Publications related to Effects of codon distributions and tRNA competition on protein translation

Towards improving full-length ribosome density prediction by bridging sequence and graph-based representations

Felix Naef, Pierre Vandergheynst, Cédric Gobet, Mohan Vamsi Nallapareddy, Francesco Craighero

Translation elongation plays an important role in regulating protein concentrations in the cell, and dysregulation of this process has been linked to several human diseases. In this study, we use data from ribo-seq experiments to model ribosome densities, ...

PMLR2024

Engineering novel protein interactions with therapeutic potential using deep learning-guided surface design

Anthony Marchand

Proteins are foundational biomolecules of life playing a crucial role in a myriad of biological processes. Their function often requires interplay with other biomolecules, including proteins themselves. Protein-protein interactions (PPIs) are essential for ...

EPFL2024

De novo designed proteins: a study in engineering novel folds and functions

Alexandra Krina Van Hall-Beauvais

Proteins control nearly every facet of life on a molecular level. Proteins are formed from linear strings of amino acids, which fold into three-dimensional structures that can enact functions. Evolution has created highly efficient proteins in diverse fold ...

EPFL2023

Development of multiplexed single-molecule imaging techniques to study chromatin invasion dynamics of chromatin effector proteins

Kristina Makasheva

DNA-binding proteins physically interact with the DNA and directly affect genomic functions. The eukaryotic genome is compacted into chromatin, limiting the DNA access to nuclear factors. In this Ph.D. thesis, I explored the dynamic mechanisms, that allow ...

EPFL2023

Generative power of a protein language model trained on multiple sequence alignments

Umberto Lupo, Anne-Florence Raphaëlle Bitbol, Damiano Sgarbossa

Computational models starting from large ensembles of evolutionarily related protein sequences capture a representation of protein families and learn constraints associated to protein structure and function. They thus open the possibility for generating no ...

eLIFE SCIENCES PUBL LTD2023

Ribo-DT: An automated pipeline for inferring codon dwell times from ribosome profiling data

Felix Naef, Cédric Gobet

Protein synthesis is an energy consuming process characterised as a pivotal and highly regulated step in gene expression. The net protein output is dictated by a combination of translation initiation, elongation and termination rates that have remained dif ...

ACADEMIC PRESS INC ELSEVIER SCIENCE2022

Biochemistry of Aminoacyl tRNA Synthetase and tRNAs and Their Engineering for Cell-Free and Synthetic Cell Applications

Sebastian Maerkl, Ragunathan Bava Ganesh

Cell-free biology is increasingly utilized for engineering biological systems, incorporating novel functionality, and circumventing many of the complications associated with cells. The central dogma describes the information flow in biology consisting of t ...

FRONTIERS MEDIA SA2022

Towards automating de novo protein design for novel functionalities: controlling protein folds and protein-protein interactions

Zander Harteveld

The sheer size of the protein sequence space is massive: a protein of 100 residues can have 20^100 possible sequence combinations; and knowing that this exceeds the number of atoms in the universe, the chance of randomly discovering a stable new sequence w ...

EPFL2022

Protein Engineering for Personalized therapy and diagnosis

Lixia Wei

Protein Engineering, especially protein post-translational modification (PTM), ex-tends proteomes in a more complex way than one can expect from analysis of their encod-ing genomes. It can activate or deactivate certain catalytic functions, add new desired ...

EPFL2022

A Rosetta-based protein design protocol converging to natural sequences

Bruno Emanuel Ferreira De Sousa Correia, Zander Harteveld, Giulia Sormani, Stéphane Rosset

Computational protein design has emerged as a powerful tool capable of identifying sequences compatible with pre-defined protein structures. The sequence design protocols, implemented in the Rosetta suite, have become widely used in the protein engineering ...

AMER INST PHYSICS2021

Circadian dynamics of RNA localisation in the mammalian liver

Clémence Yumie Syloun Hurni

Gene expression in eukaryotes is a complex multi-step process. It starts in the nucleus with transcription, the synthesis of a mRNA copy from a DNA template. While in the nucleus, the RNA transcript is subject to multiple co- and post-transcriptional modif ...

EPFL2021

New and improved methods for integrated models of metabolism and gene expression

Pierre Guy Rémy Salvy

The beginning of the 21st century was marked by the advent of disruptive technologies, which ushered an era of groundbreaking advances in fundamental sciences, carried by the great pace at which computational capabilities spread and evolved. But the new ce ...

EPFL2021

m6A methylation potentiates cytosolic dsDNA recognition in a sequence-specific manner

Andrea Ablasser, Muhammet Fatih Gülen

Nucleic acid sensing through pattern recognition receptors is critical for immune recognition of microbial infections. Microbial DNA is frequently methylated at the N-6 position of adenines (m6A), a modification that is rare in mammalian host DNA. We show ...

ROYAL SOC2021

Robust landscapes of ribosome dwell times and aminoacyl-tRNAs in response to nutrient stress in liver

Felix Naef, Cédric Gobet, Frédéric Bruno Martin Gachon, Benjamin Dieter Weger, Nagammal Neelagandan

Translation depends on messenger RNA (mRNA)-specific initiation, elongation, and termination rates. While translation elongation is well studied in bacteria and yeast, less is known in higher eukaryotes. Here we combined ribosome and transfer RNA (tRNA) pr ...

National Academy of Sciences2020

Statistical physics of interacting proteins: Impact of dataset size and quality assessed in synthetic sequences

Anne-Florence Raphaëlle Bitbol, Pierre Mergny

Identifying protein-protein interactions is crucial for a systems-level understanding of the cell. Recently, algorithms based on inverse statistical physics, e.g., direct coupling analysis (DCA), have allowed to use evolutionarily related sequences to addr ...

2020

Neighborhood watch: tools for defining locale-dependent subproteomes and their contextual signaling activities

Yimon Aye, Yi Zhao

Transient associations between numerous organelles-e.g., the endoplasmic reticulum and the mitochondria-forge highly-coordinated, particular environments essential for cross-compartment information flow. Our perspective summarizes chemical-biology tools th ...

ROYAL SOC CHEMISTRY2020

Single-molecule dynamics and genome-wide transcriptomics reveal that NF-kB (p65)-DNA binding times can be decoupled from transcriptional activation

Suliana Manley, Aleksandr Benke, Beat Fierz, Andrea Callegari, David Michael Suter, Christian Sieben

Transcription factors (TFs) regulate gene expression in both prokaryotes and eukaryotes by recognizing and binding to specific DNA promoter sequences. In higher eukaryotes, it remains unclear how the duration of TF binding to DNA relates to downstream tran ...

2019

Allosteric Protein Switches based on Antibody Mimetics

Helen Rebecca Ostlund Farrants

Synthetic protein switches are proteins that can be controlled by an external input, and are useful tools to probe protein function. Antibody fragments and antibody mimetics can be selected to bind, activate, or inhibit several diverse protein targets. Nev ...

EPFL2019

Exploring on Protein-DNA interactions

Alexandra Styliani Kalantzi

A variety of DNA-binding proteins organizes the chromosomal DNA and regulates gene transcription, and DNA replication and recombination. In particular, for gene regulation there is a category of DNA-binding proteins, the transcription factors, which can de ...

EPFL2019

Circadian clock- and feeding-dependent regulation of translation initiation and elongation in the liver

Cédric Gobet

Circadian rhythms allow organisms to anticipate and adapt to periodic environmental changes related to the day-night cycle. These rhythms originate from a genetic network ticking in almost every cell of our body and the coordination between different organ ...

EPFL2018