PhD project

PhD project

How membrane proteins are trafficked into cilia for sensory functions

Supervisor: Anthony Roberts & Katarina Toropova

Cilia are organelles on the surface of eukaryotic cells that are packed with membrane proteins. In humans, ciliary membrane proteins are responsible for detecting light, smell, morphogens, and ligands involved in complex processes such as appetite control. Thus, trafficking of membrane proteins into cilia is fundamental to human health, and defects in this process are associated with blindness, anosmia, developmental defects, and obesity, among other conditions. The goal of this project is to use cell biology approaches, particularly live-cell fluorescence microscopy, cryo-ET, and genome editing, to elucidate how membrane proteins are trafficked into cilia. To enter cilia, it is believed that membrane proteins must 1) attach to transport ‘trains’ that travel along the microtubules of cilia, whose structure we recently determined and 2) pass through a gate (the ‘transition zone’) at the base of the cilium, which is one of the most mysterious portals in the cell. By elucidating these processes, this project has the potential to uncover fundamental mechanisms of cellular biology and the basis for human disease states affecting multiple organ systems.

Keywords:

  • Biochemistry, Biophysics, Cell Biology, Molecular Biology, Structural Biology

Publications:

  • IFT-A Structure Reveals Carriages for Membrane Protein Transport into Cilia (2022) Hesketh SJ, Mukhopadhyay AG, Nakamura D, Toropova, K Roberts AJ. Cell, 185(26):4971-4985 PMID: 36462505
  • Intraflagellar Transport Trains and Motors (2020) Webb S, Mukhopadhyay AG, Roberts AJ. Seminars in Cell & Developmental Biology, 107:82-90 PMID: 32684327
  • Composition, organization and mechanisms of the transition zone, a gate for the cilium (2022) Park K, Leroux MR. EMBO Rep. 23(12):e55420. PMID: 36408840

Roberts lab

Investigating how motor proteins generate movement and spatial organisation within living cells

Toropova lab

Discovering how molecular machines perform essential cellular functions using cryo-electron microscopy/tomography and live fluorescence imaging.

Our PhD course

Doing a DPhil in Molecular Cell Biology in Health and Disease at the Dunn School is the best way to start your career.