Elucidating the function of RNA binding proteins during development and maintenance of neural connections

The University of Bath is inviting applications for the following PhD project based in the Department of Biology & Biochemistry under the supervision of Dr Nikolas Nikolaou.

Neural circuit function and ultimately animal behaviour depend on the precise formation of synaptic connections in the brain. Deviations in the way neurons connect with one another can lead to neurodevelopmental disorders, such as autism, schizophrenia and bipolar disorder. The ability of neurons to form connections in the brain relies on the correct repertoire of proteins present in pre- and post-synaptic partners, which is the direct result of differential gene expression in these cells. RNA metabolism is a major mechanism regulating neuronal development and is carried out by an army of RNA-binding proteins. Mutations in genes encoding such factors are often associated with neurological conditions, demonstrating the important roles RNA-binding proteins have for nervous system function. Spliceosomal proteins consist a major class of RNA-binding proteins and they drive constant and alternative splicing of pre-mRNAs, processes known to take place in the nucleus of all eukaryotic cells. There is an increasing amount of evidence indicating the presence of spliceosomal proteins in neurites; however, their cytoplasmic roles are not yet understood. Key questions concern:

1. What are the non-nuclear functions of splicing factors during development and maintenance of neural connections?
2. What are the immediate transcriptomic changes associated with the non-nuclear function of splicing proteins in neurons?
3. With what other proteins do splicing factors interact with in neurites?
4. How does the cytoplasmic pool of splicing factors influence the function of neural circuits, i.e. synapse formation, neuronal activity, animal behaviour?
5. How do changes in neuronal excitability influence RNA processing in neurites?

Key opportunities exist for an ambitious individual with background in neuroscience, cell/developmental biology and/or genetics. You will join an ambitious and experienced new team utilising the zebrafish model to explore one or more of these questions. We are using the full range of approaches available in this model system, which provides excellent opportunities for genetic manipulation and imaging. Such approaches include single cell transcriptional profiling, CRISPR/cas9 and transgenesis techniques, whole-mount immunofluorescence, together with structural and functional imaging techniques to access neuronal cell behaviour and function.

Candidate requirements:

Applicants should hold, or expect to receive, a First Class or high Upper Second Class UK Honours degree (or the equivalent qualification gained outside the UK) in a relevant subject. A master’s level qualification would also be advantageous. Non-UK applicants must meet our English language entry requirement http://www.bath.ac.uk/study/pg/apply/english-language/index.html.

Applications:

Informal enquiries are welcomed and should be addressed to Dr Nikolas Nikolaou.

Formal applications should be made via the University of Bath’s online application form:
https://samis.bath.ac.uk/urd/sits.urd/run/siw_ipp_lgn.login?process=siw_ipp_app&code1=RDUBB-FP02&code2=0014

Please ensure that you quote the supervisor’s name and project title in the ‘Your research interests’ section.

More information about applying for a PhD at Bath may be found here:
http://www.bath.ac.uk/guides/how-to-apply-for-doctoral-study/

Anticipated start date: 28 September 2020.