{"id":4047,"date":"2023-12-04T16:08:28","date_gmt":"2023-12-04T15:08:28","guid":{"rendered":"https:\/\/www.isrec.ch\/?page_id=4047"},"modified":"2025-02-11T14:50:21","modified_gmt":"2025-02-11T13:50:21","slug":"professorial-chairs","status":"publish","type":"page","link":"https:\/\/www.isrec.ch\/en\/the-research\/professorial-chairs\/","title":{"rendered":"Professorial Chairs"},"content":{"rendered":"

Professorships enable young professors affiliated with a Swiss academic institution to launch their research careers.<\/strong><\/p>\n\n\n

Professorships are financed from the Foundation\u2019s assets. The ISREC Foundation assumes the scientific and administrative supervision of the funding, thus guaranteeing the intended use of the allocated funds.<\/p>\n\n\n\n

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Paternot chair for interdisciplinary cancer research – Prof. Nicolas Thom\u00e4 (EPFL)<\/h3>\n <\/div>\n
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Prof. Nicolas Thom\u00e4<\/strong><\/span><\/p>\n

Appointed full professor at EPFL\u2019s Faculty of Life Sciences in September 2023, Prof. Thom\u00e4 comes from the Friedrich Miescher Institute for Biomedical Research in Basel where, since 2006, he led a world-class team of researchers in structural and chemical biology. Prof. Thom\u00e4 is a chemical biologist and expert in X-ray crystallography and cryogenic electron microscopy, two cutting-edge technologies which he uses to study the key protein assemblies involved in human diseases. He is responsible for a number of groundbreaking discoveries in the key structures and molecular interactions involved in the targeted degradation of pathological proteins, paving the way for new approaches to drug discovery in cancer. In recognition of his pioneering work, Prof. Thom\u00e4 received the Otto Naegeli Prize, one of the most prestigious Swiss medical research awards, in 2022. He is also one of only a handful of researchers to have secured three consecutive European Research Council grants (in 2010, 2015 and 2020).<\/p>\n

Research Area<\/strong><\/span><\/p>\n

Protein-protein interactions play a role in all cell fate decisions. The alteration of these interactions and the signaling processes that they regulate are at the heart of virtually every human disease. Reprogramming protein-protein interactomes thus offers enormous opportunities for therapeutic intervention. Recent advances in targeted protein degradation have shown that small molecules can efficiently induce the reprogramming of protein-protein interactions, often by inducing novel contacts. Therapeutically important protein-mediated cell-cell interactions can also be generated through the use of synthetic biology or cellular reprogramming, as used in T cell therapies. Both innovations hold tremendous promise and have in a short time yielded recognizable therapeutic breakthroughs for clinical application. However, to improve such approaches, one needs a deeper understanding of protein-protein interfaces and the capacity to reprogram or generate them. Recent breakthroughs in the computational prediction of protein structures and the analysis of protein-protein interfaces have opened the door to designer therapies based on either molecular glues or designer binding interfaces in recombinant proteins expressed on the cell surface. This will be the approach taken by Prof Nicolas Thom\u00e4, who in collaboration with chemists, AI and medical experts at the EPFL and CHUV will use modeling-driven protein design and novel screening methods to predict and modulate protein-protein interactions.<\/p>\n

The particular specialty of Prof. Thom\u00e4 are small molecules called \u201cmolecular glues\u201d, which are small chemical entities that promote interactions between two proteins.\u00a0 His laboratory has characterized a number of molecular glue compounds that either regulate protein stability by targeting the protein they bind to a ubiquitin ligase, or else mediate other protein-protein interactions, with other outcomes.\u00a0 Using this strategy to engineer receptor-ligand interactions on the surface of T cells and other disease-relevant hematopoietic cells may yield new ways to improve cancer immunotherapy. And if successful, the method may be used to address human diseases beyond cancer.<\/p>\n

The prediction and manipulation of protein-protein interfaces through engineered T cell receptors will be coupled with Prof. Thom\u00e4\u2019s expertise in specifically designed small compounds. This type of synthetic biology requires high-throughput molecular screening combined with cell-based assays which provide the relevant biological context and appropriate therapeutic readouts for disease-relevant models. Prof. Thom\u00e4 aims to combine modeling-based protein engineering and small molecule approaches to optimize protein interactomes, opening the door for more efficacious cancer therapy. He himself contributes experience in cutting-edge technologies such as cryogenic electron microscopy, high throughput genomic screening, and computation-enabled protein design.<\/p>\n

Specific projects will include:<\/p>\n