2020 |
Chapman, Dail |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
The Architecture of the Membrane Periodic Skeleton (Mps) and Its Role in Mechanical Neuroprotection
As we improve technologies and extend preventative health care, our life expectancy as humans continues to grow. We live longer than before, which in turn gives rise to diseases we haven?t before experienced. Neurodegenerative diseases are among such diseases, and in order to develop effective therapies to combat these diseases, we must improve our understanding of how neurons function and the mechanisms that they have to protect themselves. The Goodman lab at Stanford University is well positioned to study this system due to decades of expertise studying the neuronal cytoskeleton in peripheral neurons. I will greatly contribute to this effort by bringing experimental capabilities and conceptual expertise as I?ve focused my research efforts on the cytoskeleton. Particularly, I aim to understand how peripheral neurons withstand great mechanical stress on their own, without bone or other dense tissue protection. In order to study this, I will use the widely applied model organism, C. elegans. This multicellular, eukaryotic worm model organism is ideal for my studies because it has a completely mapped nervous system, simple neuron morphology, translucent bodies, and tractable genome. In particular, I will focus on their touch receptor neurons because this class of neurons is prone to mechanical stress, is very similar to human touch receptor neurons, and is amenable to testing neuronal function with simple in vivo behavioral assays. While work from my lab has shown that the cytoskeletal protein spectrin is important for touch receptor neuron stability and function, we do not know how spectrin works in concert with other proteins to create an intricate stabilizing membrane periodic skeleton that we suggest is vital to maintain the neuron?s structure in the face of mechanical stress. Through this work, I will apply interdisciplinary approaches to determine which cytoskeletal proteins are necessary for neuron stability and function (Aim 1), resolve the structural details of the membrane periodic skeleton (Aim 2), and determine if this system is conserved among other peripheral neurons (Aim 3). The long-term goals of this research will elucidate how neurons combat mechanical stress. This work will contribute to this goal by detailing the neuronal cytoskeletal network in C. elegans touch receptor neurons. I anticipate this work will directly inform future therapeutic developments targeting human neurodegenerative diseases.
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0.954 |