About the Project
Microtubule functional diversity in neuronal cells requires the activity of several microtubule regulators, and mutations in these proteins are linked to human neurodevelopmental disorders (Kapitein and Hoogenraad, 2015). Despite advances in our molecular understanding of microtubule regulators, the mechanisms by which they contribute to the structure and function of a developing neuron are largely unknown. It was recently discovered that microtubule binding components of the kinetochore, the mitotic protein machinery that segregates chromosomes are essential for neuronal circuit formation (Cheerambathur et al., 2019; Zhao et al., 2019). What is the function of the kinetochore microtubule machinery in a developing neuron? This project will focus on understanding this novel post-mitotic neuronal function of kinetochores in C. elegans and mammalian cell culture systems.
Overall the student will learn state-of-the-art in vivo high-resolution live cell microscopy, biochemistry, genetics (e.g. CRISPR based genome edits) and molecular biology techniques. The student will engineer and develop visualization tools (e.g. microtubule, membrane and neuronal cell specific markers) to assess the morphological and cytoskeletal changes associated with neuronal development and wiring of the nervous system. These tools will then be used in conjunction with genetic approaches (e.g. loss of function alleles & knockouts) to determine the functions of kinetochore proteins in neuron. The student will also be trained various image analysis tools (e.g. Image J). Taken together, the student will develop experience in quantitative cell biology using the latest genetic and imaging tools to tackle questions related to neuronal development.
The School of Biological Sciences is committed to Equality & Diversity: https://www.ed.ac.uk/biology/equality-and-diversity
If you would like us to consider you for one of our scholarships you must apply by 6 January 2021 at the latest.
Kapitein, L.C., and Hoogenraad, C.C. (2015). Building the Neuronal Microtubule Cytoskeleton. Neuron 87, 492–506.
Zhao, G., Oztan, A., Ye, Y., and Schwarz, T.L. (2019). Kinetochore Proteins Have a Post-Mitotic Function in Neurodevelopment. Dev. Cell 48, 873–882.e874
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