Decoding the architecture of cellular “antenna”: molecular mechanisms of ciliogenesis

Supervisors:

• Dr Robert Mahen rm722@le.ac.uk 
• Dr Rob Hirst
• Dr Emma Hesketh

A fully funded PhD position is available to study the formation of centrosomes and cilia in the laboratory of Dr Robert Mahen at the University of Leicester, UK.
Project highlights

• Map the architecture of cilia using light microscopy.
• Engineer human organoids.
• Use image analysis to observe cilia assembly in real time.

Project summary

Our ability to breathe, see, hear and smell, as well as our normal bodily development, depends on cilia. Cilia are found throughout the body as hair-like protrusions on almost all cells, where they act as "antenna", sensing and relaying external signals that govern human development and tissue homeostasis. About 1 in 1000 people have defects in ciliary assembly and function, causing a broad range of different diseases. More than 35 of these diseases are termed ciliopathies, including conditions such as Usher syndrome, Joubert syndrome, primary cilia dyskinesia, and polycystic kidney disease. They present with many different symptoms, including loss of vision, brain anomalies, breathing difficulties, infertility, and kidney failure. Although there are numerous different ciliopathies with wide-ranging symptoms, there are no cures for any of them, and ciliopathy treatments primarily consist of managing these degenerative pathologies. A major hurdle preventing ciliopathy treatment and diagnosis is our insufficient comprehension of the basic processes by which cilia are assembled and maintained within the body in functionally normal cells.

This PhD project offers an exciting opportunity to investigate ciliogenesis and understand the fundamental molecular mechanisms underlying it. You will use a combination of cutting-edge microscopy and organoid cell culture techniques, to understand how cilia function in human cells. Using state-of-the-art high-resolution live-cell imaging, CRISPR/Cas9 gene editing, and super resolution imaging, you will explore the spatiotemporal recruitment of key proteins during the transition from centriole to basal body.

Our initial experiments have already revealed never-before-seen aspects of cilia morphology and function that demonstrate the importance and potential of these approaches. Together, this will help us to better understand how cilia form, with a long-term goal of detecting and treating the diseases that arise from cilia dysfunction.

Research environment
Based at the University of Leicester, you will join a collaborative research group supported by the Academy of Medical Sciences Springboard Award. You will have access to world-class imaging facilities (including super-resolution microscopy and cryo-Electron microscopy) and receive comprehensive training in advanced cell biology, molecular cloning, and computational image analysis. You will also join a cohort of PhD students with shared training opportunities as part of The Division of Molecular and Cell Biology, and the Leicester Institute for Structural and Chemical Biology

Candidate requirements
Our main selection criteria are curiosity, enthusiasm and intellectually flexibility, but candidates with a strong background in biomedical sciences, biochemistry, cell biology, chemistry, or biophysics will be competitive.

References

cNap1 bridges centriole contact sites to maintain centrosome cohesion.
Mahen, R. PLOS Biology. 2022. 20(10). https://pubmed.ncbi.nlm.nih.gov/36282799/Stable centrosomal roots disentangle to allow interphase centriole independence.

Mahen R. PLOS Biology. 2018. 16(4). https://pubmed.ncbi.nlm.nih.gov/29649211/

Continuous polo-like kinase 1 activity regulates diffusion to maintain centrosome self-organization during mitosis. Mahen R et al. PNAS. 2011 108(22). https://pubmed.ncbi.nlm.nih.gov/21576470/

Please refer to the additional information and How to Apply advice below before using the application link at the bottom of the page to submit your application.