Multiscale Modelling Group of Biological Systems
Scientic Supervisor / Contact Person
Name and Surname
Jorge R. Espinosa
ORCID (link)
Localization & Research Area
Faculty / Institute
Faculty of Chemical Science
Department
Physical Chemistry
Research Area
Chemistry (CHE)
MSCA & ERC experience
Research group / research team hosted any MSCA fellow?
No
Research group / research team have any ERC beneficiaries?
Yes
Research Team & Research Topic
Research Team / Research Group Name (if any)
Multiscale Modelling Group of Biological Systems
Brief description of the Research Team / Research Group / Department
Our group is focused on elucidating the molecular mechanisms and thermodynamic driving forces behind physiological and pathological phase transitions of protein complexes, nucleic acids and chromatin. Through multiscale molecular dynamics simulations at different resolution-levels, we work on developing novel strategies to prevent aberrant phase transitions in biomolecular condensates caused by protein misfolding and changes in the environmental conditions. We combine expertise in atomistic and coarse-grained modelling, bioinformatics, machine-learning approaches, and advanced sampling simulation techniques. The group is funded by an AEI Spanish National Grant (Generación de Conocimiento 2022), an ERC Starting Grant (2024), EPSRC (UK scientific council) and RES (Spanish research council) grants for High-Performance Computing (HPC) resources (2024-2025), and several consultancy contracts with BAYER Ltd. Our group led by Dr. Espinosa currently comprises 3 Postdocs, 4 PhD students, and 3 undergraduate and Master students. As a computational group, we are building a High-Performance Computational facility equipped with 15 high-performance servers (AMD) with 96 CPU cores per server and 2 additional high-performance servers with 48 CPU cores and 2 NVIDIA L40S EDU GPUs with 18.176 CUDA cores per server. In total, our HPC center has 1632 CPU cores.
Research lines / projects proposed
The spatiotemporal organisation of the cell material represents one of the great wonders in physics, chemistry and biology. Compartmentalisation plays a key role in such precise molecular coordination and enables cellular function. Over the past decade, transformative experiments have revealed that most intracellular compartments are not enclosed by membranes, but instead they are dynamical assemblies, termed condensates, and thought to occur via liquid-liquid phase separation of biomolecules. Nevertheless, the dysregulation of these condensates—mostly formed by proteins and nucleic acids—can give rise to deleterious solid-like aggregates, which are associated with the proliferation of age-related and neurodegenerative disorders.
Our project aims to develop an innovative computational approach to resolve the dynamical behaviour of molecules inside functional condensates that drift their complex physicochemical behaviour into pathological solid aggregates. To this end, we plan to develop a multiscale modelling platform— combining coarse-grained force fields and atomistic simulations—which will address the following critical questions: What are the encoded molecular features in RNA and protein sequences regulating phase behaviour? What pushes biomolecular condensates to shift their material properties over time? Can we prevent the proliferation of pathological aggregates induced by condensate misregulation? The overarching goals of this project are: (1) to understand the thermodynamic and intermolecular forces driving condensates out-of-function; and (2) devise potential strategies for preventing RNA/protein aberrant phase transitions in biomolecular condensates. This project aims to reveal the underlying mechanisms and interactions by which the structure and sequence of RNAs and proteins dictate the material properties of intracellular condensates, and their implication in cellular dysfunction, health and disease.
Our project aims to develop an innovative computational approach to resolve the dynamical behaviour of molecules inside functional condensates that drift their complex physicochemical behaviour into pathological solid aggregates. To this end, we plan to develop a multiscale modelling platform— combining coarse-grained force fields and atomistic simulations—which will address the following critical questions: What are the encoded molecular features in RNA and protein sequences regulating phase behaviour? What pushes biomolecular condensates to shift their material properties over time? Can we prevent the proliferation of pathological aggregates induced by condensate misregulation? The overarching goals of this project are: (1) to understand the thermodynamic and intermolecular forces driving condensates out-of-function; and (2) devise potential strategies for preventing RNA/protein aberrant phase transitions in biomolecular condensates. This project aims to reveal the underlying mechanisms and interactions by which the structure and sequence of RNAs and proteins dictate the material properties of intracellular condensates, and their implication in cellular dysfunction, health and disease.
Key words
Application requirements
Professional Experience & Documents
The candidates must submit: (1) motivation letter, (2) curriculum vitae, (3) list of publications, and (4) 1-page summary of the specific project they would like to perform.
One Page Proposal
You can attach the 'One Page Proposal' to enhance the attractiveness of your application. Supervisors usually appreciate it. Please take into account your background and the information provided in Research Team & Research Topic section to fill in it.
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