Projects

ERC Starting Grant SUMOwriteNread (01/2023-12/2027)

The “SUMOwriteNread” project, dedicated to mechanisms of protein SUMOylation and its functional consequences, currently involves PhD students, Lucija Mance and Aanchal Mishra, a postdoc, El hadji Cisse, permanent engineers, Stéphane Goffinont and Franck Coste, and myself as a supervisor. We receive a lot of help from other group members and other scientists from the CBM and beyond.

What is protein SUMOylation? Small ubiquitin-like modifiers (SUMOs), discovered about 25 years ago, are members of the superfamily of ubiquitin-like proteins. We speak of protein SUMOylation when these proteins become covalently attached to intracellular target proteins, modifying their function, location or stability. SUMOylation plays an essential role in many biological functions and has strong links to disease, especially cancer. SUMOylation typically depends on enzymes called E3 ligases. Few SUMO E3 enzymes have been identified and characterised. The ERC-funded SUMOwriteNread project will fill this gap, identifying the structure and mechanism of action of some SUMO E3 ligases, developing approaches to identify and characterise new SUMO E3s, investigate mechanisms by which the specificity of SUMOylation is achieved, and finally to investigate the functional impact of SUMOylation in terms of triggering new protein:protein interactions.

The project is funded by a European Research Council (ERC) Starting Grant (ID 101078837) from the European Union, as part of the Horizon Europe programme. It is active from January 2023 until December 2027. Our budget amounts to € 1 493 515.

HFSP Early Career TFilament (09/2025-08/2028)

Within the framework of the SUMOWriteNread described above, when studying the SUMOylation of proteins from the ZBTB transcription factor family, we accidentally discovered that several proteins from this family have a tendency to form protein filaments. This finding prompted us to ask: Is filament formation a frequent, but overlooked, feature of proteins involved in transcriptional regulation? DNA is inherently an elongated, repetitive molecule, and motifs engaging transcription factors are known to be often repeated in tandem; it would therefore seem logical that proteins that recognise DNA to regulate genes could frequently self-assemble into elongated, repetitive structures. To make the long story short, these ideas have matured into a project, which we constructed together with two collaborators: Max Staller from Berkeley, who studies gene regulation in cells using a combination of high-throughput assays and sophisticated data analysis, and Antoni Wróbel at Oxford, a structural biologist mainly specialised in viral proteins. We are about to launch this collaborative project on 1st September 2025. The project was selected for funding by Human Frontiers Science Program (HFSP) an organisation supporting frontier research. Better known for postdoctoral fellowships, HFSP also finances a few dozen research projects every year, with an emphasis on “intercontinental collaborations”. The total funding amounts to 1.2 million American dollars. In our group, the project will involve a PhD student and a technician, in addition to a partial contribution by several permanent members. The details are to follow.

Here follows a brief, simplified description of the project: The regulation of gene expression is essential for development,stressresponses, and homeostasis. During this process, the information encoded in the genome isturned into functional proteins. Transcription of a deoxyribonucleic acid (DNA) segment creates a ribonucleic acid (RNA) molecule, which acts as a blueprint to make a protein, a functional component of the cell. The transcription of genesinto RNA isregulated by proteins called transcription factors. Transcription factors have two main functions: they bind to specific DNA sequences and either activate or represstranscription. Traditionally, it was believed that transcription factors worked alone or in pairs. However, recent research has unveiled a surprising twist: many transcription factors often join forces, forming larger assemblies of moleculesthat together navigate DNA to identify specific regions. The nature of these assembliesis poorly understood. Our project focuses on one particular category of these assemblies called filaments. Filaments are open-ended, rod-like structures composed of multiple copies of the same protein. Based on our preliminary analysis, we propose that many human transcription factors might have unreported abilitiesto form filaments, which would allow them to simultaneously bind to long DNA sequences. To study how filament formation affectsthe function of transcription factors and how general this mechanism is, we will rely on various approaches. First, we will use experiments, computational analysis, and machine learning to study known examples of filamentation. We will also use cryo-electron microscopy, an imaging technique suited for tiny objects, to study structures of filamentsformed by transcription factorsin the presence or absence of DNA. Finally, we will employ a transformative software called AlphaFold to predict new human transcription factors with a propensity to form filaments. Overall, the project will establish the prevalence and importance of filamentation as a mechanism by which transcription factorsregulate expression of human genes.

Institut National du Cancer PLBIO project on PARP1 and SUMOylation (09/2025-08/2028)

We are also partners on a project funded by the French Institut National du Cancer and dedicated to “the role of SUMOylation signaling in the sensitivity to PARP inhibitors”. The project is led by Sebastien Huet from Rennes and also involves Caroline Goupille and Marie Potier-Cartereau from Tours and Michael Nielsen and Ivo Hendriks from Copenhagen. In our lab, the project currently involves the PhD student Lucija Mance and we hope to recruit a postdoc on this project in early 2026. This project builds on a smaller, one-year grant on PARP1 and SUMOylation funded by Ligue contre le Cancer, of which I was a recipient in 2023.

In addition to these main funded projects, we have several other active small projects related to protein modifications and protein interactions.