Project description
Automated modelling platform for dynamically changing biological transport
Computational ‘in silico’ models are increasingly used to understand complex biological systems and accelerate medical research. Ordinary differential equations (ODEs) are a staple of these, yet the best ODEs only model transport in steady state given the intense labour of manual construction. This limits insight into complex dynamically changing transport mechanisms. The ERC-funded AUTOMATHIC project aims to transform this by developing an automated framework combining mathematical modelling and machine learning to identify the appropriate ODE structures, estimate their parameters and efficiently evaluate the resulting models. Focusing on how kidney cells transport toxins and drugs, AUTOMATHIC will use this framework to identify ways to minimise drug toxicity for safer therapies in patients with chronic kidney disease.
Objective
In silico models aim to capture and elucidate the complex and emergent interactions of biological systems, with the goal of expediting research and potential clinical translation. For example, ordinary differential equation (ODE) models of toxin and drug transport are being developed to bring safer therapies to chronic kidney disease patients. Despite recent progress, these cutting-edge ODEs only model transport in steady state and remain limited regarding the amount and complexity of dynamic transport mechanisms as it is often not clear which kinetic relation is most suitable. This limitation is due to the manual and labor-intensive approaches to construct the ODEs, which critically hinder their application in quantitative toxicity assessment in key industrial settings like drug development. In AUTOMATHIC, I will leverage and combine my expertise in mathematical modeling and machine learning to develop an integrated framework for automated ODE structure identification, parameter estimation and model evaluation, focusing on cell transport and signaling, which is the timely leap forward needed to create large dynamic models and transform the field. I will test and illustrate the capabilities of the developed framework by exploring the dynamics and regulation of proximal tubule (PT) toxin and drug transport. I will use the dynamic PT model to define novel therapeutic regimens that minimize toxin accumulation in combination with a state-of-the-art in vitro set-up to measure the essential time series data required for model calibration and validation. The anticipated outcomes of AUTOMATHIC are: 1) a next-generation, integrated framework for automated model structure identification and parameter estimation that will become the new standard for the creation and interrogation of large dynamic models of cell transport and signaling; 2) crucial knowledge about PT transport and metabolism; 3) a dynamic PT model to optimize nephrotoxicity protocols, drug dosing and screening.
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.
This project's classification has been human-validated.
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.
This project's classification has been human-validated.
- natural sciences mathematics pure mathematics mathematical analysis differential equations
- natural sciences computer and information sciences computational science
- natural sciences computer and information sciences artificial intelligence machine learning
- medical and health sciences basic medicine pharmacology and pharmacy
- medical and health sciences clinical medicine nephrology kidney diseases
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.
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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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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.
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-ERC - HORIZON ERC Grants
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2024-STG
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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.
6200 MD Maastricht
Netherlands
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