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Sperm-Egg Phusion

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Unexpected connections between a phagocytic machinery and mammalian fertilizatio...

Unexpected connections between a phagocytic machinery and mammalian fertilization Fertilization is essential for a species to survive. Mammalian sexual reproduction requires the fusion between the haploid gametes sperm and egg to create a new diploid organism. Although fertilization has been studied for decade... see more

30/09/2024

VLAAMS INSTITUUT...

2M€

Project Budget: 2M€

Project leader

VIB VZW No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

PARTICIPATION DEPralty Sin fecha límite de participación.

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Financing granted El organismo H2020 notifico la concesión del proyecto The day 2024-09-30

ERC-2018-ADG: ERC Advanced Grant Scope:Objectives

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2 Participantes

VLAAMS INSTITUUT BIOTECHNOL...

2.50M€ | Leader

VIDRALA

279.41K€ | participant

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Project duration: 64 months Date Start: 2019-05-02
End date: 2024-09-30

Project leader

VIB VZW No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Project Budget 2M€

participation deadline Sin fecha límite de participación.

Project description Fertilization is essential for a species to survive. Mammalian sexual reproduction requires the fusion between the haploid gametes sperm and egg to create a new diploid organism. Although fertilization has been studied for decades, and despite the remarkable recent discoveries of Izumo (on sperm) and Juno (on oocytes) as a critical ligand:receptor pair, due to the structure of Izumo and Juno, it is clear that other players on both the sperm and the oocytes must be involved. While the focus of our laboratory over the years has been in understanding apoptotic cell clearance by phagocytes, we accidentally noted that viable, motile, and fertilization-competent sperm exposes phosphatidylserine (PtdSer). PtdSer is a phospholipid normally exposed during apoptosis and functions as an ‘eat-me’ signal for phagocytosis. Further, masking this PtdSer on sperm inhibits fertilization in vitro. Based on additional exciting preliminary data, in this ERC proposal, we will test the hypothesis that PtdSer on viable sperm and the complementary PtdSer receptors on oocytes are key players in mammalian fertilization. We will test this at a molecular, biochemical, cellular, functional, and genetic level. From the sperm perspective — we will ask how does PtdSer changes during sperm maturation, and what molecular mechanisms regulate the exposure of PtdSer on viable sperm. From the oocyte perspective — we will test the genetic relevance of different PtdSer receptors in fertilization. From the PtdSer perspective — we will test PtdSer induces novel signals within oocytes. By combining the tools and knowledge from field of phagocytosis with tools from spermatogenesis/fertilization, this proposal integrates fields that normally do not intersect. In summary, we believe that these studies are innovative, timely, and will identify new players involved in mammalian fertilization. We expect the results of these studies to have high relevance to both male and female reproductive health and fertility.

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