We collaborate internationally to establish methods of using stem cells to identify new drugs and treatments for degenerative disorders including cardiovascular diseases and Motor Neuron Disease. These diseases involve the loss of normal function in specific cell types and are often fatal. We are developing accurate and reproducible techniques to change cells directly from one cell type to another, including skin to nerve or heart cell lineages which are directly affected in our diseases of interest. These innovative techniques to control cell fate also depend upon ongoing research to understand the key molecular mechanisms that regulate early embryo development and tissue formation.
We aim to develop enhanced methods to change cells from one phenotype to another and to collaborate with others the use of these techniques in research to understand the molecular basis of inherited diseases. We are members of a large international collaboration which has shown that physiological levels of mutant TDP43 protein reduced survival in culture of both motor neurons and astrocytes.
This disease model provides the first opportunity to assess candidate small molecules for a protective effect. In this model there was no effect, either protective or harmful, of co-culture of these cells. This observation contrasts with the very harmful effect of glia carrying mutant SOD1 upon survival of motor neurons, both in vivo and in culture.
Methods of reprogramming cells are still slow and inefficient in contrast to the rapid change observed after nuclear transfer to oocytes. In collaboration with Sari Pennings and Shaoron Gao we are investigating mechanisms that reprogram gametes during fertilisation and early development in- search of the active molecules.