Vladimir Torbeev
Biography
Dr. Torbeev is a professor of biosystems chemistry. In 2021, his group joined the unit Biotechnology and Cell Signalling (BSC), a joint research unit of the French National Centre for Scientific Research (CNRS) and the University of Strasbourg that is located on the premises of the Strasbourg Graduate School of Biotechnology (ESBS).
The research performed by his team combines methods of chemistry and biophysics to study biological problems. The subjects include protein misfolding and aggregation involved in neurodegenerative diseases, new methods of synthesis of protein libraries, approaches to study intrinsically disordered proteins and protein design. The research in the laboratory has been supported by the ATIP-Avenir programme (CNRS-Inserm), the Jean-Marie Lehn Foundation, the ERC Starting Grants programme and the French National Research Agency (ANR).
Vladimir Torbeev received his PhD in chemistry from the University of Chicago (United States) under the direction of Professor Stephen Kent for his work dedicated to total chemical synthesis and biophysical studies of HIV-1 protease. Then, he completed post-doctoral studies in Professor Donald Hilvert’s group at ETH Zurich (Switzerland), working on the molecular mechanism of misfolding and aggregation of β2-microglobulin. In March 2014, he started his independent research group at the Institute of Supramolecular Science and Engineering (ISIS, UMR 7006) and became an associate professor at the University of Strasbourg.
In 2019, Dr. Torbeev was awarded the Guy Ourisson Prize by the Gutenberg Circle. His key achievements from that period are: total chemical synthesis of 24-kDa oligomer mimicking amyloid structure (Chem. Sci. 2018, 9, 5594), development of a “conformational editing” approach to study intrinsically disordered proteins (Chem. Sci. 2021, 12, 1080), and de novo design and synthesis of a protein catalyzing amide bond formation (J. Am. Chem. Soc. 2021, 143, 3330).
Project summary
SUPRAMOLECULAR CONTROL OF PHASE SEPARATION OF INTRINSICALLY DISORDERED PROTEINS
Phase-separation of intrinsically disordered proteins (IDPs) is an example of macromolecular organization resulting in functional membraneless organelles in the cytoplasm and nucleus. It is attracting wide interest due to its involvement in fundamental mechanisms in cell biology and human diseases such as amyotrophic lateral sclerosis (ALS), that currently has no cure.
Unlike well-folded proteins, IDPs are challenging to target and, therefore, new approaches to study IDPs and their phase-separation are needed. Recently, the expression of extended proline-arginine dipeptide repeats in the C9orf72 gene has been identified as a toxic mechanism that affects phase separation of crucial proteins responsible for the ALS disease progression.
This USIAS project aims to obtain fundamental insights into phase separation mediated by proline-arginine repeats relevant to ALS. By using advanced chemical protein synthesis we will prepare the largest possible proline-arginine repeat polypeptides not yet available for characterization.
With the help of various structural and biophysical measurements we expect to gain an understanding of factors resulting in aberrant phase separation in disease and to develop the molecular tools based on principles of supramolecular chemistry to interfere with this phenomenon. The biological relevance of these findings will be evaluated in various cellular assays with the objective of contributing to the future potential therapy against ALS.
Fellowship 2023
Dates - 01/11/2023-31/10/2025
Other information and news (activities, project staff, publications...)
Abhijit Biswas (post-doc) is a chemist by training. During his doctoral degree, he engineered Cell-Penetrating Peptides (CPP) for efficient delivery of siRNA in cancerous cells. After obtaining his PhD in 2021, from Dr. Rituparna Sinha Roy’s laboratory in the Indian Institute of Science Education and Research Kolkata, he received a Mobilitas Pluss postdoctoral grant and joined Professor Margus Pooga’s lab at the University of Tartu (Estonia). There, he learnt the cellular and biological applications of oligonucleotide conjugates of CPP, which allowed him to understand the phenomenon of drug delivery in cancerous cells. Following this first postdoctoral training, he joined Dr. Vladimir Torbeev’s laboratory in the Strasbourg Graduate School of Biotechnology (ESBS) in January 2024 as USIAS postdoctoral researcher.
