Objective
The main goal of this project will be to construct a thermodynamically consistent comprehensive model for biochemical replication using stochastic thermodynamics and control theory.
I will subjugate the process of kinetic proofreading (KPR) to several thermodynamic bounds that have recently been discovered, in order to study the thermodynamic performance of this process. This will be done by considering the process as a chemical reaction network where a sequence of irreversible steps consume energy to increase replication accuracy and are hence bounded by fundamental no-go theorems such as the thermodynamic uncertainty relation (TUR) or the thermodynamic speed limit (TSL). I then investigate how the topology and reaction rates of the KPR network can be optimized with respect to error rate and dissipation by means of machine learning, to deduce how close biological systems operate to these bounds. Subsequently, I will extend the results to the conformational proofreading (CPR) process, where an energy handicap is added to the free energy to increase binding specificity at the expense of binding affinity. The CPR is a proofreading scheme that does not consume energy by burning ATP/GTP, so the entropy production has its origin in the conformational change.
Finally, I test the robustness of the aforementioned KPR and CPR networks. In realistic systems, the kinetic rates can fluctuate as a consequence of e.g. temperature or chemical density variations, which can possibly destabilize the network and lead to more errors in the replication process. This will be done by considering the networks as input-output systems that can be studied by control theory. This provides fundamental bounds such as Bode's sensitivity integral to complement the TUR and TSL.
I expect that the research results will lead to a better understanding of the fundamental limits on error correction in biological systems and will inspire further research in biophysics and structural biology.
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 physical sciences thermodynamics
- natural sciences mathematics pure mathematics topology
- natural sciences biological sciences biophysics
- natural sciences computer and information sciences software software applications simulation software
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.
-
HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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) HORIZON-MSCA-2022-PF-01
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.
1165 KOBENHAVN
Denmark
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.