Graduate Alumni Research Award, Pinar Gurel
PhD student in the Molecular and Cellular Biology (MCB) Program, Pinar Gurel, describes her work on proteins associated with the cytoskeleton as part of the Graduate Forum series on Graduate Alumni Research Award recipients.
Winning the Graduate Alumni Research Award has made an important difference in my research this year. My work examining the molecular mechanisms of cellular structure requires special equipment that would have been difficult for me to access without the support of this award.
Just like the human skeleton is responsible for giving our body shape and allowing us to move, in each of our cells the cellular skeleton—or cytoskeleton—functions to ensure proper cellular shape and motility. Actin, one component of the cytoskeleton, is crucial for a variety of cellular processes such as migration, division, and organelle shape maintenance.
Several factors regulate the assembly, maintenance, organization, and disassembly of the actin cytoskeleton, and in our lab, we are especially interested in one such factor called INF2. Mutations in INF2 can lead to the kidney disease Focal and Segmental Glomerulosclerosis (FSGS) or the neurological disease Charcot-Marie-Tooth Disease (CMTD), so we are particularly interested in understanding the mechanism of its regulation and action on the actin cytoskeleton.
INF2 functions as an actin assembly factor, but uniquely, it can also disassemble actin filaments through a mechanism involving filament severing. My research aims to clarify the molecular mechanism of INF2-mediated actin severing. I have been using purified, fluorescently labeled INF2 and actin to visualize severing in vitro using a technique called TIRF (Total Internal Reflection Fluorescence) microscopy. This visualization method is ideal for monitoring the process in real-time. However, I am faced with a huge obstacle preventing my progress on this project: the availability of a TIRF microscope with sufficient specifications to capture filament severing by INF2.
Thanks to the Graduate Alumni Research Award, I have been able to afford travel to labs in Woods Hole, Massachusetts and to Brandeis University in Waltham, Massachusetts that are equipped with TIRF microscopes. By using a device capable of acquiring rapid images in dual-color, I have discovered that INF2 can bind to filament sides by wrapping around the filament, and then can sever at the location where it is bound.
This novel finding provides insight into the role of INF2 in manipulating the actin cytoskeleton in cells. Furthermore, clarifying this biochemical mechanism contributes to our understanding of the pathology of INF2 in diseases such as FSGS and CMTD.
by Pinar Gurel