Phospholipase C zeta (PLCzeta): Clinical prognosis, diagnosis, and treatment of oocyte activation deficiency (Dr Kevin Coward)
Phospholipase C zeta (PLCzeta): Clinical prognosis, diagnosis, and treatment of oocyte activation deficiency
DESCRIPTION OF PROJECT
The incidence of infertility is rising and is estimated to affect 8 - 12% of couples worldwide; male factors are responsible for 25 - 30% of such cases. While assisted reproductive technology (ART)and intra-cytoplasmic sperm injection (ICSI) have revolutionized our ability to treat male factor infertility, total fertilization failure (TFF) still occurs in 5 - 20% of all IVF cycles and 1 - 3% of all ICSI cycles.
The principal cause of TFF following ICSI is oocyte activation deficiency (OAD), a condition in which the oocyte fails to undergo maturation and complete fertilization following sperm fusion. The principal causative factor for OAD is abnormalities in the structure and function of PLCz, a sperm-specific protein that normally initiates characteristic oscillations of intracellular Ca2+ in the ooplasm for several hours after gamete fusion.
These oscillations regulate the expression of Ca2+-sensitive transcription factors which induce several physiological processes ultimately activating the embryonic genome and generating a viable early embryo. Consequently, PLCz is a fundamental requirement for successful fertilisation.
Since 2008, the Coward Laboratory has made several advances in our understanding of the role of PLCz in OAD and how this condition might be diagnosed and treated. Our close collaboration with The Fertility Partnership (TFP) has allowed us to recruit a specific patient population with OAD and recurrent ICSI failure (along with controls) and develop immunofluorescence and genetic diagnostic assays. However, while we can diagnose patients with PLCz-deficiency, we are currently unable to provide a safe and endogenous therapeutic agent.
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.
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.
The position is not currently funded and therefore the candidate will need to secure funding.