Objective
Development from a totipotent zygote into an adult occurs essentially without changes in DNA sequences but involves epigenetic mechanisms. This includes modifications of histones and DNA such as methylation, which regulate expression of specific set of genes present in all cells. Similar mechanisms are also involved during differentiation of pluri potent stem cells. These modifications are however reversible, for example, when somatic nuclei re-acquire totipotency when transplanted into oocytes. There is also an extensive erasure of most of the pre-existing epigenetic information in primordial germ cells (PGCs) immediately after their entry into the developing gonads, which provides a unique opportunity to discover the mechanism of epigenetic reprogramming of the genome. PGCs until about E10.5 possess modifications of the DNA that are similar to those in somatic cells, such as DNA methylation of specific regulatory elements, as well as the inactive X chromosome. However, when PGCs enter into the developing gonads, this information is erased, rapidly and substantially by E12.5.
This process is prerequisite for subsequent totipotency of the zygote. I propose to identify and study the key genes involved in the erasure of epigenetic information from PGCs. PGCs will be isolated from genital ridges at E10 and from E11.5. Key candidate genes that are activated between E10.0 and E11.5 will be identified using Representational Difference Analysis (RDA) and micro-array analysis. Subsequently, verification of their expression patterns will be carried out by in situ hybridisation and real time RT-PCR on PGCs isolated from E9.5 to E12.5. Functional analysis of the candidates will involve cell-based assays in vitro, and siRNA in ES cells. These modified ES cells will be introduced into host blastocysts, and PGCs from the resulting fetuses will be analysed for their effects on epigenetic reprogramming. I will also examine if any of these factors are inherited in oocytes to determine.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics DNA
- medical and health sciences medical biotechnology cells technologies stem cells
- natural sciences mathematics pure mathematics mathematical analysis functional analysis
- medical and health sciences clinical medicine embryology
- natural sciences biological sciences genetics genomes
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2002-MOBILITY-3
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Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
CAMBRIDGE
United Kingdom
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