SubsidieMeestersMechanism of vertebrate sperm-egg recognition and fusion
This project aims to elucidate the molecular mechanisms of sperm-egg recognition and fusion in vertebrates using zebrafish, with the goal of reconstituting a functional fertilization interface in vitro.
Projectdetails
Introduction
The life of every sexually reproducing being can be traced back to a singular event: the fusion of sperm and egg. Gamete fusion is perhaps the most critical step in the process of fertilization. However, the mechanisms underlying vertebrate sperm-egg fusion and the events that precede it (sperm-egg recognition) are largely unknown. Uncovering the molecular machinery and biophysical mechanisms mediating sperm-egg recognition and membrane fusion in vertebrates is therefore one of the biggest challenges in fertilization research.
Project Aims
In this project, we aim to uncover the mechanistic principles of vertebrate fertilization by exploiting the unique advantages of zebrafish as a vertebrate model in combination with in vitro reconstitution assays. We will focus on two main questions:
- What is the molecular mechanism of sperm-egg recognition?
- What are the molecular and biophysical principles underlying sperm-egg fusion?
Methodology
To identify new essential components of the sperm-egg recognition and fusion machineries, we will develop candidate and unbiased screening approaches. We will combine functional studies in vivo, using phenotypic, genetic, biochemical, and advanced high-resolution imaging approaches, with mechanistic studies in vitro, using structural and reconstitution assays. This will allow us to rigorously determine:
- Requirement and sufficiency
- Causal relationships
- Spatiotemporal dynamics
- Mechanisms
Our recently discovered fertility factors Bouncer (sperm-egg recognition) and Dcst1/2 (sperm-egg fusion) provide precise entry points for screens and for functional and mechanistic studies.
Overall Goal
Overall, our goal is to mechanistically understand how sperm and egg recognize and bind to each other, and how their membranes subsequently fuse. The insights gained will form the basis for our ultimate vision: to reconstitute a functional ‘fertilization interface’ in vitro, and by these means understand one of the most fundamental processes of life.
Financiële details & Tijdlijn
Financiële details
| Subsidiebedrag | € 2.000.000 |
| Totale projectbegroting | € 2.000.000 |
Tijdlijn
| Startdatum | 1-1-2023 |
| Einddatum | 31-12-2027 |
| Subsidiejaar | 2023 |
Partners & Locaties
Projectpartners
- FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE GESELLSCHAFT MBHpenvoerder
Land(en)
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Shaping the future – From spermatids to spermatozoa
The project aims to enhance understanding of sperm cell morphology and motility through advanced imaging techniques, with implications for infertility diagnosis and potential male contraceptive development.
A Newly Identified Cilium in Meiosis - Deciphering the Principles and Mechanisms of the Zygotene Cilium
ZygoCiliaAct aims to uncover the role of the zygotene cilium in meiosis, linking chromosomal pairing to cytoplasmic mechanisms, and advancing understanding of fertility and ciliopathies.
Self-sabotage in the early mammalian embryo: investigating the interplay between DNA damage responses, splicing failure and zygotic reprogramming
This project aims to investigate the roles of DNA damage response pathways and splicing failures in early mouse embryo development and totipotency through a multidisciplinary approach.
Coupling morphogen dynamics with mechanics in the control of form and pattern
This project aims to uncover how morphogen dynamics and mechanical properties interact to coordinate patterning and morphogenesis in zebrafish and human gastruloids, with broader implications for biology and medicine.
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This project aims to unravel the gene regulatory networks of mammalian sex determination using advanced techniques to enhance understanding of gonad development and related disorders.
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Spermotile aims to revolutionize male infertility treatment by providing an automated, AI-driven sperm selection platform that enhances ART success rates and reduces costs for clinics and patients.