Objective
Protein synthesis and degradation, energy metabolism, signalling, processing of information-encoding polymers (RNA and DNA) are facilitated and regulated by molecular machines, protein complexes that undergo significant conformational changes in time as they facilitate their function. To be able to control the biological processes rationally and with high precision it is essential to understand their mechanism at atomic level. A powerful way to gain detailed insight onto function of these proteins is to see these molecules at atomic resolution while they function. The high-resolution structures of biological macromolecules obtained by X-ray crystallography, NMR and more recently single particle electron cryogenic microscopy (cryo-EM) have provided insights onto the way many molecular machines are constructed. These methods generally provide snapshots of discrete long-lived states, visualizing the conformational changes along the reaction trajectory at high-resolution often remains an elusive objective.
The aim of my proposal is to develop methods for visualizing transient conformations of protein complexes by time-resolved single particle cryo-EM. Time-resolved cryo-EM combines structural study with kinetics by freeze-trapping kinetic intermediates in a biological reaction and has potential to provide atomic-resolution ‘movies’ of functioning biological complexes. Technical limitations however so far restricted widespread use and utilization of the complete potential of this technique.
Main part of this project is dedicated to development of microfluidic instruments for cryo-EM sample preparation. If successful, our approaches will allow trapping kinetic intermediates of molecular machines with millisecond time-resolution using picogram amounts of protein sample. The developed method will be applied to resolve key functional conformations of respiratory complex I and observe regulatory trajectories of ligand-gated ion channels.
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 biological sciences genetics DNA
- natural sciences earth and related environmental sciences geology mineralogy crystallography
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences physical sciences optics microscopy
- natural sciences biological sciences genetics RNA
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.
Keywords
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)
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-2016-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.
9052 ZWIJNAARDE - GENT
Belgium
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.