Specifying neural crest cell from ‘scratch’
Supervisor: Prof Tatjana Sauka-Spengler
Neural crest (NC) is a unique multipotent embryonic cell population that differentiates into a plethora of diverse cell types, giving rise to structures as different as neurons and glia of peripheral nervous system, bone, cartilage and connective tissue elements of craniofacial skeleton and body’s pigmentation. Defects in neural crest patterning are some of the most common causes of birth anomalies, accounting for up to one-third of all congenital birth defects. Due to the unique multipotency, developmental plasticity and extensive migratory potential of neural crest cells, there is today broad interest in using their regenerative capacity in stem cell-based therapeutics.
By systematic genome-wide profiling of the neural crest regulatory landscape in two model organisms, zebrafish and chicken, our laboratory has, over the past few years, gained an unprecedented systems level insight into the complex gene regulatory programmes that underlie early steps of neural crest formation. With the regulatory picture obtained directly from developing embryos, we started to unravel the chromatin dynamics events at the regulatory loci, characterising the structure of the topologically associating domains of neural crest regulators and probe the cis-regulatory elements that co-ordinate neural crest programme. This unique breadth of information now allows us to explore and utilise gene regulatory interactions uncovered to model minimal neural crest specification programme and develop protocols for directed specification of neural crest derivatives from stem cells.
At this point we are engaging in multiple lines of investigation of neural crest gene regulatory network. For example, we offer opportunities to study complex mechanisms such as multiple enhancer convergence in super enhancer-like clusters, to decipher the events of commitment to neural crest fates at a single cell level from the chromatin/gene regulatory interaction standpoint, or to target and activate critical neural crest circuits endogenously in human embryonic stem cells using novel epigenome engineering (EGE) approaches (Crispr/Cas9 effector technology), already existing in the lab. We are looking for an excellent, motivated and creative candidate to become a part of our dynamic and ambitious team. The successful candidate will receive first hand training in cutting edge, state-of-the-art genome-wide profiling and epigenome engineering technologies, as well as in developmental genomics and computational biology, to be able to successfully tackle the chromatin changes or activate regulatory elements that prime and drive neural crest programme during embryonic development. The candidate will be allowed to influence and freely shape his/her project, while at the same time being carefully advised on feasibility and potential pitfalls of the approaches. It is our aim to foster creativity, novelty and excellent science, provide multifaceted training while answering questions at the cutting edge of our field. The candidate will be embedded within a dynamic group of researchers that employ genetic and system biology approaches to study gene regulatory circuitry in the various contexts of development and disease and will have ample opportunities to grow in spheres of genomics and quantitative biology, as well as to develop collaborations with modelling and stem cell biology groups.
For further information, please contact Prof Tatjana Sauka-Spengler