(Bicentenary) Using single-cell Multiomics to unravel cell fate decisions during early embryo development The University of Manchester in United Kingdom

The early developing embryo is a complex dynamic environment. During development, individual cells within the embryo must respond appropriately to a multitude of ‘signals’ to yield distinct cell types, e.g., neurons, muscle cells and bone to form our body’s organs and structures e.g., brain, heart, and skeleton. Currently, how immature embryonic cells ‘decide’ their fate is not fully understood. Precise control of such developmental processes 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 are multipotent, meaning they give rise to a number of different cell types and tissues. Specifically, NPB cells generate neural crest and sensory placode cells. 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 the craniofacial skeleton. While placode cells form the cranial sensory structures, nose, ears, and lens. Defects in the development of the neural crest and sensory placodes are associated with one-third of all congenital birth defects including cleft palate and other facial abnormalities. As well as a number of syndromes including CHARGE syndrome and Kabuki syndrome, both of which present with facial abnormalities, growth deficiency, heart defects together with hearing problems and intellectual disabilities. Furthermore, a number of cancers are known to arise from neural crest derived structures 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. However, with the advent of next-generation single-cell technologies and genome engineering tools it is now possible to address these questions. This project will combine next-generation single-cell ‘Multiomics’ with innovative developmental biology techniques and bespoke bioinformatics analyses, to resolve the complexities of cell fate decisions from the NPB.

Eligibility

Applicants must have obtained or be about to obtain a minimum Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline, such has biology, genetics or biomedicine.  Research experience in analysis of single cell gene expression or multiomics data is desirable.

Before you Apply

Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.

How to Apply

To be considered for this project you MUST submit a formal online application form – on the application form you must select FBMH Bicentenary PhD Programme - Full-time. If you select the incorrect programme your application cannot be considered. Full details on how to apply can be found on the Bicentenary Website

Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered.  If you have any queries regarding making an application, please contact our admissions team .

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