Cellular responses to environmental change
Cells must express the correct genes to the correct level to thrive in any given environment. This may or may not be possible given their existing genetic information. Our research questions are:
How do cells decide which genes to express?
How is this decision influenced by epigenetic memory?
Can cells alter their genomes in the face of environmental challenges?
Do young and old cells react in the same way?
We focus on molecular mechanisms that link a cell's perception of the environment to its genome:
Control of gene expression and regulatory non-coding RNAs
Histone modifications and chromatin structure
Replication and recombination
Overall, we ask how cells process information about their environment to yield the appropriate gene expression response, and how this informationn is applied as they adapt to challenging new environments
Can cells control and direct mutations?
Is ageing a strategy for adaptation?
We tend to think of genomes as long-term stable repositories of information, providing all the information required to produce an organism. However, genomes can change, and not just over evolutionary timescales. Genome changes are a hallmark of cancer, but it is increasingly clear that some genetic loci are very prone to change in healthy cells during the lifespan of various organisms. We have discovered that mutations are actively stimulated at particular loci in response to particular environments, suggesting that organisms have much more control of their genomes than we normally consider. We are now asking how cells can stimulate mutations in a controlled manner, and how they process environmental information to select target genes.
The ageing process is of great societal interest, yet basic questions such as “Why do we age?” remain poorly answered. We have recently proposed that what we now know as ageing started as an process by which cells adapt to changing environments. Although we see age-linked dysregulation at the genetic, epigenetic, gene expression and phenotypic levels as a driver of pathology, this dysregulation makes the cell population much more heterogeneous, giving far greater capacity to survive and adapt to environmental change. We are studying the epigenetic and genetic changes in ageing cells to elucidate the underlying drivers and control mechanisms of cellular ageing.