Grégoire Courtine and Oliver Hantschel win ERC grants
Grégoire Courtine and Oliver Hantschel © Hillary Sanctuary/Oliver Hantschel - EPFL
Professors Grégoire Courtine and Oliver Hantschel have been awarded ERC Consolidator Grants.
The European Research Council’s (ERC) Consolidator Grants are given annually to researchers of any nationality with 7-12 years of research experience after completion of their PhD, as well as “a scientific track record showing scientific talent and an excellent research proposal”.
The Consolidator Grants, which generally provide funding for 5 years, are part of the ERC’s commitment to support “the highest quality research in Europe with competition-based financing”, with the ultimate aim “to establish and solidify European research as cutting-edge research.”
The 2015 ERC Consolidator grants amounted to €585 million awarded to a total of 302 mid-career scientists of 34 different nationalities. EPFL was represented by six winners, two of which are from the School of Life Sciences: Grégoire Courtine and Oliver Hantschel.
Grégoire Courtine: Mechanisms of recovery after severe spinal cord injury
Professor Courtine’s proposal aims to identify the circuit-level remodeling, computational principles, and molecular cues that govern the immediate and long-term recovery of motor functions following spinal cord injury. In their previous research, funded by an ERC Starting Grant, Courtine’s group at EPFL developed a “pragmatic therapy” that restored supraspinal control of leg movement after complete paralysis in rats.
The therapy, named “neuroprosthetic rehabilitation”, acts over two time windows: an immediate electrical and chemical spinal cord stimulation that mediates motor control of the animal’s paralyzed hind limbs, followed by long-term will-powered training regimens enabled by electrochemical stimulation and robotic assistance promote neuroplasticity of residual connections. This results in extensive rewiring that reestablishes voluntary movement in the animal.
Building on this system, Courtine’s group will now use their unique neuroprosthetic platform and next- generation experimental techniques to carry out longitudinal assessment of neuroplasticity and function in freely behaving mice. The reason for this is that there exists a knowledge gap about the mechanisms that underlie the effects of neuroprosthetic rehabilitation, which currently represents an empirical approach. In order to convert it to an evidence-based strategy with clinical perspectives, it is critical that the knowledge gap is filled.
The new proposal will do this by establishing causality between the reorganization of the animal’s motor circuitry and its functional recovery. In this framework, Courtine’s group will combine optogenetics, circuit-level inactivation techniques, unconstrained chronic calcium imaging, virus-mediated tract-tracing and genetic manipulations.
The ERC proposal states: “This project will fertilize frontier research with new knowledge and ideas, ultimately accelerating clinical implementation of safer and more efficacious therapies to improve the quality of life for spinal cord injured individuals.”
Oliver Hantschel: Targeting common oncogenes with intracellular monobodies
Professor Hantschel’s proposal aims to develop small engineered antibody mimics, called monobodies, against ten key intracellular oncoproteins for which no chemical inhibitors exist, and to test the activity of the monobodies in cancer cells. The ultimate goal is to establish monobodies as a novel class of intracellular protein-based therapeutics, and turn them from basic research tools into therapeutic applications in cancer patients.
Because of their remarkable plasticity, oncogenic signaling networks can quickly become resistant to most targeted therapeutics, such as monoclonal antibodies and small-molecule kinase inhibitors. Even though alterations in oncogenes and tumor-suppressor genes are relatively few, these approaches often fail to significantly improve the survival of cancer patients. And despite the rising numbers of targeted drugs already in clinical use, they inhibit only a very limited number of protein targets – mostly kinases. As a result, most intracellular non-kinase oncoproteins remain untargeted.
Hantschel’s previous research has established monobodies as potent and specific enough to target intracellular protein-protein interactions that are mediated by the SH2 domains of certain oncogenic kinases and phosphatases. His work showed that expressing SH2-targeting monobodies inhibits both the signaling and oncogenetic properties of oncoproteins.
Following on this, Hantschel now wants to achieve a “clinical translation” of monobody-based therapeutics. To do this his group will develop methods of delivering monobody proteins into cancer cells, followed by mouse cancer models.
Hantschel’s proposal also plans to develop and test “mirror-image” monobodies, which are composed of D-amino acids. The idea is to use them to increase intracellular and plasma stability, and limit immunogenicity.
The proposal states: “This innovative endeavor uses state-of-the-art protein engineering techniques to address a central problem in cancer medicine and may provide a groundbreaking new approach to target cancer.”