Initially funded by the European Commission’s Horizon 2020 programme, the first four ENABLE conferences were held in the cities hosting the headquarters of the four entities leading the project: the Institute for Research in Biomedicine (IRB Barcelona) in Barcelona, Spain; the Radboud Institute for Molecular Life Sciences (RIMLS) in Nijmegen, The Netherlands; The Novo Nordisk Foundation Center for Protein Research (CPR) in Copenhagen, Denmark; and the Scuola Europea di Medicina Molecolare (SEMM), in Milan, Italy.
In this new cycle of conferences, FEBS, IUBMB and the four core ENABLE institutions have joined forces to share ENABLE best practices with other international research institutions. To this end, in addition to the four core research centres, other institutions can apply to become associated centres and host one of the events. For the 2024 event, FEBS-IUBMB-ENABLE will actively search for an associated centre in a non-European country to ensure that one of the events is held on another continent.
Thaís Cristtina Neves Martins
Biochemistry / PhD student, Federal University of Rio de Janeiro
Rohit Pappu
Gene K. Beare Distinguished Professor of Engineering in the Department of Biomedical Engineering, Washington University in St. Louis
ACTIVE RESEARCH PROGRAM
Cellular Organization Molecular Biophysics & Bioengineering
Our research is focused on uncovering the biophysical principles underlying the spatial and temporal organization of cellular matter, its impact on cell physiology and disease, and leveraging fundamental insights for designing novel materials and biomolecular condensates. Our investigations span multiple length scales and involve a collective effort on the biophysical principles pertaining to the form, function, regulation, phase behavior, and evolution of intrinsically disordered proteins, multivalent proteins, and RNA molecules. Our research directly impacts topics of biomedical relevance that include the molecular basis of neurodegeneration, phase transitions that lead to protein and RNA condensates, the biophysics of molecular recognition via soft and disordered interfaces, and the design of responsive, protein-based biomaterials. Our work is driven by a blend of novel multiscale computer simulations, adaptations and developments of polymer physics theories, the physics of active matter and non-equilibrium statistical physics of living systems. We close the loop with in vitro and in cell experiments performed in my lab and through a vibrant network of international collaborations.
Intrinsically disordered proteins (IDPs): Over the years, we have uncovered sequence-ensemble relationships of IDPs that connect the information encoded in amino acid sequences to quantitative descriptions of conformational ensembles. These efforts have yielded predictive descriptions and uncovered the rich contributions made by amino acid composition, charge content, and sequence patterning effects to the global sizes, shapes, amplitudes of conformational fluctuations, and context dependent secondary structural preferences within IDPs / IDRs. These discoveries have been made possible through novel combinations of polymer physics theories, accurate and efficient molecular simulations driven by our homegrown ABSINTH implicit solvation model, and biophysical experiments. In ongoing investigations, we are pursuing three new avenues: (1) We are using computationally driven approaches to design novel IDPs / IDRs with bespoke sequence-ensemble relationships to uncover the connections between these relationships and molecular functions. (2) We are developing and deploying new, multiscale computational and theoretical approaches to model circuits controlled by multisite phosphorylation and other multisite post-translational modifications within IDPs. (3) We are deploying new methods to investigate the effects of sequence-specific charge regulation, specifically proton uptake and release phenomena on disorder-order transitions of IDPs / IDRs in cellular milieus. These efforts have led to the development of a novel q-canonical ensemble for describing conformational and proton binding equilibria. Importantly, our development and deployment of the q-canonical formalism has paved the way for decoupling measurements of charge from measurements of conformation, thereby allowing us to use these independent measurements and the information they provide as restraints for atomistic simulations. Our approaches are yielding surprising findings regarding the diversity of charge and conformational states that are operative in the functions of IDPs. (4) Bacterial IDPs are hypervariable and yet they play decisive roles in bacterial life cycles. We are combining multilevel theory, computation, biochemical experiments, and high-throughput library-based in vivo investigations to make headway into the design of bacterial communities with bespoke emergent properties and the selective inhibition of bacteria by targeting IDPs using novel antibiotics.
Phase transitions in cell biology: We are actively working on the problem of phase transitions that are controlled or influenced by multivalent proteins and RNA molecules. These phase transitions include sol-gel transitions as well as liquid-liquid, liquid-solid, and liquid-liquid crystalline phase separation. Our focus is on describing relationships between protein sequences / architectures and the stimulus specific phase diagrams that are governed by spontaneous driving forces also known as passive processes. This focus is driven by the importance of biomolecular condensates that form via phase transitions afford spatiotemporal organization and information transduction within cells. Specific foci include nuclear bodies, stress responses, synaptic bodies, and the interplay between spontaneous and driven processes. The unique approach we are pursuing is based on adaptations of the physics of associative polymers, specifically the stickers-and-spacers framework, and introduction of the concept of phase separation++ i.e., accounting for density transitions along with geometric transitions, and symmetry breaking.
The physics of coarse graining: Collective phenomena and collective properties are the defining hallmarks of living systems. For example, properties such as interfacial tension or interfacial energies of biomolecular condensates arise from the collective properties of solvent, solutes, and macromolecules and asymmetries of these properties across phase boundaries. Defining, measuring, and interpreting collective properties requires the identification of collective coordinates, and this requires a systematic, bottom-up coarse-graining approach. Our methods, inspired by the force-matching approach of the Voth group, and anchored in the tenets of renormalization group theories, are enabling the development of novel, system or architecture-specific coarse-grained models that have enabled the discoveries and demonstrations of key conceptual aspects of phase separation++. A key advancement has been the development of a lattice-based engine known as LaSSI that affords the promise of being able to adapt the physics of RG theory to identify flows in interaction space.
Neurodegeneration: We work on connecting the driving forces for and the mechanisms of polyglutamine aggregation and phase separation to intracellular interactions that lead to neurodegeneration in HD and other polyglutamine expansion disorders. An emerging focus is on the modulation of aggregation and phase behavior by endogeneous networks of protein-protein interactions.
Molecular and Cellular Engineering: We are building on our work pertaining to phase transitions and IDPs to develop, prototype, and deploy computational methods to predict phase behavior from amino acid sequence and advance the design of responsive peptide and protein-based biomaterials. Our design approaches are based on supervised machine learning and adaptation of genetic as well as evolutionary algorithms. Through these efforts, we are expanding the universe of IDPs that demonstrate stimulus responsive phase behaviors.
I am currently a PhD student in Medical Biochemistry. My research focuses on cervical cancer progression and seminal fluid factors.