Phd à United States

Project Description

Normal animal reproduction depends on the appropriate production of gametes – sperm and egg, and on their successful interaction (fertilisation). Sperm are extremely specialised cells; their success in fertilisation requires them to be free living, motile, and able to fuse with the egg to activate embryonic development. About 20% of the protein coding genes in the genome are exclusively or almost exclusively expressed in testes. The function of some of these genes is known, for example the transition proteins and protamines that remodel the sperm DNA. However, the biological function of the majority of testis-specifically expressed proteins has never been determined. They are members of the Unknome – the proteome of unknown function.

In this project you will systematically analyse the functions of the testis Unknome proteins, exploring both lineage specific proteins and proteins more widely conserved in evolution. You will capitalise on the extensive genetic resources available for fruit flies (D. melanogaster), particularly the large collections of mutants including those derived from gene disruption projects, including an ongoing CRISPR screen that aims to mutate every gene in D. melanogaster. You will assess the phenotypes of flies mutant for testis unknome genes, and thus determine their role in fertility.

Drosophila spermatogenesis is particularly amenable to cytological analysis. Testes from young adult flies contain all stages of spermatogenesis, from stem cells through to mature sperm. Defects in many critical cell biology processes, such as stem cell maintenance, cell division, mitochondrial morphogenesis, axoneme elongation and nuclear shaping are readily identified by phase contrast microscopy, with the opportunity for more detailed analysis via imaging of GFP-tagged marker proteins or immuno-fluorescence. Fertility assays will reveal any defects in the fly strains that are able to produce morphologically normal sperm. You will be able to select one or more (groups of) genes that you find particularly interesting for more in depth analysis.

Some of the testis unknome proteins are conserved to mammals. You will have the opportunity to investigate how these genes are important for mammalian sperm function, to complement the fly work. The localization of homologous gene products in mouse testis and mouse or pig spermatozoa will be studied with immunocytochemistry using custom made polyclonal antibodies. If proteins are surface localized the effect of antibodies on sperm motility, mitochondrial activity, the acrosome reaction or sperm induced egg fusion will be assayed.

How to apply:

You can apply online - consideration is automatic on applying for a PhD in Biosciences

Please use our online application service athttps://www.cardiff.ac.uk/study/postgraduate/research/programmes/programme/biosciences-phd-mphil-md

Please specify that you are applying for this particular project, the supervisor and source of funding.

Information on the application process can be found here

http://www.cardiff.ac.uk/study/postgraduate/applying

Academic criteria:Applicants should have obtained, or be about to obtain, a first or upper second-class UK honours degree, or the equivalent qualification gained outside the UK, Applicants with a lower second class will only be considered if they also have a Master’s degree. Please check the entry requirements of the home institution for each project of interest before completing an application. Academic qualifications are considered alongside significant relevant non-academic experience.

English requirements:If English is not your first language you will need to meet the English language requirements of the university that will host your PhD by the start of the programme. Please refer to the relevant university website for further information.