Dynamics of biological processes

Dynamics of biological processes

Gustavo Fuertes Vives

Gustavo Fuertes Vives — Project head

About us

The aim of this Project is to understand how light controls the structure, dynamics and activity of photosensitive proteins.

Mission and vision

The aim of this Project is to understand how light controls the structure, dynamics and activity of photosensitive proteins. We focus on transcription factors that interact with specific sequences of DNA in a light-dependent manner (EL222, CarH, CooA). Photon absorption by the embedded chromophores triggers conformational changes in the protein chain that ultimately alter protein-protein and protein-DNA interaction networks in the cell. Our plan is to unveil the molecular details of photoswitching between “dark” and “light” states on time scales ranging from femtoseconds to hours. The acquired knowledge will allow us to create novel photoreceptors for use in areas like synthetic biology, photopharmacology and optogenetics.

Methods

We employ an integrative 4D structural biology approach combining methods with distinct spatial and temporal resolution:

  • Molecular biology:
    • Molecular cloning, protein production & engineering. 
    • Site-specific isotopic labeling (SSIL).
    • Genetic code expansion (GCE) technology to incorporate non-canonical amino acids.
  • Steady-state and time-resolved biophysical methods:
    • Femtosecond-stimulated Raman spectroscopy (FSRS).
    • 1D and 2D-infrared spectroscopy (2D-IR).
    • Fluorescence spectroscopy (FRET, FCS and FA).
    • Small-angle neutron (SANS) and X-ray scattering (SAXS).
  • Computational methods:
    • Density functional theory (DFT).
    • Quantum mechanics/ molecular mechanics (QM/MM).
    • Molecular dynamics (MD).

Objectives

  • Molecular basis of photocontrolled protein-protein and protein-DNA interactions.
  • Development of GCE technology for the site-specific labeling of proteins.
  • Analysis of photoinduced processes in biomolecules using advanced computational tools.
  • Elucidation of vibrational energy transfer pathways in biomolecules.

News

Publications

2020

Andrikopoulos P. C.; Liu Y.; Picchiotti A.; Lenngren N.; Kloz M.; Chaudhari A. S.; Precek M.; Rebarz M.; Andreasson J.; Hajdu J.; Schneider B.; Fuertes G.; Femtosecond-to-Nanosecond Dynamics of Flavin Mononucleotide Monitored by Stimulated Raman Spectroscopy and Simulations, PCCP 2020, https://doi.org/10.1039/C9CP04918E

2019

Fuertes, G., Nevola, L., and Esteban-Martin, S. (2019). Perspectives on drug discovery strategies based on IDPs in Intrinsically Disordered Proteins: Dynamics, Binding, and Function, Academic Press, pp. 275-327. https://doi.org/10.1016/B978-0-12-816348-1.00009-0

2018

Fuertes, G., Banterle, N., Ruff, K.M., Chowdhury, A., Pappu, R.V., Svergun, D.I., and Lemke,E.A (2018). Comment on “Innovative scattering analysis shows that hydrophobic disordered proteins are expanded in water.” Science 361 (6405). https://doi.org/10.1126/science.aau8230

2017

Fuertes, G., Banterle, N., Ruff, K.M., Chowdhury, A., Mercadante, D., Koehler, C., et al. (2017). Decoupling of size and shape fluctuations in heteropolymeric sequences reconciles discrepancies in SAXS vs. FRET measurements. Proc. Natl. Acad. Sci. 114, E6342–E6351. https://doi.org/10.1073/pnas.1704692114

Team

Gustavo Fuertes Vives Gustavo Fuertes Vives

Gustavo Fuertes Vives

Junior Researcher and Head of Program “Dynamics of Biological Processes”

gustavo.fuertes@ibt.cas.cz
+420325873739
doc. Ing. Bohdan Schneider, CSc., DSc doc. Ing. Bohdan Schneider, CSc., DSc

doc. Ing.
Bohdan Schneider, CSc., DSc

Head of Structural Biology and Protein Engineering Program, Head of the Intermolecular Recognition of Proteins and Nucleic Acids Group

bohdan.schneider@ibt.cas.cz
+420325873701

Teaching

Are you interested in working on a project to gain molecular insights into the biology of photoactive proteins?

Currently, there are opportunities to join our team as a PhD student, Master's student or Bachelor's. Students will have the opportunity to work on multidisciplinary projects and to train in wet and dry lab approaches to study light-induced phenomena in biomolecules like electron/proton/energy transfer, conformational changes, folding transitions, allosterism and hierarchical assembly. Students are expected to be highly motivated to work on challenging research questions in an international team and collaborative environment.

Please contact Gustavo Fuertes to discuss your project ideas. Applicants are encouraged to get in touch with additional suggestions of project directions.

Alumni

thesis author thesis name thesis type term
Catarina Alexandra Oliveira Domingos Photobiology of light-sensitive transcription factors Master 03-07/2019
Natalie Huhn Photobiology of the "non-canonical" DNA-binding EL222 protein Internship (DAAD Rise Worldwide) 08-09/2019

Offered topics

thesis author thesis name thesis type
Aditya Suresh Chaudhari Structural dynamics of the light-sensitive transcription factor EL222 PhD (IN PROGRESS)
Theresa Heinrich 4D structural biology of the light-activated DNA-binding protein EL222 Internship (DAAD Rise Worldwide) CANCELLED DUE TO COVID-19
Electronic structure calculations and spectroscopy of biologically relevant chromophores Research internship
Gina Göritz Erasmus+ internship
Edel Cunill Semanat Monitoring light-induced biological phenomena by advanced optical microscopy methods Visiting scholar
Photobiology of the B12-based transcription factor CarH Research internship
A database of non-canonical amino acids Research internship

Collaboration

BIOCEV

This Project has a close collaboration with the “Intermolecular Recognition of Proteins and Nucleic Acids” Project and the “Structure of Medically and Biotechnologically Important Enzymes” Project. We make extensive use of in-house facilities like the Center of Molecular Structure, the Imaging Methods Core Facility and the Service Technology Laboratory.

Czech Republic.

Together with the ELI Beamlines laser facility (Institute of Physics CAS, Dolni Brezany), we are part of the ELIBIO (Structural Dynamics of Biomolecular Systems) Project led by Janos Hajdu. The ELIBIO team explores new frontiers in light and optics to create breakthrough science in biology, chemistry and physics.

Overseas.

Our group has access to large-scale research infrastructures to perform cutting-edge experiments including SANS (Institute Laue Langevin, France), SAXS (the European Molecular Biology Laboratory, Germany) and time-resolved spectroscopy (LaserLab Amsterdam, The Netherlands). We have exciting collaborations with research groups worldwide: