Identification and characterisation of conserved protein families involved in ciliary function and diseases

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DTP overview:This MRC-funded doctoral training partnership (DTP) brings together cutting-edge molecular and analytical sciences with innovative computational approaches in data analysis to enable students to address hypothesis-led biomedical research questions. This is a 4-year programme whose first year involves a series of taught modules and two laboratory-based research projects that lead to an MSc in Interdisciplinary Biomedical Research. The first two terms consist of a selection of taught modules that allow students to gain a solid grounding in multidisciplinary science. Students also attend a series of masterclasses led by academic and industry experts in areas of molecular, cellular and tissue dynamics, microbiology and infection, applied biomedical technologies and artificial intelligence and data science. During the third and summer terms students conduct two eleven-week research projects in labs of their choice. Project overview: Cilia (also termed flagella) are cellular protrusions with diverse functions. Motile cilia "beat" to allow cellular movement and movement of fluids across tissue surfaces, and immotile cilia act as the cell's sensory antennae and have key roles during animal development. A plethora of human syndromes (collectively called "ciliopathies") are caused by defective cilia. Cilia are evolutionarily ancient, and the main structural features were present in primordial cells more than 1.5 billion years ago.African trypanosomes are an excellent system for ciliary studies. Trypanosomes are easy to culture with unrivalled genetic tools and database resources. Moreover, ciliary function is essential for their virulence and transmission and their ability to cause human African Sleeping Sickness.This project will use evolutionary analyses to discover new, uncharacterised ciliary protein families. Members of these families will be investigated in two very different model systems to understand them better: trypanosomes (single celled and highly tractable) and cultured human cells (human genetic disease relevance).This project will provide high quality training in data science (programming and working with large datasets) and experimental biology (molecular genetics and biochemistry). This intersects with the MRC strategic priority of Interdisciplinary skills as it is at the interface of computational and molecular-cell biology.