Our Research

We aim to elucidate the molecular mechanisms that control the assembly, maintenance and function of the kinetochore and broader mitotic spindle. We will build on the proteomic and microscopy techniques we have developed to unravel their regulation in detail, understanding how this controls chromosome segregation and cell division more generally, how it is involved in controlling cell fate decisions, and how these processes might go awry in development and cancer.

The lab has distinguished itself through its methodologies and rigorous, quantitative approach. We are exploiting our Synthetic Physical Interaction (SPI) and high-throughput imaging methods, as well as growing our collaborations and pursuing new state-of-the-art methodologies. We aim to integrate our findings, using computational and experimental methods to construct a systems level understanding of the kinetochore and its complex and dynamic role in the cell.

Our previous work has suggested that phosphorylation plays a central role in kinetochore control – something that we are exploring in detail by identifying and characterising key regulatory kinases and phosphatases. We will map where and when in the kinetochore these proteins act, and how they connect with other cell cycle processes. We aim to extend the SPI system to construct synthetic regulatory pathways using data analysis tools (machine learning approaches).

Our data suggest that phosphorylation is the key regulatory modification at the mitotic spindle - cell cycle-regulated phosphorylation peaks during mitosis. We are now using both or SPI system and computational approaches to try and tease out the regulatory network of phosphorylation at the mitotic spindle.

We are also fortunate to have a collaboration with a biophotonics group at Imperial College London that will allow us to use high-throughput, super resolution imaging to precisely map the location of kinetochore regulators. We are using this to explore some intriguing links between kinetochore function and DNA repair, focused on the role of the DNA repair protein Rdh54. 

We are committed to making all of our tools and data available online, partly through the BBSRC next generation imaging database. We have incorporated our SPI data on forced interactions into a web-tool and are working on adding our microscopy data too. This could serve as an open-access online resource for exploring spatial and temporal regulation within the cell.