation (VNS) as a potential treatment adjunct to post traumatic stress disorder. My project in the lab specifically investigated the anxiolytic attenuation of VNS effects through a drug called methylscopolamine. My research training in the lab led to my interest in biomedical research, and I began working with Dr. Peter Douglas in January 2018.
Advice for Future Green Fellows
Be intellectually inquisitive. Read scientific papers. Go to WIPs (works in progress talks) and ask questions. Ask your PI’s for feedback and assistance. Keep a careful log of all your assays in a scientific notebook.
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