Role of epigenetic mechanisms in random X chromosome inactivation ex vivo and in vivo. (360G-Wellcome-201369_Z_16_Z)
Developmental progression is linked to accumulation of epigenetic information mainly in the form of chemical modifications of the chromatin. One of the most striking examples of that is random X chromosome inactivation (XCI) in female mammalian embryos. This process is dependent on coating of one X chromosome by a long non-coding RNA, Xist. This in turn promotes rapid and dramatic remodelling of the chromatin. The functional relevance and exact spatio-temporal dynamics of this process remains elusive. Here I propose to address these questions by using an integrated approach. Firstly I will use an ex vivo embryo culture system to monitor the dynamics of XCI. I will further integrate that information with single cell and population based epigenomic to generate in vivo and in vitro datasets accounting to a roadmap for XCI. I aim at identifying the initial stages of epigenetic programming leading to transcriptional repression as well as genomic loci involved in nucleating these changes. I will finally address the functional relevance of X chromosome epigenetic programming by using gene knockout models and genome-wide single cell transcriptomics approach. Such work will have wide-raging implications beyond the field of XCI and can be extrapolated into other epigenetic regulatory mechanisms.
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Grant Details
Amount Awarded | 250000 |
Applicant Surname | Zylicz |
Approval Committee | Basic Science Interview Committee |
Award Date | 2016-04-19T00:00:00+00:00 |
Financial Year | 2015/16 |
Grant Programme: Title | Sir Henry Wellcome Postdoctoral Fellowship |
Internal ID | 201369/Z/16/Z |
Lead Applicant | Dr Jan Zylicz |
Partnership Value | 250000 |
Planned Dates: End Date | 2020-03-15T00:00:00+00:00 |
Planned Dates: Start Date | 2016-07-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | East of England |
Sponsor(s) | Prof William Harris |