Group Leader

Stem Cell Biology and Developmental Genetics

The National Institute for Medical Research (London, UK)

Genome integrity and stem cell function

Asymmetric cell division is the process by which one cell divides to give two cells with different fates. Repeated asymmetric divisions allow a fertilized egg to generate diverse cell types during development, and in adult stem cell populations repeated asymmetric divisions maintain the stem cell population while simultaneously generating new, differentiated cells. The goal of our lab is to determine how cellular asymmetry is established and maintained over multiple divisions to create cell lineages. Specifically, we focus on understanding how asymmetry of the mitotic spindle - the machinery that segregates chromosomes during division - affects how genetic information is accurately passed down to daughter cells. Our model system is the budding yeast, Saccharomyces cerevisiae, which shows patterns of asymmetric division like those of more complex organisms. We employ high-throughput fluorescence microscopy techniques that allow us to rapidly screen the localization, levels and dynamics of all yeast proteins and integrate them into a visual dataset. Using these tools, we aim to identify the conserved mechanisms controlling asymmetric division, lineage specification and mitotic spindle function. For example, we are testing whether components of the kinetochore, a protein complex that anchors chromosomes to the spindle, is involved in selective asymmetric segregation of the centromere sequences to which they bind. We are also exploring emerging links between the kinetochore and the process of DNA repair. As part of these studies we are working to construct a systems-level microscopy dataset comprising images that describe the localization and concentration of every yeast protein, throughout the cell cycle and in every viable yeast mutant. This bioinformatic resource would help us understand how proteins operate together to control cellular functions.