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Epigenetic and Signal Transduction Interactions in Development and Stem Cell Differentiation

ReferenceBBS/E/B/0000H331
Principal Investigator / Supervisor Dr Peter Rugg-Gunn
Co-Investigators /
Co-Supervisors
Institution Babraham Institute
DepartmentBabraham Institute Department
Funding typeResearch
Value (£) 48,140
StatusCurrent
TypeInstitute Project
Start date 01/09/2011
End date 31/08/2016
Duration60 months

Abstract

During early mammalian development, the embryo undergoes an important transition where cells become specialised and are orientated to be the building blocks of the future body. How this process is controlled remains poorly understood but it is important to study because it will provide insight in to how distinct cell types are formed in the embryo. Scientists are trying to mimic these events in order to control specialisation of stem cells. By better understanding how this process occurs, we may uncover new ways to turn stem cells into useful cell types, such as heart and liver, that we can use for cell-replacement therapies. I have chosen to study a protein called Ezh2, which regulates what genes are turned on and off, because we know that it has an essential role during this transition in mouse development. By studying mouse embryos at a very early stage in development, together with stem cells in culture, I will uncover how Ezh2 is involved in this process and also what are the signals that control Ezh2 itself.The first objective of this research is to identify the genes that Ezh2 is regulating during stem cell specialisation and also find out how Ezh2 is recruited to these particular sites in the genome. The second objective is to examine what happens to this set of genes when we genetically remove Ezh2 from the stem cells and also from the embryo – the prediction being that they will fail to be regulated properly and this should tell us exactly why Ezh2 is essential for this early stage of development. The third objective is to identify the signals that control the activity and recruitment of Ezh2 during stem cell specialisation, and this should explain how Ezh2 regulation is linked to other important processes that occur during development. This research will identify why Ezh2 is essential for the specialisation of cells during development. Understanding the detailed mechanisms of how this process occurs may lead to improved control over stem cells and our ability to use them for therapy. Ezh2 also has important roles outside of development, especially in the early stages of cancer where the normal process of regulating Ezh2 is lost. By better understanding how Ezh2 is controlled, we may identify new ways to detect this early warning sign and also to prevent this alteration from occurring.

Summary

unavailable
Committee Not funded via Committee
Research TopicsStem Cells
Research PriorityX – Research Priority information not available
Research Initiative X - not in an Initiative
Funding SchemeX – not Funded via a specific Funding Scheme
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