Publications de Sandrine Madeleine Suzanne Georgeon

Targeting protein-ligand neosurfaces with a generalizable deep learning tool

Luc Reymond, Sebastian Maerkl, Philippe Schwaller, Sandrine Madeleine Suzanne Georgeon, Anthony Marchand, Bruno Emanuel Ferreira De Sousa Correia, Pablo Gainza Cirauqui, Leo Scheller, Stephen Michael Buckley, Arne Schneuing, Martin Pacesa

Molecular recognition events between proteins drive biological processes in living systems1. However, higher levels of mechanistic regulation have emerged, in which protein-protein interactions are conditioned to small molecules2, 3, 4-5. Despite recent ad ...

NATURE PORTFOLIO2025

An atlas of protein homo-oligomerization across domains of life

Sandrine Madeleine Suzanne Georgeon, Bruno Emanuel Ferreira De Sousa Correia, Casper Alexander Goverde, Martin Pacesa, Yoan Désiré Duhoo

Protein structures are essential to understanding cellular processes in molecular detail. While advances in artificial intelligence revealed the tertiary structure of proteins at scale, their quaternary structure remains mostly unknown. We devise a scalabl ...

2024

Antibody-peptide conjugates deliver covalent inhibitors blocking oncogenic cathepsins

Luc Reymond, Florence Pojer, Albert Santamaria Martinez, Sandrine Madeleine Suzanne Georgeon, Aaron Simone Petruzzella, Bruno Emanuel Ferreira De Sousa Correia, Elisa Oricchio, Natalya Katanayeva, Sarah Wehrle, Kelvin Ka Ching Lau

Cysteine cathepsins are a family of proteases that are relevant therapeutic targets for the treatment of different cancers and other diseases. However, no clinically approved drugs for these proteins exist, as their systemic inhibition can induce deleterio ...

Nature Portfolio2024

Exploring “dark-matter” protein folds using deep learning

Pierre Vandergheynst, Sandrine Madeleine Suzanne Georgeon, Bruno Emanuel Ferreira De Sousa Correia, Zander Harteveld, Andreas Loukas, Stéphane Rosset, Alexandra Krina Van Hall-Beauvais, Casper Alexander Goverde

De novo protein design explores uncharted sequence and structure space to generate novel proteins not sampled by evolution. A main challenge in de novo design involves crafting “designable” structural templates to guide the sequence searches toward adoptin ...

2024

Dual ON/OFF-switch chimeric antigen receptor controlled by two clinically approved drugs

Sandrine Madeleine Suzanne Georgeon, Bruno Emanuel Ferreira De Sousa Correia, Sailan Shui, Leo Scheller

The ability to remotely control the activity of chimeric antigen receptors (CARs) with small molecules can improve the safety and efficacy of gene-modified T cells. Split ON- or OFF-switch CARs involve the dissociation of tumor–antigen binding from T cell ...

National Academy of Sciences2024

Computational design of soluble and functional membrane protein analogues

Sandrine Madeleine Suzanne Georgeon, Bruno Emanuel Ferreira De Sousa Correia, Stéphane Rosset, Casper Alexander Goverde, Martin Pacesa

De novo design of complex protein folds using solely computational means remains a substantial challenge1. Here we use a robust deep learning pipeline to design complex folds and soluble analogues of integral membrane proteins. Unique membrane topologies, ...

2024

Rational Design of Chemically Controlled Antibodies and Protein Therapeutics

Sandrine Madeleine Suzanne Georgeon, Anthony Marchand, Bruno Emanuel Ferreira De Sousa Correia, Pablo Gainza Cirauqui, Li Tang, Sailan Shui, Stéphane Rosset, Lucia Bonati, Leo Scheller

Protein-based therapeutics, such as monoclonal antibodies and cytokines, are important therapies for various pathophysiological conditions such as oncology, autoimmune disorders, and viral infections. However, the wide application of such protein therapeut ...

2023

De novo design of protein interactions with learned surface fingerprints

Henning Paul-Julius Stahlberg, Didier Trono, Priscilla Turelli, Charlène Mireille Raymonde Raclot, Sandrine Madeleine Suzanne Georgeon, Beat Fierz, Aaron Simone Petruzzella, Anthony Marchand, Bruno Emanuel Ferreira De Sousa Correia, Elisa Oricchio, Zander Harteveld, Pablo Gainza Cirauqui, Freyr Sverrisson, Andreas Scheck, Sarah Wehrle, Stéphane Rosset, Alexandra Krina Van Hall-Beauvais, Alexandra Teslenko, Jane Marsden, Michael Bronstein, Casper Alexander Goverde, Stephen Michael Buckley, Dongchun Ni, Martin Pacesa

Physical interactions between proteins are essential for most biological processes governing life. However, the molecular determinants of such interactions have been challenging to understand, even as genomic, proteomic and structural data increase. This k ...

2023

De Novo Design of Site-specific Protein Binders Using Surface Fingerprints

Sandrine Madeleine Suzanne Georgeon, Aaron Simone Petruzzella, Elisa Oricchio, Zander Harteveld, Pablo Gainza Cirauqui, Freyr Sverrisson, Andreas Scheck, Sarah Wehrle, Stéphane Rosset, Alexandra Krina Van Hall-Beauvais

WILEY2021

Bottom-up de novo design of functional proteins with complex structural features

Sandrine Madeleine Suzanne Georgeon, Luciano Andres Abriata, Bruno Emanuel Ferreira De Sousa Correia, Jaume Bonet Martinez, Fabian Sesterhenn, Che Yang, Stéphane Rosset, Eva Anna van Aalen, Leo Scheller

De novo protein design has enabled the creation of new protein structures. However, the design of functional proteins has proved challenging, in part due to the difficulty of transplanting structurally complex functional sites to available protein structur ...

2021

De novo protein design enables the precise induction of RSV-neutralizing antibodies

Patricia Corthésy Henrioud, Sandrine Madeleine Suzanne Georgeon, Luciano Andres Abriata, Bruno Emanuel Ferreira De Sousa Correia, Elisa Oricchio, Jaume Bonet Martinez, Fabian Sesterhenn, Che Yang, Sabrina Susan Vollers, Mélanie Evelyne Villard, Elie Charles Eugène Dheilly, Stéphane Rosset, Yujia Wang

De novo protein design has been successful in expanding the natural protein repertoire. However, most de novo proteins lack biological function, presenting a major methodological challenge. In vaccinology, the induction of precise antibody responses remain ...

American Association for the Advancement of Science2020

Btk SH2-kinase interface is critical for allosteric kinase activation and its targeting inhibits B-cell neoplasms

Florence Pojer, Matteo Dal Peraro, Oliver Hantschel, Sandrine Madeleine Suzanne Georgeon, Allan Joaquim Lamontanara, Tim Kükenshöner, Maria Josefina Marcaida Lopez, Daniel Pereira Duarte, Grégory La Sala

Bruton's tyrosine kinase (Btk) is critical for B-cell maturation and activation. Btk loss-of-function mutations cause human X-linked agammaglobulinemia (XLA). In contrast, Btk signaling sustains growth of several B-cell neoplasms which may be treated with ...

Nature Publishing Group2020

Computational design of anti-CRISPR proteins with improved inhibition potency

Wei Sun, Sandrine Madeleine Suzanne Georgeon, Bruno Emanuel Ferreira De Sousa Correia, Zander Harteveld, Andreas Scheck, Stéphane Rosset, Julius Valten Upmeier Zu Belzen, Yujia Wang

Anti-CRISPR (Acr) proteins are powerful tools to control CRISPR-Cas technologies. However, the available Acr repertoire is limited to naturally occurring variants. Here, we applied structure-based design on AcrIIC1, a broad-spectrum CRISPR-Cas9 inhibitor, ...

NATURE PUBLISHING GROUP2020

Rapid Screen for Tyrosine Kinase Inhibitor Resistance Mutations and Substrate Specificity

Oliver Hantschel, Sandrine Madeleine Suzanne Georgeon, Sina Maren Reckel

We present a rapid and high-throughput yeast and flow cytometry based method for predicting kinase inhibitor resistance mutations and determining kinase peptide substrate specificity. Despite the widespread success of targeted kinase inhibitors as cancer t ...

AMER CHEMICAL SOC2019

Kinase-templated abiotic reaction

Oliver Hantschel, Sandrine Madeleine Suzanne Georgeon

Protein kinases are quintessential regulators of cellular function. Numerous pathologies are intimately linked to the dysregulated activity of a particular protein kinase. Herein we report a technology based on a proximity-induced chemical transformation t ...

2017

Differential signaling networks of Bcr-Abl p210 and p190 kinases in leukemia cells defined by functional proteomics

Romain Hamelin, Oliver Hantschel, Sandrine Madeleine Suzanne Georgeon, Sina Maren Reckel

The two major isoforms of the oncogenic Bcr-Abl tyrosine kinase, p210 and p190, are expressed upon the Philadelphia chromosome translocation. p210 is the hallmark of chronic myelogenous leukemia, whereas p190 occurs in the majority of B-cell acute lymphobl ...

Nature Publishing Group2017

Structural and functional dissection of the DH and PH domains of oncogenic Bcr-Abl tyrosine kinase

Florence Pojer, Oliver Hantschel, Sandrine Madeleine Suzanne Georgeon, Delphine Maude Tardivon, Sina Maren Reckel, Barbara Gerig, Tim Kükenshöner, Sara Raquel Pereira Pinho, Charlotte Julie Caroline Gehin

The two isoforms of the Bcr-Abl tyrosine kinase, p210 and p190, are associated with different leukemias and have a dramatically different signaling network, despite similar kinase activity. To provide a molecular rationale for these observations, we study ...

Springer Nature2017

Single-molecule kinetic analysis of HP1-chromatin binding reveals a dynamic network of histone modification and DNA interactions

Vassily Hatzimanikatis, Louise Catherine Bryan, Georg Fantner, Pascal Damian Odermatt, Oliver Hantschel, Sandrine Madeleine Suzanne Georgeon, Beat Fierz, Sinan Kilic, Carolin Christine Lechner, Andreas Linus Bachmann, Daniel Robert Weilandt

Chromatin recruitment of effector proteins involved in gene regulation depends on multivalent interaction with histone post-translational modifications (PTMs) and structural features of the chromatin fiber. Due to the complex interactions involved, it is c ...

Oxford University Press (OUP)2017

The SH2 domain of Abl kinases regulates kinase autophosphorylation by controlling activation loop accessibility

Oliver Hantschel, Sandrine Madeleine Suzanne Georgeon, Allan Joaquim Lamontanara

The activity of protein kinases is regulated by multiple molecular mechanisms, and their disruption is a common driver of oncogenesis. A central and almost universal control element of protein kinase activity is the activation loop that utilizes both confo ...

Nature Research2014

Specificity and mechanism-of-action of the JAK2 tyrosine kinase inhibitors ruxolitinib and SAR302503 (TG101348)

Roland Moser, Oliver Hantschel, Sandrine Madeleine Suzanne Georgeon

Nature Publishing Group2014