HubMOL: Hub Molecules of Metabolism and Signalling – Key regulators of Life
The project Hub Molecules of Metabolism and Signalling – Key regulators of Life, or HubMOL, has been awarded funding to develop therapies for metabolic and regulatory imbalances based on hub molecule biology.
Metabolic disorders are a problem in Europe, putting a major strain on both people's health and the healthcare system. These issues with metabolism can also contribute to other serious diseases like cancer and heart disease.
The root causes of these metabolic problems are many, but they're often linked to unbalanced nutrition. When metabolism goes wrong, it affects how our cells communicate and how our genes are regulated, making the health issues even worse. We still don't fully understand the intricate relationship between metabolism and these other cellular processes.
The HubMol project will explore the dual roles of a set of tiny but essential molecules that are crucial for all cellular functions, which we're calling "Hub Molecules of Life." These include familiar ones like ATP (our body's main energy source) and other crucial cofactors like NAD, FAD, and CoA. These hub molecules are central to both metabolism and cell signalling. For example, they're involved in modifying proteins, a key process that helps cells regulate their functions.
Since maintenance of hub molecules requires the intake of essential nutritional precursors, promising opportunities for therapies, including targeted nutritional supplementation, are theorised. To address the demand for competence in this topical area, HubMOL will train the next generation of specialists in the latest enabling technologies in metabolomics, protein modification analysis and molecular organismal physiology to develop novel hub molecule supplementation strategies and pharmacological approaches targeting hub molecule-dependent signalling and gene regulation. This systems medicine approach will include latest computational modelling approaches thereby further boosting the employability of HubMOL trained researchers as future leaders in clinical nutritional intervention strategies, new biotechnological approaches for and in pharmacological translation, namely, from drug target identification to clinical validation.
Specifically, Simula's role in this project focuses on computational physiology, using advanced computer models to understand how a key molecule, CoA, affects heart function.
Recent research has shown a connection between disorders in CoA synthesis and an increased risk of heart rhythm problems, particularly in patients with a specific genetic mutation. However, we don't yet understand exactly how this deficiency leads to heart rhythm issues.
So, the objectives for Simula are:
- Develop a highly detailed model of cardiomyocyte electrophysiology that includes a detailed representation of energetics and CoA synthesis.
- Elucidate the link between CoA biosynthesis and its role in modifying the cardiac action potential.
- Perform 3D simulations in patient-specific geometries of both healthy and cardiomyopathic hearts to investigate how subcellular changes and geometric abnormalities contribute towards increased propensity towards arrhythmia generation.
Partners
- Universitetet I Tromsø - Norges Arktiske Universitet, coordinator (Norway)
- Universitetet I Bergen (Norway)
- Fundacio Institut de Recerca Contra la Leucemia (Spain)
- Academisch Ziekenhuis Groningen (Netherlands)
- Universitaet Innsbruck (Austria)
- Universitaet Leipzig (Germany)
- Kobenhavns Universitet (Denmark)
- Consiglio Nazionale Delle Ricerche (Italy)
- Universitaetsklinikum Essen (Germany)
- Simula Research Laboratory AS (Norway)
- Mimetas BV (Netherlands)
- MS-omics APS (Denmark)
- Eisbach Bio GmbH (Germany)
Funding
HubMOL is a Marie Skłodowska-Curie Actions Doctoral Network funded by Horizon Europe.
Disclaimer: Funded by the European Union. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or CINEA. Neither the European Union nor the Granting authority can be held responsible for them.
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