**PLEASE NOTE – the deadline for requesting a funding pack from Darwin Trust has now passed and completed funding applications must be submitted to Darwin Trust by 19th January. We can still accept applications for this project from self-funding students.
Neurons are specialized electrically excitable cells that transmit their signals using their two distinctive functional domains, the dendrite and axon. Nociceptive receptor neurons are dedicated peripheral sensory neurons that detect external stimuli such as touch, temperature etc (Hall & Treinin, 2011). These neurons are characterized by their elaborate dendritic arbors that reach out to sense the stimuli. The mechanisms that underlie the elaborate branching of dendrites and their maintenance during the lifetime of an organism is not well understood. Our lab is interested in analysing the role of cytoskeletal proteins in neuronal morphogenesis (Cheerambathur et al., 2019). In this project we will assess the molecular factors responsible for dendritic branching of the the nociceptive receptor neuron, PVD in the small animal model, C. elegans.
It was recently discovered that microtubule binding components of the kinetochore, the mitotic protein machinery that segregates chromosomes have an essential post-mitotic role in dendrite morphogenesis & regeneration (Cheerambathur et al., 2019; Hertzler et al., 2020). Our has identified a function for kinetochore proteins in the branching morphogenesis of PVD, an established model to study dendritic branching and regeneration. What is the function of the kinetochore proteins during dendritic branching and regeneration? In this project we will address this question using a combination of genetic, biochemical and microscopy-based approach.
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.
https://cheerambathurlab.co.uk/
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