Chromatin remodeling and gene regulation in simple eukaryotes
Our laboratory is fascinated by events in the nucleus of eukaryotic cells and how these events impact on the phenotype of a cell. We work in the yeast S.cerevisiae and in mammalian cells in culture. We are asking questions such as:
How does the metabolic state of the cell affect the chromatin and transcription?
How does the metabolic state of the cell affect chromosome conformations, the higher order structures in chromatin?
How do differences in chromosome conformations relate to a cell’s phenotype?
The yeast work focuses on the yeast metabolic cycle (YMC). This is a type of synchronized growth where levels of transcripts change naturally as the cell population moves between different metabolic states related to growth or quiescence. This is a great model system for relating metabolism to all aspects of gene expression and also tells us about how cells age. The work in mammalian cells is focused on understanding the molecular basis of disease. In this work we use higher order structures in chromatin to predict how cells and people will respond, or not, to drugs and treatments and whether, or not, they are likely to develop a disease. We collaborate with a local spin-out company, Oxford Biodynamics, who have developed the EpiSwitch™ technology to detect chromosome conformations. We relate particular chromosome conformations to metabolism, chromatin and transcription to discover how they combine to affect the phenotype.