Molecular genetics of neural crest cell fate choice

Neural crest cells (NCCs) are a key example of a stem cell type that has been widely studied in vivo and in vitro. NCCs are remarkable for the diversity of distinct cell-types that they form, including multiple neuronal, glial, pigment and skeletogenic fates. Consequently, these stem cells are crucial for normal development of all vertebrates. Conversely, many human congenital defects involve abnormalities of NCC development, including Hirschsprung disease, Waardenburg syndromes and piebaldism. Understanding how NCCs choose between alternative fates will have implications for these disease conditions, as well as revealing basic mechnisms of stem cell biology.

Work in mouse and zebrafish has been critical to identifying some of the key genetic players in specification of these individual fates from multipotent NCCs, including transcription factors of the Sox, Tfe, Pax, Tfap and other families. However, recent work shows that we still have only a superficial understanding of these mechanisms. Key questions concern:

1) What are the transcriptional targets of the important transcription factors?
2) How do these factors form a gene regulatory network selecting individual fates?
3) What is the identity of factors acting in specified cells to repress alternative fates?
4) When and where does fate specification occur?
5) What intermediate cell types are formed as part of the process of selection of individual fate choices?
6) How are these intermediate cell-types specified genetically?

Key opportunities exist for ambitious individuals with at least a high 2.i in a relevant degree; backgrounds in bioinformatics, biological mathematics, genetics and/or developmental biology will all be relevant. You will join a multidisciplinary team that has more than 25 years’ experience utilising the zebrafish model to explore one or more of these questions (see References). 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 whole-mount and RNAscope in situ hybridisation, immunofluorescence, single cell transcriptional profiling, CRISPR-Cas9 mutagenesis and small molecule manipulation of signalling pathways, as well as integrating mathematical modelling with biological experimentation to objectively assess our understanding.

The University of Bath and our Department are committed to equality of opportunity. We particularly encourage applications from under-represented groups, including women.