Understanding the molecular architectures of centrosomes and cilia

Supervisor(s)

Dr Takashi Ochi

Project description

This PhD project is to determine the molecular assembly mechanism of a structure of the centriole / basal body by a combined approach of structure biology and biochemistry.

Centrosomes play central roles in cell division by nucleating microtubules that equally divide duplicated chromosomes into two dividing cells. The failure of this process can cause loss of genomic information, which can result in cancer. In addition, centrosomes are essential for generating cilia because the core structure of the centrosome (called centriole) becomes the base of the cilium. The centriole is called the basal body at the cilium, but they are essentially the same structure. Cilia can be divided into two types: non-motile and motile cilia. Non-motile cilia (primary cilia) play a role in cellular signalling whereas motile cilia generate fluid flow (e.g. in airway to exclude mucus) and locomotion (e.g. in sperm). These ciliary functions are important for normal development and activity of our body.

Since centrosomes and cilia are highly-ordered protein complexes, they must maintain correct architectures for their normal functions. Indeed, mutations within many centrosomal and ciliary genes result in their structural defects, and can cause ciliopathies, which are characterised by abnormal body development. Therefore, understanding how each protein contributes to build these organelles is important. However, we know little about exact contributions of most of centrosomal and ciliary proteins to their structures. To resolve this problem, my group currently focuses on determining the structure that is shared between the centrosome and cilium.

During the project, the successful candidate will use bacterial, insect and human cells for protein, production, purification and characterisation. Also, the student will have opportunities to learn how to use our state-of-art cryo-electron microscopes and analyse their data, and how to determine protein structures using X-ray crystallography.

https://www.ochilab.org

Entry requirements

Candidates should have, or be expecting, a 2.1 hons at Undergraduate level or above, in a relevant subject. If English is not your first language, you will need a recognised English Language qualification to be admitted onto any of the University's degree programmes: https://www.leeds.ac.uk/info/123100/admissions/143/entry_requirements

How to apply

Please apply online https://studentservices.leeds.ac.uk/pls/banprod/bwskalog_uol.P_DispLoginNon

Please include supervisor name and project title.  A research proposal is not required.  Please upload a CV and transcripts.

How to apply (email)

fbsgrad@leeds.ac.uk

How to apply (phone)

+44 (0)113 343 8186