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PROJECT TITLE

Phospholipase C zeta (PLCzeta): Clinical prognosis, diagnosis, and treatment of oocyte activation deficiency

SUPERVISORS

Dr Kevin Coward

 

DESCRIPTION OF PROJECT

Oocyte activation is a fundamental step in fertilisation, involving inositol 1,4,5-trisphosphate (IP3)-mediated changes in intracellular calcium (Ca2+). In mammals, this manifests as a series of characteristic Ca2+ oscillations, beginning soon after gamete fusion, and persisting beyond the completion of meiosis. The frequency and amplitude of Ca2+ oscillations at fertilisation may not only be necessary for oocyte activation, but also equally important for subsequent embryogenesis.

Data strongly suggest that the testis-specific phospholipase C (PLC) isoform, termed PLCzeta (PLCζ) is responsible for eliciting the Ca2+ oscillations seen at fertilisation. Indeed, human sperm that routinely cause intracytoplasmic sperm injection (ICSI) failure exhibit a severely compromised pattern of Ca2+ release, and exhibit reduced/absent levels of PLCζ protein. Intriguingly, such sperm can achieve successful pregnancy and birth coincident with assisted oocyte activation (AOA) protocols.

However, there is significant concern regarding the fact that AOAs induce Ca2+ release in a manner that is very different from that seen endogenously. Purified recombinant human PLCζ protein may therefore represent a safer, more endogenous replacement for current AOA protocols in the treatment of oocyte activation deficiency and ICSI failure.

This project aims to enhance previous work carried out in Dr Coward’s laboratory towards the clinical translation of PLCζ as a valuable prognostic, diagnostic, and therapeutic tool. 

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TRAINING OPPORTUNITIES

Mutagenesis, recombinant DNA technology, protein expression and purification, mammalian cell culture, cRNA production, immunofluorescence and immunocytochemistry, gamete micromanipulation, mouse oocyte microinjection, ICSI, immunoblotting, imunnofluorescence, confocal microscopy.

As well as the specific training detailed above, students will have access to a wide-range of seminars and training opportunities through the many research institutes and centres based in Oxford.

Funding

The position is not currently funded and therefore the candidate will need to secure funding.