Objective
Proteins hosting regions highly enriched in one or few amino acids, the so-called Low-Complexity Regions (LCR), are very common in eukaryotes and play crucial roles in biology. Homorepeats, a subfamily of LCR that present stretches of the same amino acid, perform very specialized functions facilitated by the localized enrichment of the same physicochemical property. In contrast, numerous severe pathologies have been associated to abnormally long repetitions. Despite the relevance of homorepeats, their high-resolution characterization by traditional structural biology techniques is hampered by the degeneracy of the amino acid environments and their intrinsic flexibility. In chemREPEAT, I will develop strategies to incorporate isotopically labelled and unnatural amino acids at specific positions within homorepeats that will overcome present limitations. These labelled positions will be unique probes to investigate for first time the structure and dynamics of homorepeats at atomic level using complementary biophysical techniques. Computational tools will be specifically developed to derive three-dimensional conformational ensembles of homorepeats by synergistically integrating experimental data.
chemREPEAT strategies will be developed on huntingtin (Htt), the prototype of repetitive protein. Htt hosts a glutamine tract that is linked with Huntington’s disease (HD), a deadly neuropathology appearing in individuals with more than 35 consecutive Glutamine residues that represent a pathological threshold. The application of the developed approaches to several Htt constructions with different number of Glutamines will reveal the structural bases of the pathological threshold in HD and the role played by the regions flanking the Glutamine tract.
The strategies designed in chemREPEAT will expand present frontiers of structural biology to unveil the structure/function relationships for LCRs. This capacity will pave the way for a rational intervention in associated diseases.
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.
- natural sciences earth and related environmental sciences geology mineralogy crystallography
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine pathology
- natural sciences chemical sciences organic chemistry amines
- natural sciences biological sciences molecular biology structural biology
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
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.
-
H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
See all projects funded under this programme
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.
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.
ERC-COG - Consolidator Grant
See all projects funded under this funding scheme
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2014-CoG
See all projects funded under this callHost institution
Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
75654 PARIS
France
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.