Publications associées à Évolution dirigée

Development of cysteine cathepsin inhibitors combined with cell type-specific delivery for the treatment of B-cell lymphoma and solid tumors

Cysteine cathepsins proteases are enzymes that play essential physiological roles, but their activity is also associated to different aspects of cancer progression and to the development of other diseases. Therefore, cysteine cathepsins are relevant and pr ...

EPFL2024

HaloTag-Based Tools for Live-Cell Imaging and Elucidation of Organellar Redox Biology

Sarah Emmert

Redox homeostasis is a key factor in maintaining cellular function and health. The main determinant of the intracellular redox potential is ubiquitous glutathione (GSH) together with its oxidized dimer (GSSG). Importantly, both redox equilibrium and GSH ho ...

EPFL2024

Site-selective template-directed synthesis of antibody Fc conjugates with concomitant ligand release

Natalia Gasilova, Jean-Manuel Segura, David Viertl

Template-directed methods are emerging as some of the most effective means to conjugate payloads at selective sites of monoclonal antibodies (mAbs). We have previously reported a method based on an engineered Fc-III reactive peptide to conjugate a radionuc ...

Royal Soc Chemistry2023

Design of an artificial phage-display library based on a new scaffold improved for average stability of the randomized proteins

Ghérici Hassaïne

Scaffold-based protein libraries are designed to be both diverse and rich in functional/folded proteins. However, introducing an extended diversity while preserving stability of the initial scaffold remains a challenge. Here we developed an original approa ...

Nature Portfolio2023

Substrates and Cyclic Peptide Inhibitors of the Oligonucleotide-Activated Sirtuin 7

Alexander Lund Nielsen

The sirtuins are NAD+-dependent lysine deacylases, comprising seven isoforms (SIRT1-7) in humans, which are involved in the regulation of a plethora of biological processes, including gene expression and metabolism. The sirtuins share a common hydrolytic m ...

Wiley-VCH Verlag GmbH2023

Extracting phylogenetic dimensions of coevolution reveals hidden functional signals

Anne-Florence Raphaëlle Bitbol

Despite the structural and functional information contained in the statistical coupling between pairs of residues in a protein, coevolution associated with function is often obscured by artifactual signals such as genetic drift, which shapes a protein's ph ...

Nature Portfolio2022

Regulation of sedimentation rate shapes the evolution of multicellularity in a close unicellular relative of animals

Omaya Pierre Dudin

Significant increases in sedimentation rate accompany the evolution of multicellularity. These increases should lead to rapid changes in ecological distribution, thereby affecting the costs and benefits of multicellularity and its likelihood to evolve. How ...

PUBLIC LIBRARY SCIENCE2022

How Vibrio cholerae adapts to the environment: from cell shape transitions to antagonistic behavior

Leonardo Filipe Lemos Rocha

The bacterium Vibrio cholerae is the causative agent of the diarrheal disease cholera, which affects millions of people every year. Apart from being a human pathogen, V. cholerae is also a common member of aquatic habitats. Whilst the mechanism that allow ...

EPFL2022

Directed evolution of DNA-wrapped single-walled carbon nanotube complexes for optical sensing

Benjamin Paul Johanès Gabriel Lambert

Single-walled carbon nanotubes (SWCNTs) have garnered significant interest for their applications in optical biosensing. SWCNTs exhibit a sensitive and photostable fluorescence in the near-infrared (NIR) range, allowing for the continuous monitoring of tar ...

EPFL2021

Alternative dimerization is required for activity and inhibition of the HEPN ribonuclease RnlA

Gabriela Garcia Rodriguez

The rnlAB toxin-antitoxin operon from Escherichia co/ifunctions as an anti-phage defense system. RnlA was identified as a member of the HEPN (Higher Eukaryotes and Prokaryotes Nucleotide-binding domain) superfamily of ribonucleases. The activity of the tox ...

OXFORD UNIV PRESS2021

Towards an Evolutionary Theory of Stress Responses

Maria del Carmen Sandi Perez

All organisms have a stress response system to cope with environmental threats, yet its precise form varies hugely within and across individuals, populations, and species. While the physiological mechanisms are increasingly understood, how stress responses ...

2021

Constraint-based metabolic control analysis for rational strain engineering

Vassily Hatzimanikatis, Ljubisa Miskovic, Meriç Ataman, Tuure Eelis Hameri, Sofia Tsouka

The advancements in genome editing techniques over the past years have rekindled interest in rational metabolic engineering strategies. While Metabolic Control Analysis (MCA) is a well-established method for quantifying the effects of metabolic engineering ...

2021

On the exploration of novel methodological approaches for immunogen design: case studies in influenza and hepatitis C

Andreas Scheck

Proteins are fundamental components in biological systems and crucial for a variety of biological functions. Over the last decades, significant progress in structural biology has facilitated the study of proteins and their interactions with molecular partn ...

EPFL2021

Protein Structural Information and Evolutionary Landscape by In Vitro Evolution

Paolo De Los Rios

Protein structure is tightly intertwined with function according to the laws of evolution. Understanding how structure determines function has been the aim of structural biology for decades. Here, we have wondered instead whether it is possible to exploit ...

OXFORD UNIV PRESS2020

Direct coupling analysis of epistasis in allosteric materials

Matthieu Wyart, Riccardo Ravasio, Carolina Brito Carvalho dos Santos, Barbara Bravi

In allosteric proteins, the binding of a ligand modifies function at a distant active site. Such allosteric pathways can be used as target for drug design, generating considerable interest in inferring them from sequence alignment data. Currently, differen ...

2020

Single-molecule sensing of peptides and nucleic acids by engineered aerolysin nanopores

Aleksandra Radenovic, Matteo Dal Peraro, Chan Cao, Nuria Cirauqui Diaz, Alice Duperrex, Elena Buglakova

Nanopore sensing is a powerful single-molecule approach for the detection of biomolecules. Recent studies have demonstrated that aerolysin is a promising candidate to improve the accuracy of DNA sequencing and to develop novel single-molecule proteomic str ...

Nature Research2019

Probing the interaction of nanoparticles with small molecules in real time via quartz crystal microbalance monitoring

Stefan Guldin, Nikolaos Nianias, Ye Yang, Runzhang Qi

Despite extensive advances in the field of molecular recognition, the real-time monitoring of small molecule binding to nanoparticles (NP) remains a challenge. To this end, we report on a versatile approach, based on quartz crystal microbalance with dissip ...

2019

Active Site-Induced Evolutionary Constraints Follow Fold Polarity Principles in Soluble Globular Enzymes

Matteo Dal Peraro, Luciano Andres Abriata, Alexander Mayorov

A recent analysis of evolutionary rates in >500 globular soluble enzymes revealed pervasive conservation gradients toward catalytic residues. By looking at amino acid preference profiles rather than evolutionary rates in the same data set, we quantified th ...

OXFORD UNIV PRESS2019

Sexual conflict drives male manipulation of female postmating responses in Drosophila melanogaster

Laurent Keller, Brian Dennis Hollis

In many animals, females respond to mating with changes in physiology and behavior that are triggered by molecules transferred by males during mating. In Drosophila melanogaster, proteins in the seminal fluid are responsible for important female postmating ...

National Academy of Sciences2019

Rapid Screen for Tyrosine Kinase Inhibitor Resistance Mutations and Substrate Specificity

Sandrine Madeleine Suzanne Georgeon, Oliver Hantschel, 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