A versatile new approach to seek constitutive or conditional helicase substrates at global scale

Helicases are ubiquitous ‘molecular motor’ enzymes that disrupt nucleic acid (NA) helices and NA-protein interactions. Despite the key roles of helicases in many cellular processes and diseases, their target repertoires and the determinants of their functional specialization are often unknown. Scientists from the ‘RNA remodeling’ group of CBM have developed a new screening scheme, Helicase-SELEX, to elucidate helicase substrate requirements and find natural or synthetic helicase substrates in large NA sequence libraries. Using the transcription termination Rho helicase as prototype, the CBM scientists have discovered ~3300 functional substrate sequences in Escherichia coli, thereby providing the first detailed map of Rho utilization (Rut) sites at genome scale. Further, they have shown that inclusion of a Rho cofactor (NusG) in the selection scheme can modulate the H-SELEX outcome and help probe specificity determinants at global scale. Finally, they have used H-SELEX to evolve synthetic Rut sequences operating as riboswitches able to elicit Rho activity in vitro and in vivo only in presence of an orthogonal cofactor (serotonin). Thus, Helicase-SELEX is a versatile new approach to characterize or exploit helicases for fundamental or biotechnology purposes.

The CNRS Institute of Chemistry has reported this new original screening approach on its website

Référence

Delaleau M., Eveno E., Simon I., Schwartz A & Boudvillain M.
A scalable framework for the discovery of functional helicase substrates and helicase-driven regulatory switches
PNAS 2022

https://www.pnas.org/doi/10.1073/pnas.2209608119

Eva Jakab Toth receives the “Torsten Almén” Award

Eva Jakab Toth, co-leader of the "Metal complexes and MRI" group, received the "Torsten Almén" Award for her pioneering research on contrast agents, from the "Contrast Media Research" committee of the World Molecular Imaging Society (WMIS).

This biannual prize rewards unique research activities that have shaped the field of contrast agents. Torsten Almén was a pioneer in the field of non-ionic contrast agents for radiography. His work forever revolutionized the research and clinical use of X-ray imaging agents. In the same spirit, the committee specifically identified "the creativity of the preclinical and translational work of Eva Jakab Toth, in the design, deep characterization and application of paramagnetic MRI contrast agents".

Eva Jakab Toth gave the “Torsten Almén Medal Award” lecture at the 2022 « Contrast Media Research » Symposium in Annapolis, Maryland (August 21-25, 2022).

 

Annual scientific day of the Federation of Physics and Life Chemistry Research at the UFR Law, Economics, Management of the University of Orléans.

Guest speakers:

Martin Picard, Laboratory of Physico-Chemical Biology of Membrane Proteins, IBPC, Paris - "Structure-function study of tripartite efflux pumps from Gram negative bacteria in lipid nanodiscs, proteoliposomes, amphipols, or in their native membranes"

Christophe Rochais, director of CERMN, Caen - "Application of the concept of polypharmacology to the design of donecopride, a preclinical candidate against Alzheimer's disease"

Programm

Professor Vincent L. Pecoraro of the University of Michigan is invited at the CBM from May to August 2022 through a LE STUDIUM Research Professorship

Professor Pecoraro is internationally recognized for his major contributions in bioinorganic chemistry, notably on the role of manganese complexes and clusters in photosynthetic water oxidation. He is also a pioneer in the design of metalloenzyme mimetics and in the study of metallacrown complexes with unique magnetic and/or luminescence properties for developments in medical imaging, a field in which several patents have recently been filed with the team “Luminescent lanthanide compounds, optical spectroscopy and bioimaging” from the CBM.

Professor Pecoraro was awarded the Blaise Pascal International Chair in 2010. In 2021, he received an honorary doctorate from the University of Aix-Marseille and a LE STUDIUM Research Professorship (Loire Valley Institute). In addition, Professor Pecoraro is the 2021 recipient of the Franco-American award from the American Chemical Society and the “Société Chimique de France”.

He is currently president of the Society of Biological Inorganic Chemistry.

He is one of the co-founder of the startup VIEWaves founded in Orléans in March 2022 that aims at the commercialization of the optical imaging agents emitting in the near-Infrared domain created on the basis of the collaborative work conducted with the team at CBM.