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REPLAY : LENS Webinar #4 on cancer-related research using neutrons, with Gerhard Gröbner and Jean-Michel Jault. 10.09.2020

LENS Webinar #4, Global Health Threats: Cancer-related research using neutrons

This image shows five clinical drugs superimposed in the active site of the human carbonic anhydrase II isoenzyme (hCA II). The image is based on neutron-resolved crystal structures. The active site is flanked by hydrophilic (violet) and hydrophobic (green) binding pockets that can be used to design specific drugs targeting cancer-associated hCAs. ORNL/Andrey Kovalevsky

Gerhard Gröbner: How does the Bcl-2 Protein family regulate apoptosis at the mitochondrial membrane level?

Jean-Michel Jault: Towards the catalytic cycle of a multidrug ABC (“ATP-Binding Cassette”) transporter

10 September 2020, 11:00am CET

Chair: Anne Martel, Institut Laue Langevin

Gerhard Gröbner works at Umeå University in Sweden as biophysical chemist to understand biological membranes, and especially how the function of their proteins is connected to the unique membrane environment. He uses a multidisciplinary biophysical/biochemical approach with focus on NMR methodology and neutron reflectometry to unravel the key structural and functional principles of the Bcl-2 protein family involved in regulation of mitochondrial apoptosis.

The main aim is to determine the membrane-bound structures of the cell-survival Bcl-2 protein itself, its molecular recognition/inhibition of its opposing apoptotic (cancer cell killing) Bax protein and the role of the mitochondrial membrane as an active partner under oxidative apoptotic stress conditions. This way, the research will generate novel molecular knowledge about how these Bcl-2 protein family regulates cell survival versus cell death; knowledge useful in understanding cancer and designing effective tumor therapies.

Jean-Michel Jault is a research director at the CNRS (“Centre National de la Recherche Scientifique”); Director of the UMR5086 CNRS/University of Lyon “Molecular Microbiology and Structural Biochemistry”; Principal investigator of the team “Bacterial nucleotide-binding proteins: resistance to antibiotics and new enzymes”.

Resistance to chemiotherapeutic treatment is an overwhelming problem in health care, not only in cancer therapies but also to eradicate life-threatening micro-organisms. Multidrug efflux transporters play a major role in this phenomenon and in particular some members of the ATP-Binding Cassette (ABC) superfamily. Recent structural advances have considerably increased our understanding of the functioning of these multidrug efflux pumps and I will summarize the current status of the knowledge we have about these pumps, and show how neutron diffraction might help to solve some of the remaining questions.

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