Project description
Insight into cell guidance in development
During development, cells are guided to their correct location through a diverse network of guidance proteins that include the semaphorin and plexin families. Although we have a good understanding of the architecture and interactions that trigger semaphorin–plexin signalling, the mechanisms of action of the secreted class 3 semaphorins (Sema3s) remain to be determined. The EU-funded FLEXINGPLEXIN project will focus on the neuropilin co-receptor and its role in semaphorin signalling. The project's findings will impact diverse disciplines beyond basic biology, such as immunology and clinical pathology, and are expected to guide the design of novel therapeutic agents.
Objective
During the development of a multicellular organism cell guidance proteins interact with their cognate cell surface receptors to guide cells to their correct location. Such functions continue to be essential in the adult to maintain tissue homeostasis. Semaphorins use plexins as their main receptors for signalling and the semaphorin and plexin families together constitute one of the largest and functionally diverse of the cell guidance systems in vertebrates. We have gained some insight into the architecture and interactions which trigger semaphorin-plexin signalling, but fundamental questions remain and some of the most puzzling, and of potential clinical importance, concern the mechanisms of action of the secreted class 3 semaphorins (Sema3s), and their (co-)receptors. Neuropilin co-receptors play pivotal roles for Sema3 function and have been implicated in context dependent switching of cell guidance signalling outputs. There is an urgent need for information on molecular mechanism to underpin the design and interpretation of studies into biological function and clinical pathology. To advance the field we will combine structural biology and cellular imaging based approaches with functional studies (in house and in collaboration).
The research plan is sub-divided into three inter-related sections that aim to discover:
1. The structural determinants and mechanisms of action by which class 3 semaphorins exert differing effects on signalling.
2. The conformational state of the plexin ectodomain in different contexts and its contribution to signal outcome.
3. The mechanisms by which neuropilin binding can switch the outcomes of plexin signalling.
Molecular level answers to the questions posed by semaphorin-neuropilin-plexin signalling will take us beyond the current state of the art, and impact on diverse disciplines, for example cellular immunology and developmental biology, as well as guiding the design of novel therapeutic agents.
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: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine immunology
- medical and health sciences basic medicine pathology
- medical and health sciences basic medicine physiology homeostasis
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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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.
Funding Scheme
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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.
ERC-ADG - Advanced Grant
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2019-ADG
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OX1 2JD Oxford
United Kingdom
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