Publications associées à Deciphering the molecular basis of mycobacteria and lipoglycan recognition by the C-type lectin Dectin-2

Single-cell analysis of the interactions between Mycobacterium tuberculosis and macrophages

Mycobacterium Tuberculosis is a highly effective pathogen infecting nearly a third of the world's population. An M. tuberculosis infection starts when droplets containing bacteria enter an individual's lungs. The first host cells to contact the bacteria ar ...

EPFL2024

From Sequence to Dynamics to Function: Computational Design of Allostery and Ligand Selectivity in G-Protein Coupled Receptors

Mahdi Hijazi

The phenomenon of allostery, a general property in proteins that has been heralded as "the second secret of life" remains elusive to our understanding and even more challenging to incorporate into protein design. One example of allosteric proteins with gre ...

EPFL2024

Bacterial diversity dominates variable macrophage responses of tuberculosis patients in Tanzania

Jacques Fellay, Zhi Ming Xu

The Mycobacterium tuberculosis complex (MTBC) comprises nine human-adapted lineages that differ in their geographical distribution. Local adaptation of specific MTBC genotypes to the respective human host population has been invoked in this context. We aim ...

Nature Portfolio2024

Human alveolar lining fl uid from the elderly promotes Mycobacterium tuberculosis intracellular growth and translocation into the cytosol of alveolar epithelial cells

Vivek Vijay Thacker, Richa Mishra

The elderly population is highly susceptible to developing respiratory diseases, including tuberculosis, a devastating disease caused by the airborne pathogen Mycobacterium tuberculosis ( M.tb ) that kills one person every 18 seconds. Once M.tb reaches the ...

Elsevier Science Inc2024

Machine learning-aided generative molecular design

Philippe Schwaller, Jeff Guo

Machine learning has provided a means to accelerate early-stage drug discovery by combining molecule generation and filtering steps in a single architecture that leverages the experience and design preferences of medicinal chemists. However, designing mach ...

Nature Portfolio2024

Computational drug development for membrane protein targets

Henning Paul-Julius Stahlberg, Pierre Vogel, Shuguang Yuan, Dongchun Ni, Babatunde Edukpe Ekundayo

The application of computational biology in drug development for membrane protein targets has experienced a boost from recent developments in deep learning-driven structure prediction, increased speed and resolution of structure elucidation, machine learni ...

2024

Unlocking Hidden Potential: Exploring the Complexities of Signaling in Immune Cell Activation to Optimize CAR Therapy

Mathieu Girardin

Chimeric antigen receptors (CARs) are synthetic, transmembrane proteins that trigger immune cell signaling following their engagement. They have been first utilized in T cells and later in natural killer (NK) cells to redirect their cytotoxicity toward a s ...

EPFL2023

Investigating the composition and recruitment of the mycobacterial ImuA'-ImuB-DnaE2 mutasome

John McKinney, Neeraj Dhar, Zela Alexandria-Mae Martin

A DNA damage-inducible mutagenic gene cassette has been implicated in the emergence of drug resistance in Mycobacterium tuberculosis during anti-tuberculosis (TB) chemotherapy. However, the molecular composition and operation of the encoded 'mycobacterial ...

Elife Sciences Publ Ltd2023

Back-to-Africa introductions of Mycobacterium tuberculosis as the main cause of tuberculosis in Dar es Salaam, Tanzania

Jacques Fellay, Zhi Ming Xu

In settings with high tuberculosis (TB) endemicity, distinct genotypes of the Mycobacterium tuberculosis complex (MTBC) often differ in prevalence. However, the factors leading to these differences remain poorly understood. Here we studied the MTBC populat ...

PUBLIC LIBRARY SCIENCE2023

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

Exploring the interplay of molecular pattern and valency for selective interactions at the bio-interface

Kaltrina Paloja

Cell-cell communication is fundamental for immune balance. Multivalent interactions of surface receptors at immune interfaces drive specific communication, with stimulatory and inhibitory signals guiding the immune outcome. Notably, the valency, affinity, ...

EPFL2023

Development of a novel Chimeric Antigen Receptor (CAR) for its use in Natural Killer (NK) cells for cancer treatment and beyond

Angela Madurga Alonso

The use of CAR technologies has revolutionized cancer treatment. Their unprecedented efficacy against B cell malignancies has opened the doors for a lot of excitement and research in the field. These synthetic receptors are composed of an antigen recogniti ...

EPFL2023

A Geometric Transformer for Structural Biology: Development and Applications of the Protein Structure Transformer

Lucien Fabrice Krapp

Proteins, the central building blocks of life, play pivotal roles in nearly every biological function. To do so, these macromolecular structures interact with their surrounding environment in complex ways, leading to diverse functional behaviors. The predi ...

EPFL2023

Two antagonistic response regulators control Pseudomonas aeruginosa polarization during mechanotaxis

Lorenzo Anton-Louis Talà, Alexandre Louis André Persat, Xavier Jean-Yves Pierrat, Marco Julian Kühn, Joanne Netter Engel

The opportunistic pathogen Pseudomonas aeruginosa adapts to solid surfaces to enhance virulence and infect its host. Type IV pili (T4P), long and thin filaments that power surface-specific twitching motility, allow single cells to sense surfaces and contro ...

WILEY2023

How are cells instructed to form somite boundaries by the zebrafish segmentation clock?

Olivier François Venzin

In vertebrate embryos, the elongating body axis is patterned via the sequential and rhyth-mic production of segments from a posterior unsegmented tissue called the presomitic mesoderm (PSM). This process is controlled by a population of cellular oscillator ...

EPFL2023

Regulation and function of a hemicleaved Activin-A processing intermediate in melanoma

Manon Bulliard

Activin-A is a Transforming Growth Factor-B (TGFB)-related cytokine that regulates various biological processes including cell proliferation and differentiation through autocrine, paracrine or endocrine signaling. Activin-A expression is upregulated in mul ...

EPFL2023

Extensive programmed centriole elimination unveiled in C. elegans embryos

Pierre Gönczy, Nils Kalbfuss

Centrioles are critical for fundamental cellular processes, including signaling, motility, and division. The extent to which centrioles are present after cell cycle exit in a developing organism is not known. The stereotypical lineage of Caenorhabditis ele ...

2023

Bioaccumulation and molecular effects of carbamazepine and methylmercury co-exposure in males of Dreissena polymorpha

Dominique Grandjean, Florian Frédéric Vincent Breider, Claudia Cosio, Nguyên Thiên Kim Lê

Dreissena polymorpha is a bivalve promising for biomonitoring in freshwater ecosystems thanks to its abundance and high filtration activity allowing rapid uptake of toxicants and identification of their negative effects. Nonetheless, we still lack knowledg ...

2023

Preexisting Heterogeneity of Inducible Nitric Oxide Synthase Expression Drives Differential Growth of Mycobacterium tuberculosis in Macrophages

John McKinney, Ophélie Rutschmann, Chiara Toniolo

Mycobacterium tuberculosis infection is initiated by the inhalation and implantation of bacteria in the lung alveoli, where they are phagocytosed by macrophages. Even a single bacterium may be sufficient to initiate infection. Thereafter, the clinical outc ...

AMER SOC MICROBIOLOGY2022

Premature Vertebral Mineralization in hmx1-Mutant Zebrafish

H6 family homeobox 1 (HMX1) regulates multiple aspects of craniofacial development, and mutations in HMX1 are linked to an ocular defect termed oculoauricular syndrome of Schorderet-Munier-Franceschetti (OAS) (MIM #612109). Recently, additional altered oro ...

2022