Cel Mammalian sperm activate the oocyte at fertilisation by triggering a calcium-mediated pathway via PLCζ, a sperm-specific phospholipase. PLCζ deficiency is linked to human infertility, a condition that affects 1 in 7 couples. While intra-cytoplasmic sperm injection (ICSI) can rescue many types of male infertility, 1 – 5% of cases fail due to PLCζ-deficiency. While artificial activating agents are available, such chemicals do not initiate activation in an endogenous manner. Recombinant PLCζ thus represents a safer therapeutic option. However, we do not yet know how PLCζ interacts with oocyte-based factors in order to regulate functionality. Current opinion is that an unidentified protein resides within the ooplasm upon vesicles containing the substrate for PLCζ. Identifying this factor, and optimising the manner in which oocyte activation deficiency (OAD) can be diagnosed and treated, is a key clinical remit. Of equal concern is that the host laboratory showed that clinical treatments, such as cryopreservation, can cause detrimental effect upon PLCζ in human sperm. Consequently, this proposal has two objectives: 1) identify the oocyte-factor that interacts with PLCζ via the use of protein-protein interaction technologies, and 2) evaluate the impact of clinical procedures upon gamete proteins that play a critical role during activation. Research will involve human gametes sourced from the Oxford Fertility Unit, along with murine and bovine animal models. The proposal is targeted to (a) improve our understanding of PLCζ function, (b) establish whether the oocyte-interacting protein represents a novel diagnostic marker for OAD, and (c) develop our understanding of how clinical procedures can influence proteins in human gametes. While the proposal is primarily targeted to human reproductive medicine, results will be equally applicable to animals of economic interest, such as the controlled breeding programmes used for equine and bovine species. Dziedzina nauki natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsmedical and health sciencesclinical medicinegynaecologyreproductive medicinesocial sciencessociologydemographyfertility Program(-y) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Temat(-y) FP7-PEOPLE-2013-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Zaproszenie do składania wniosków FP7-PEOPLE-2013-IEF Zobacz inne projekty w ramach tego zaproszenia System finansowania MC-IEF - Intra-European Fellowships (IEF) Koordynator THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD Wkład UE € 299 558,40 Adres WELLINGTON SQUARE UNIVERSITY OFFICES OX1 2JD Oxford Zjednoczone Królestwo Zobacz na mapie Region South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Gill Wells (Ms.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych
