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Stem cell differentiation and ageing
All mammals, including humans, start life as a fertilised egg that divides to form an embryo. Each cell in an early embryo then differentiates into various cell types (e.g. skin, heart, muscle, neurons, liver cells) which are organised in specific ways to form tissues, organs and, eventually a complete body.
But what controls all this is mostly unknown. And of course, everyone has a limited lifespan. After birth, we only grow up and get older. Our genes are carried on coiled strips of genetic material, the chromosomes. At the end of each chromosome are short pieces of DNA called telomeres. These are structures which have been shown to play a role in the ageing process. Telomeres are long when we are young, but bits of the DNA in these structures are gradually lost and the telomeres get progressively short as we get older. What regulates the telomere length and how telomeres affect cell proliferation, repair of ageing tissues and cell function is not fully understood.
Our research focuses on two areas:
1) Understanding how cells from early embryos differentiate into nerve and liver cells. We use embryonic stem cells (ES cells) for this work because they provide the most information about how the body develops so many different types of cell. Our laboratory has established several methods to make ES cell becoming neurons and liver cells, enabling us to study the cellular and molecular changes during this process.
2) We also research the molecular mechanisms that regulate telomere length in embryonic stem cells and their differentiated cells. Telomeres are longer and more stable in ES cells because they have a substance, telomerase, that maintains their lengths. After ES cells become differentiated, they lost active telomerase and telomeres become progressively shorter each the differentiated cells divide. This special feature of ES cells also provides a unique system to gain understanding of the mechanisms that regulate telomerase expression and telomere structure.
Our research will continue help to improve understanding of normal early human development and many common diseases, such as cancer. Substances that we find are important in specific cell differentiation are likely to help the development of new drugs for various diseases. In addition, the differentiated neural and liver cells may also be useful as a test-bed for the evaluation of new drugs, and tissue transplantation.