Defining the mechanisms of induced pluripotency. (360G-Wellcome-101861_Z_13_Z)

£1,861,906

My research has centred on nuclear reprogramming since my PhD. As an independent Principal Investigator I have developed unique systems to better investigate the process of induced pluripotency. This resulted in the identification of Nanog and culture environment as key players and has helped re-define our understanding of the biological roles of Oct4. As a senior principal investigator I want to build on this platform and on exciting new findings from my lab. Specifically, I will focus on mecha nisms of induced pluripotency and on parallels with in vivo phenomena. 1-Define mechanistically the cell state transition leading to the acquisition of a naive pluripotent cell state. New data from our lab shows that Nanog and culture environment work synergistically on reprogramming mechanisms. We also found that depending on the culture environment, defined ES-level of Oct4 expression instructs either a naive pluripotent cell state or cell differentiation. My aim is to further explore t he relationships between key players and understand how the observed reprogramming mechanisms are regulated. I also want to fully define the direct molecular reprogramming mechanism of Nanog by investigating how its interactions with co-factors, mostly epigenetic regulators, affect its capacity to reprogram. 2-Investigate parallels between mechanisms of reprogramming and analogous biological processes. We were the first to draw a parallel between induced pluripotency and embryonic developm ent. Our future aim is to investigate how general is this concept by assessing if identified nuclear reprogramming mechanisms are recapitulated during the acquisition of the naive epiblast in the early embryo.

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Grant Details

Amount Awarded 1861906
Applicant Surname Rebelo da Silva
Approval Committee Science Interview Panel
Award Date 2013-07-10T00:00:00+00:00
Financial Year 2012/13
Grant Programme: Title Senior Research Fellowship Basic
Internal ID 101861/Z/13/Z
Lead Applicant Dr Jose Carlos Rebelo da Silva
Partnership Value 1861906
Planned Dates: End Date 2019-09-03T00:00:00+00:00
Planned Dates: Start Date 2014-03-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England
Sponsor(s) Prof Austin Smith