*EASTBIO* Investigating the role of chromosome segregation machinery during neuronal morphogenesis

A fundamental event in neuronal morphogenesis is the establishment of neurites that develop into morphologically and functionally distinct domains of a neuron, the dendrite and axon. It is well known that this process involves dynamic remodelling of the microtubule cytoskeleton whereby a radial microtubule array in a neuronal precursor reshapes, acquiring uniform polarity in axons and mixed polarity in dendrites. However, the precise function of the microtubule cytoskeleton as well as the molecular mechanism behind neurite establishment is poorly understood. Several classes of microtubule-associated proteins are known to function during neuronal development and many are mutated in neurodevelopmental disorders. Understanding how the function of the different microtubule regulators is spatially and temporally coupled to the neuronal differentiation program is imperative to determine how developing neurons generate the distinct local subpopulations of microtubule arrays.
Besides the known microtubule regulators, we recently discovered that components of the protein machinery that segregates chromosomes are essential for proper neurite extension in developing neurons as well. The goal of this project is to understand how chromosome segregation machinery components are spatially and temporally regulated during neurite differentiation in C. elegans embryos. To tackle this question, the project will draw on the expertise of the Cheerambathur Lab in mechanistic analysis of chromosome segregation machinery components and the Storey Lab in regulation of neuronal differentiation.
The student will engineer and develop visualization tools (e.g. cytoskeletal, membrane and neuronal cell specific markers) to assess the morphological and cytoskeletal changes associated with neurite extension. These tools will then be used in conjunction with genetic approaches (e.g. loss of function alleles) to determine the functions of chromosome segregation machinery components in neurite extension. The student will also be trained state-of-the-art in vivo high-resolution microscopy, image analysis tools (e.g. Image J), genetic and molecular biology techniques. 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. Additionally, this collaborative effort will allow the student to work in labs with complementing expertise and access the state-of-the-art research and training environment offered by the two institutions, the Wellcome Centre for Cell Biology in Edinburgh and School of Life Sciences in Dundee.