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EPIGENETIC AND STEM BIOLOGY Dr Veronique Azuara In the past few years the genetic code or 'blueprint' for humans has been completed and made publicly available. Despite this great achievement, we still do not fully understand how to translate the code. Nor do we know how to harness the genetic code to rebuild cells of damaged tissues or direct development of an individual from a single fertilised egg. What we do now know is that although this code is the same in every cell of the body, the code is interpreted differently in different types of cells. Part of the reason for this, is that the code (or DNA sequence) is folded and organised into so-called 'chromatin', which varies from cell to cell. Different conformations of the DNA within chromatin, termed the epigenome make certain parts of the code (i.e. genes) accessible and others inaccessible, depending on the cell type.
A major focus of our current research is to look at certain aspects of the DNAs chromatin structure in stem cells. Embryonic stem cells are remarkable cells because they can either self-renew or give rise to many different cell types. These attributes give a stem cell so-called pluripotent attributes. But in the process of generating different cell types, a stem cell must alter the structural organisation (i.e. chromatin) of its DNA code. Recently, we demonstrated that stem cells have a distinctive chromatin structure, where the DNA code is largely accessible. In contrast, when stem cells give rise to neurons, they go through extensive and predictable chromatin alterations. One such change that occurs is that genes important for maintaining the pluripotent state are rendered less accessible at the chromatin level, presumably because they are no longer needed. Meanwhile, neuron-specific genes become more accessible, preparing the DNA template to be copied and translated into a protein product. The changes that occur in chromatin organisation are the signature for stem cells choosing to become a nerve cell rather than any other cell type such as a muscle cell. We now intend to translate this information about chromatin structure in mouse stem cells to that of human stem cells. This will help us to understand how the genetic code is used, and design better strategies for turning stem cells into cells that are useful for treating spinal injuries and neuronal diseases such as Parkinson's disease if you wish to donate to this research please click here
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