Principles of human development and germ cell program (360G-Wellcome-209475_Z_17_Z)
Specification of human primordial germ cells (hPGCs) occurs around gastrulation, a critical juncture when the specification of the primary somatic lineages also occurs. In combination with human preimplantation embryos, in vitro models and hPGCs from aborted fetuses, our objective is to elucidate the origin and properties of the early human germline. For the mechanism of the hPGC fate, we will use experimental models that simulate early human development. We aim to investigate how cells gain competence for germ cell fate, and then respond to combinatorial effects of the critical transcription factors, which induce hPGC specification. Altogether, this study will reveal the organisation of the very early human embryo, and mechanisms of hPGC and somatic outcomes, which is essential for advances in regenerative medicine. Following hPGC specification, epigenetic resetting of the early human germline leads to extensive erasure of DNA methylation and epimutations in response to the critical regulators of chromatin organisation and nuclear architecture towards the epigenetic ground state. Some conserved resistant loci ('escapees') evade reprogramming. We will explore if some escapees have been exapted to function as regulatory elements. If so, this may have a crucial influence on human development, including brain development and neuronal diseases.
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Grant Details
Amount Awarded | 2750000 |
Applicant Surname | Surani |
Approval Committee | Science Interview Panel |
Award Date | 2017-11-28T00:00:00+00:00 |
Financial Year | 2017/18 |
Grant Programme: Title | Investigator Award in Science |
Internal ID | 209475/Z/17/Z |
Lead Applicant | Prof Azim Surani |
Partnership Value | 2750000 |
Planned Dates: End Date | 2025-02-01T00:00:00+00:00 |
Planned Dates: Start Date | 2018-02-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | East of England |