RESEARCH ASSOCIATE (postdoc) in DEVELOPMENTAL GENOMICS

The Williams lab at the University of Manchester is looking for an enthusiastic postdoc to join our team studying gene regulatory networks underlying cell fate decisions from the neural plate border. We use chicken embryos as our model and apply single-cell multiomic profiling coupled with in vivo functional perturbations to resolve lineage specific regulatory mechanisms. This information will shed light on how individual cells within the complex environment of the developing embryo activate specific programmes to yield diverse cell types.

Background:

During embryonic development individual cells within the embryo must respond appropriately to a multitude of ‘signals’ to yield distinct cell types. Currently, how immature embryonic cells ‘decide’ their fate is not fully understood. Precise control of cell fate ‘decisions’ is encoded in the genome in the form of multifactorial gene regulatory networks. However, the complexities of such networks are not understood at the mechanistic level.

This problem is exemplified in the neural plate border (NPB). The NPB is a discrete, transient region of the early developing embryo. Cells within the NPB region give rise to neural crest and sensory placode cells as well as some neural and epidermal progenitors. Neural crest cells in turn contribute to a wide range of derivatives in the vertebrate body, including elements of the peripheral nervous system, parts of the heart, pigment cells and craniofacial structures. While placode cells contribute to the cranial sensory systems, nose, ears, and lens. Defects in the ontogeny of neural crest and sensory placodes are associated with one-third of all congenital birth defects. Including a number of neurocristopathies such as CHARGE syndrome and Hirschsprung’s disease, which present with facial abnormalities, growth deficiency, heart defects and defective enteric nervous system innervation, respectively. Furthermore, several cancers are known to arise from neural crest derivatives such as melanoma, neuroblastoma, and glioma.

It is not known how the NPB is endowed with such unique multipotency and, when and how individual NPB cells are directed towards different lineages (i.e., neural crest or placodes). Tackling these questions has proved challenging due to the sparsity and transitory nature of NPB cells. Research in the Williams laboratory combines next-generation single-cell ‘Multiomics’ with innovative developmental biology techniques, to resolve the complex gene regulatory networks underlying cell fate decisions from the emerging NPB, using the chicken embryo as our model system.

Unravelling the intricate gene regulatory networks driving cell fate decisions will help us understand the underlying cause(s) of disease as well as identifying potential targets for therapeutic intervention.

Overall Purpose of the Job

The overall focus of this position is to conduct single-cell multiomics profiling of distinct populations of NPB cells isolated from developing chicken embryos over a time course of early development. Building gene regulatory networks from this data will open up numerous avenues of research, yielding unique opportunities to develop novel approaches to probe the mechanistic intricacies of multipotency and lineage segregation of the NPB.