Project description
Understanding epidermal growth factor receptor assembly in cancer
The epidermal growth factor receptor (EGFR) regulates cell growth and survival, and its disruption is closely linked to many cancers. The EGFR is known to form oligomers, a process that enhances downstream signalling and response transmission. While the EGFR has been studied for decades, the molecular mechanisms of this oligomerisation remain unexplored. With the support of the Marie Skłodowska-Curie Actions programme, the EGFR_Cryo-ET project will employ cryo-electron tomography (Cryo-ET) to study how EGFR monomers are brought together in dimers and oligomers and to determine their signalling differences. Cryo-ET is a cutting-edge method that enables structural analysis in near-native conditions without altering the structure and function of target proteins. Project findings will provide important insight into EGFR signal properties, guiding future therapies.
Objective
According to the latest estimates from the European Cancer Information System, the incidence and mortality from cancer is projected to increase in the next 20 years. Therefore, there is a strong urge to design safe and effective therapeutic approaches to manage cancer progression and ease the burden of the disease. Although the etiology of cancer is highly complex and multifactorial, disruption of the Epidermal Growth Factor Receptor (EGFR) function is commonly associated with the development of several types of cancers. Despite being in the spotlight since its discovery in the late 70’s, several important aspects of EGFR function (e.g oligomerization and receptor bias) still remain largely unexplored. Inspired by this gap of knowledge, the main aim of this proposal is to shed light into the molecular mechanisms governing EGFR oligomerization and signaling. EGFR in dimeric and oligomeric assemblies will be resolved by Cryo-Electron Tomography (Cryo-ET) in near-native conditions. As substantial differences in the transmission of response between dimer and oligomeric EGFR states can arise (receptor bias), these aspects will also be extensively validated/analyzed in vitro.
Cryo-ET is revolutionizing the field of structural biology, as proteins can now be resolved without laborious purification protocols which potentially alter structure and function of target proteins. Although promising, this technique is still at early stages of development and only large proteins have been successfully resolved. By resolving the structure of a relatively small and flexible protein, the boundaries of this technique would be expanded and be more applicable for the structural characterization of transmembrane receptors. From the biological point of view, knowing the conditions in which EGFR assemblies are formed and that these assemblies have distinct signal properties, specific therapeutic approaches can be designed to treat cancer minimising the occurrence of side effects.
Fields of science (EuroSciVoc)
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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.
- social sciences sociology demography mortality
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences physical sciences optics microscopy electron microscopy
- medical and health sciences clinical medicine oncology
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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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.
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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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2024-PF-01
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13125 Berlin
Germany
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