Main Research Areas: Organic Chemistry; Chemical Biology; Computational Biochemistry
PI: Giorgio Colombo
ERC Sectors: PE5_17 Organic chemistry; PE5_11 Biological chemistry; LS1_1 Macromolecular complexes including interactions involving nucleic acids, proteins, lipids and carbohydrates; LS1_14 Innovative methods and modelling in molecular, structural and synthetic biology
Our research aims to explore the links between protein sequence, structure, conformational dynamics and molecular recognition to identify the atomistic determinants of defined biological (mis)functions. These objectives are pursued through a combination of existing and newly developed computational and theoretical techniques. Insights gained from these studies are used to define new principles for rational protein-design, drug-design and binding epitope prediction. Specifically, the main goals of my research are:
1) to integrate molecular dynamics, computational physical-chemistry and bioinformatics approaches to study the dynamics and specificity of protein-ligand recognition and binding;
2) to translate this information into the rational design of new molecules taking the full flexibility of the receptor and the ligand into account;
3) to develop computational methods to understand the determinants of protein-antibody and protein-protein interactions with the aim to design novel immunoreactive molecules. The strength of our research relies on the strong integration with collaborative experimental approaches to provide valuable mechanistic interpretations and validations of our theoretical predictions. Our main collaborations entail links with: 1) X-ray and NMR groups to validate computational predictions from the structural and dynamical points of view; 2) Molecular immunology groups to test the vaccinological potential of our epitope predictions and new antigen designs; 3) Chemical and molecular biology groups with the aim to test in vitro and in vivo the activities of rationally designed molecules and protein modifications.
University of California San Francisco (Dr. David A. Agard; Dr. Jason E. Gestwicki),
SUNY Upstate Medical University (Dr. Mehdi Mollapour),
Istituto Nazionale dei Tumori Milano (Dr. Nadia Zaffaroni),
Istituto di Ricerche Farmacologiche Mario Negri (Dr. Giulia Taraboletti)
Gonzalez-Teran, B.; Colombo, G.; Conklin, B.R.; Black, B.L.; Bruneau, B.G.; Krogan, N.J.; Pollard, K.S.; Srivastava, D.
Transcription factor protein interactomes reveal genetic determinants in heart disease.
Cell 2022, S0092-8674(22)00079-4
Serapian, S. A.; Moroni, E.; Ferraro, M.; Colombo, G.
Atomistic Simulations of the Mechanisms of the Poorly Catalytic Mitochondrial Chaperone Trap1: Insights into the Effects of Structural Asymmetry on Reactivity.
ACS Catalysis 2021, 11 (14), 8605-8620.
Sanchez-Martin, C.; Moroni, E.; Ferraro, M.; Laquatra, C.; Cannino, G.; Masgras, I.; Negro, A.; Quadrelli, P.; Rasola, A.; Colombo, G.,
Rational Design of Allosteric and Selective Inhibitors of the Molecular Chaperone TRAP1.
Cell Reports 2020, 31 (3), 107531.
Serapian, S. A.; Marchetti, F.; Triveri, A.; Morra, G.; Meli, M.; Moroni, E.; Sautto, G. A.; Rasola, A.; Colombo, G.
The Answer Lies in the Energy: How Simple Atomistic Molecular Dynamics Simulations May Hold the Key to Epitope Prediction on the Fully Glycosylated SARS-CoV-2 Spike Protein.
The Journal of Physical Chemistry Letters 2020, 8084-8093.
Paladino, A.; Woodford, M. R.; Backe, S. J.; Sager, R. A.; Kancherla, P.; Daneshvar, M. A.; Chen, V. Z.; Bourboulia, D.; Ahanin, E. F.; Prodromou, C.; Bergamaschi, G.; Strada, A.; Cretich, M.; Gori, A.; Veronesi, M.; Bandiera, T.; Vanna, R.; Bratslavsky, G.; Serapian, S. A.; Mollapour, M.; Colombo, G.
Chemical Perturbation of Oncogenic Protein Folding: from the Prediction of Locally Unstable Structures to the Design of Disruptors of Hsp90–Client Interactions.
Chemistry – A European Journal 2020, 26 (43), 9459-9465.
Title of the project: Integrative approaches to target Hsp90 complexes in cancer.
Funding Organization: Italian Association for Cancer Research (AIRC)
Duration: 2018-2022
Role in the project: Principal Investigator.
Funding received: 495000€
Contract number: IG20019
Title of the project: Identifying and targeting metabolic liabilities in the crosstalk between childhood B-cell lymphomas and their microenvironment.
Funding Organization: IRP
Duration: 2021-2024
Role in the project: Co-PI.
Funding received: 60000€
Title of the project: BRAVE - Protecting the brain from COVID-19-mediated neurodegeneration through inflammasome inhibition
Funding Organization: European Commission – Human Brain Project P1-EBRAINS
Duration: 2021-2023
Role in the project: Co-PI.
Funding received: 112500€
Title of the project: TRAPping tumor growth: designing molecules to perturb the chaperone TRAP1, from enzymatic activities to cell-cell interaction.
Funding Organization: Miur
Duration: 2022-2025
Role in the project: PI.
Funding received: 662400€ - 247458€
Title of the project: KC210150 – “Targeting the Chaperone-Mediated Folding of CDK4 in Kidney Cancer
Funding Organization: Department of the Army, US ARMY MEDICAL RESEARCH ACQUISITION ACTIVITY
Duration: 2022-2023
Role in the project: PI.
Funding received: 65000USD