Jake Elton

Profile

Project Title: Membrane Shaping in Cilia Formation and Function

Summary: 

Cilia are microtubule-based structures that have crucial functions in a diverse range of biological processes. They are involved in essential processes including sensing, intracellular signalling and motility. Highlighting their importance, dysfunctions in cilia, termed ciliopathies, are implicated in a range of human diseases.

Cilia are templated by centrioles (then called basal bodies), a process that involves extensive membrane remodelling events that are currently poorly understood. The basal body-associated Chibby1-FAM92 complex is involved in some of these processes. Mother centriole-bound Chibby1 (Cby1) is a small, conserved coiled-coil protein that directly recruits FAM92A, a protein that largely consists of a membrane binding BAR domain. Knockout and knockdown data in different model organisms suggest that this complex facilitates ciliogenesis by promoting the early stages of ciliary axoneme growth and membrane attachment of the basal body.

What is currently largely lacking is a mechanistic understanding of how this crucial protein complex functions, including its organisation, regulation and the structural basis of its membrane shaping activity.

The proposed PhD project focuses on providing this information mainly through using protein biochemical and structural but in later stages also cell biological approaches. Through this project, we will shed light on understudied yet crucial steps in cilia formation and will deliver tools that allow us to manipulate the local membrane shape to further address the in vivo importance of defined membrane curvature in cilia formation and function.

Supervisor:

• Dr Mark van Breugel

Research