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How does twitchy link to ciliary function in sperm cells


   Faculty of Biology, Medicine and Health


About the Project

Cilia are hair-like structures that project from the surface of cells and act as “cellular antennae,” sensing and relaying information from the environment. Some cilia, known as flagella, are motile. Since most cells in the human body are ciliated, defective cilia can cause a wide range of diseases, termed “ciliopathies.”

Most cilia form as a cellular protrusion and the components required to assemble these “primary cilia”, and for their function, are made in the cell body. They must pass through a selective barrier called the “ciliary gate” that separates the primary cilium compartment from the rest of the cell. In contrast, motile sperm flagella form within the cytoplasm. How the proteins required for its assembly and function are added to the flagellum is not well understood.

Many ciliary proteins are conserved in the fruit fly, Drosophila, where cilia are restricted to sensory neurons (compartmentalised cilia) and sperm cells (formed in the cytoplasm). Mutations in these ciliary genes give rise to adult flies with locomotor defects and/or male infertility. We have identified mutations in a gene that we have called “twitchy” as adult flies are severely uncoordinated and are unable to balance, walk or fly. Orthologues of twitchy function as part of the ciliary gate found in compartmentalised cilia. However, twitchy is also expressed in sperm cells and RNAi-mediated knockdown of twitchy results in male infertility. This implies that twitchy has a function in sperm cells that is different from its function in compartmentalised cilia.

This project will address how twitchy, and other “transition fibre” proteins that form the ciliary gate of compartmentalised cilia, function in the formation of motile sperm by analysing:

1. where and when transition fibre proteins act in sperm and

2. by identifying the molecules that transition fibre proteins interact with in sperm cells.

Entry Requirements

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area/subject. Candidates with previous laboratory experience are particularly encouraged to apply.

How To Apply

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the appropriate subject title.

For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences.

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/”


Funding Notes

Applications are invited from self-funded students. This project has a Band 2 fee. Details of our different fee bands can be found on our website View Website

References

Hodge SH, Watts A, Marley R, Baines RA, Hafen E, MacDougall LK (2021). Twitchy, the Drosophila orthologue of the ciliary gating protein FBF1/dyf-19, is required for coordinated locomotion and male fertility. Biol Open. 10: bio058531. doi: 10.1242/bio.058531.
Garcia-Gonzalo FR and Reiter JF (2017). Open sesame: how transition fibers and the transition zone control ciliary composition. Cold Spring Harb Perspect Biol 9: a028134 doi: 10.1101/cshperspect.a028134.
Avidor-Reiss T and Leroux MR (2015). Shared and Distinct Mechanisms of Compartmentalized and Cytosolic Ciliogenesis. Curr Biol 25: R1143-R1150 doi: 10.1016/j.cub.2015.11.001
Jana et al. (2016) Cilia 5: 22: Drosophila melanogaster as a model for basal body research. doi:10.1186/s13630-016-0041-5.
Fabian L and Brill JA (2012). Drosophila spermiogenesis: big things come from little packages. Spermatogenesis 2: 197–212. doi: 10.1016/j.semcdb.2016.06.010.

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