A BBSRC sLola-funded program to understand how shape-shifting proteins control cell division

An ambitious project aiming to decipher the function of intrinsically disordered protein regions (IDRs) has won funding from the BBSRC's Strategic Longer and Larger Grants. Whilst many proteins are known to adopt well defined 3D structures, all proteomes have numerous intrinsically disordered proteins (IDPs) as well as hybrid proteins possessing ordered domains and intrinsically disordered regions (IDRs). IDRs are sections of protein with no fixed shape; they are capable of shape-shifting and adopting different structures or no structure at all depending on their local environment. 

Dr Fanni Gergely and her co-workers at the Department of Biochemistry, University of Oxford, will work with teams from the School of Chemistry, School Medicine and the Astbury Centre at the University of Leeds to develop new tools to study IDRs. Together they aim to decipher the mechanisms by which groups of IDRs change shape, how that impacts on the network of interactions and therefore cell function, ultimately revealing the cellular roles these groups of IDRs play in health and disease.

The project centres on the Aurora A kinase – a protein which plays a crucial role in multiple cellular processes including cell division, gene expression and ciliogenesis. Aurora A controls these events by relying on interactions with specific IDRs; this grant will use chemical and biological probes to unpick how this network of IDRs co-ordinates Aurora A function in cells. Dr Gergely said: “I am truly excited to work with my Leeds-based co-investigators and collaborators on this challenge. This ambitious, multidisciplinary project will yield unprecedented insights into how Aurora-A co-ordinates mitotic spindle assembly, a longstanding interest of our group. Furthermore, the tools we develop could unlock the true potential of Aurora-A as a drug target and provide proof-of-concept for application to other systems of IDRs with implications to many areas of biology”. 


Localisation of Aurora kinases to the mitotic spindle is controlled by interactions with intrinsically disordered proteins. Active Aurora kinases (green), DNA (blue) and microtubules (red). Credit: Isabel Peset



  1. BBSRC News: Four ground breaking new projects set to expand the frontiers of bioscience knowledge https://bbsrc.ukri.org/news/fundamental-bioscience/2020/four-ground-breaking-new-projects-set-to-expand-the-frontiers-of-bioscience-knowledge/


Fanni Gergely
2nd October 2020