Principles of human development and germ cell program (360G-Wellcome-209475_Z_17_Z)

£2,750,000

<p>Specification of human primordial germ cells (hPGCs)&nbsp;occurs around gastrulation, a critical juncture when the specification of the primary somatic lineages&nbsp;also occurs. In combination with human preimplantation embryos, in<em> vitro</em> models and hPGCs from aborted fetuses, our objective is to elucidate the origin and properties of the early human germline.</p> <p>For&nbsp;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&nbsp;germ cell fate, and then respond to combinatorial effects of the critical transcription factors, which induce hPGC specification.&nbsp;Altogether, this study will&nbsp;reveal the organisation of the very early human embryo, and mechanisms of hPGC and somatic outcomes, which is essential for advances in regenerative&nbsp;medicine.</p> <p>Following hPGC specification, epigenetic resetting of the early human germline leads to extensive erasure of DNA methylation and epimutations&nbsp;in response to the critical regulators&nbsp;of chromatin organisation and nuclear architecture&nbsp;towards the epigenetic ground state. &nbsp;Some conserved resistant loci ('escapees') evade reprogramming. &nbsp;We will explore if some escapees have been exapted&nbsp;to function as&nbsp;regulatory elements. &nbsp;If so, this&nbsp;may have a crucial influence on&nbsp;human development, including brain development and neuronal diseases.</p> <p>&nbsp;</p> <p>&nbsp;</p>

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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
Planned Dates: End Date 2024-02-01T00:00:00+00:00
Planned Dates: Start Date 2018-02-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England