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Investigating the structural and molecular mechanisms of male fertility by cryo EM


   Leeds Institute of Molecular Medicine


About the Project

In this project you will study the structure and function of macromolecular complexes found in male Drosophila seminal fluid that are essential for fertility. Working at the Astbury Centre, University of Leeds, UK, you will solve structures of these complexes using cutting edge structural biology techniques (cryo electron microscopy, cryo electron tomography, cryo electron crystallography, X-ray crystallography), and interrogate their function in vitro and in vivo using biochemical methods and fly genetics.

Drosophila male seminal fluid contains a highly density of mysterious tubules, ~700 Å in diameter, that are synthesised by the accessory (prostate) gland and transferred to the female alongside sperm during mating. Despite being identified over 50 years ago, the structure and function of these filaments remains a mystery [1-3]. In our very recent work we have also identified a new, previously unreported macromolecular species in Drosophila seminal fluid of unknown structure and function.

Working jointly between the labs of Dr Joe Cockburn and Prof Elwyn Isaac, you will solve the structures of these mysterious complexes and investigate the molecular mechanisms by which they support male fertility. Our hypothesis is that these structures promote male reproductive success by effecting favourable post-mating responses in the mated female (e.g. increased egg laying and reduced receptivity to other males) [4,5]. Indeed, mated female flies store sperm for considerable periods of time, producing hundreds of fertilised eggs over several weeks following a single mating. Drosophila is a widely used animal model for studying reproduction [6] and this project will therefore be highly impactful within the fertility field, whilst training you in a range of cutting-edge and in-demand structural biology techniques.

Prior structural biology experience is not required for this project as all training will be provided; however, an interest in structural biology and a willingness to learn these techniques is essential. Basic biochemistry lab skills would be advantageous.

For more information please contact Dr Joe Cockburn ().


Funding Notes

Self-funded students: International or domestic self-funded or scholarship/fellowship PhD students are always welcome to apply. International students must have a good command of both written and spoken English. Most importantly, bench fees will be required if you are self-funded. Applications can be made throughout the year.

References

1. Acton, A.B. An Unusual Ciliumlike Process. J Cell Biology 29, 366-369 (1966).
2. Tandler, B., Williams, D.l. & Ehrman, L. Unusual Filamentous Structures In Paragonia Of Male Drosophila. J Cell Biology 38, 329-336 (1968).
3. Perotti, M.E. Microtubules As Components Of Drosophila Male Paragonia Secretion. J Submic Cytol 3, 255- & (1971).
4. Fricke C, Koppik M. Male reproductive ageing: a tale of the whole ejaculate. Reproduction 158(6):R219-R229 (2019)
5. Jang YH, Chae HS, Kim YJ. Female-specific myoinhibitory peptide neurons regulate mating receptivity in Drosophila melanogaster. Nat Commun 8(1):1630. (2017)
6. Wilson C, Leiblich A, Goberdhan DC, Hamdy F. The Drosophila Accessory Gland as a Model for Prostate Cancer and Other Pathologies. Curr Top Dev Biol 121:339-375 (2017)

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