Objective
At the dawn of the 21st century, our knowledge of the molecular mechanism of mammalian
fertilization remains very limited. Different lines of evidence indicate that initial gamete recognition
depends on interaction between a few distinct proteins on sperm and ZP3, a major component of the
extracellular coat of oocytes, the zona pellucida (ZP). On the other hand, recent findings suggest an
alternative mechanism in which cleavage of another ZP subunit, ZP2, regulates binding of gametes
by altering the global structure of the ZP. Progress in the field has been hindered by the paucity and
heterogeneity of native egg-sperm recognition proteins, so that novel approaches are needed to
reconcile all available data into a single consistent model of fertilization. Following our recent
determination of the structure of the most conserved domain of sperm receptor ZP3 by X-ray
crystallography, we will conclusively establish the basis of mammalian gamete recognition by
performing structural studies of homogeneous, biologically active recombinant proteins. First, we
will combine crystallographic studies of isolated ZP subunits with electron microscopy analysis of
their filaments to build a structural model of the ZP. Second, structures of key egg-sperm
recognition protein complexes will be determined. Third, we will investigate how proteolysis of
ZP2 triggers overall conformational changes of the ZP upon gamete fusion. Together with
functional analysis of mutant proteins, these studies will provide atomic resolution snapshots of the
most crucial step in the beginning of a new life, directly visualizing molecular determinants
responsible for species-restricted gamete interaction at fertilization. The progressive decrease of
births in the Western world and inadequacy of current contraceptive methods in developing
countries underscore an urgent need for a modern approach to reproductive welfare. This research
will not only shed light on a truly fundamental biological problem, but also constitute a solid
foundation for the reproductive medicine of the future.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciences clinical medicine gynaecology reproductive medicine
- natural sciences earth and related environmental sciences geology mineralogy crystallography
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences physical sciences optics microscopy electron microscopy
- natural sciences mathematics pure mathematics mathematical analysis functional analysis
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
ERC-2010-StG_20091118
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Host institution
171 77 STOCKHOLM
Sweden
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.