Objective
Intrinsically Disordered Proteins (IDPs) are characterized by their inability to spontaneously fold into a defined 3D structure. Nonetheless, many IDPs are able to undergo disorder-to-order transitions upon binding to interaction partners, in a process known as coupled folding and binding. Although different mechanisms have attempted to rationalize this process, technical limitations have prevented from deciphering the underlying principles of coupled folding and binding.
Here, I will tackle this biological problem by introducing a novel, highly interdisciplinary approach integrating, for the first time, optical tweezers (OT) and single-molecule FRET (smFRET) to resolve the microscopic steps in coupled folding and binding; and Ancestral Sequence Reconstruction (ASR) as a rational strategy to guide protein engineering.
For this purpose, I will study the nuclear co-activator binding domain (NCBD) and its multiple polypeptide binding partners (both intrinsically disordered and structured) as a model to resurrect, using customized ASR methods, the sequences of interacting pairs at multiple divergence nodes along a wide evolutionary scale. Then, I will characterize their intermolecular binding and intramolecular conformational dynamics with OT/smFRET.
This cutting-edge project will result in the determination of mutational trajectories defining i) the emergence of coupled folding and binding, ii) the evolution of this process, and iii) the impact of promiscuous binding to multiple partners on its evolution. This data will allow to extract the essential determinants of coupled folding and binding.
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.
You need to log in or register to use this function
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.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
See all projects funded under this programme -
H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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.
MSCA-IF-EF-ST - Standard EF
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) H2020-MSCA-IF-2017
See all projects funded under this callCoordinator
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.
8006 Zurich
Switzerland
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.