Publications related to Threonine eliminylation by bacterial phosphothreonine lyases rapidly causes cross-linking of mitogen-activated protein kinase (MAPK) in live cells

AMP-activated Protein Kinase (AMPK): New molecular insights and novel downstream targets

AMP-activated Protein Kinase (AMPK) is a central regulator of energy homeostasis and a promising drug target for metabolic disorders. It exists as complexes of three subunits, a catalytic alpha, and two regulatory beta and gamma subunits. The regulation of ...

EPFL2022

Real-time monitoring of single-cell secretion with a high-throughput nanoplasmonic microarray

Hatice Altug, Xiaokang Li, Yen-Cheng Liu, Eduardo Romero Arvelo, Saeid Ansaryan

Proteins secreted by cells play significant roles in mediating many physiological, developmental, and pathological processes due to their functions in intra/intercellular communication and signaling. Conventional end-point methods are insufficient for unde ...

Elsevier2022

Polarly Localized EccE(1) Is Required for ESX-1 Function and Stabilization of ESX-1 Membrane Proteins in Mycobacterium tuberculosis

Stewart Cole, Claudia Sala, Ming Zhang, Jérémie Piton, Paloma Julia Soler Arnedo

Mycobacterium tuberculosis is a slow-growing intracellular bacterium with the ability to induce host cell death and persist indefinitely in the human body. This pathogen uses the specialized ESX-1 secretion system to secrete virulence factors and potent im ...

American Society for Microbiology2020

Label-free plasmonic biosensors for real-time live cell analysis

Xiaokang Li

For decades, the understanding of life has been focused on its most fundamental building blocks: molecules. Deciphering the dynamic activities of protein molecules in human cells is of vital significance for fundamental and clinical studies. The minuscule ...

EPFL2019

Cytosolic delivery and characterization of monobodies interfering with SH2 domain-phosphotyrosine interactions

Nadine Eliane Schmit

Targeted cancer therapy is a very promising concept; however, small molecule inhibitors only exist for a limited number of oncoproteins and resistance development limits their clinical use. Different engineered non-antibody scaffolds are being explored to ...

EPFL2018

Plasmonic nanohole array biosensor for label-free and real-time analysis of live cell secretion

Hatice Altug, Alexander Belushkin, Filiz Yesilköy, Xiaokang Li, Maria Soler Aznar, Cenk Ibrahim Özdemir

Cell secretion dynamics plays a central role in physiological and disease processes. Due to its various temporal profiles, it is essential to implement a precise detection scheme for continuous monitoring of secretion in real time. The current fluorescent ...

Royal Society of Chemistry2017

Structural and functional characterization of the mycobacterial ESX-1 secretion system

Ye Lou

Human tuberculosis (TB) is a frequently fatal lung disease mostly caused by Mycobacterium tuberculosis (M. tb), a slow-growing intracellular pathogen. M. tb utilizes the ESX-1 secretion system, classified as type VII, to export the virulence factors needed ...

EPFL2016

The PhoP-Dependent ncRNA Mcr7 Modulates the TAT Secretion System in Mycobacterium tuberculosis

Stewart Cole, Claudia Sala, Swapna Uplekar, Jacques Rougemont, Andrej Benjak

The PhoPR two-component system is essential for virulence in Mycobacterium tuberculosis where it controls expression of approximately 2% of the genes, including those for the ESX-1 secretion apparatus, a major virulence determinant. Mutations in phoP lead ...

Public Library of Science2014

Anticytolytic Screen Identifies Inhibitors of Mycobacterial Virulence Protein Secretion

Stewart Cole, Claudia Sala, Jeffrey Chen, Ruben Hartkoorn, Ming Zhang, Edina Rita Székely, Jan Lars Rybniker, Anthony Vocat, Andrej Benjak

Mycobacterium tuberculosis (Mtb) requires protein secretion systems like ESX-1 for intracellular survival and virulence. The major virulence determinant and ESX-1 substrate, EsxA, arrests phagosome maturation and lyses cell membranes, resulting in tissue d ...

Cell Press2014

In situ structural analysis of the Yersinia enterocolitica injectisome

Henning Paul-Julius Stahlberg, Matteo Thomas Degiacomi, Matteo Dal Peraro, Marco Stenta

Injectisomes are multi-protein transmembrane machines allowing pathogenic bacteria to inject effector proteins into eukaryotic host cells, a process called type III secretion. Here we present the first three-dimensional structure of Yersinia enterocolitica ...

Elife Sciences Publications Ltd2013

Molecular Modeling of Bacterial Nanomachineries

Matteo Thomas Degiacomi

Proteins have the ability to assemble in multimeric states to perform their specific biological function. Unfortunately, characterizing experimentally these structures at atomistic resolution is usually difficult. For this reason, in silico methodologies a ...

EPFL2012

Folding and Structure of the Pore Forming Toxin Aerolysin

Mircea Ioan Iacovache

The first obstacle encountered by a bacterial pathogen once inside the host is the plasma membrane surrounding the target cells. Throughout evolution bacteria has acquired and maintained genes that upon stimulation express proteins capable of damaging the ...

EPFL2011

Two Nucleus-Localized CDK-Like Kinases With Crucial Roles for Malaria Parasite Erythrocytic Replication Are Involved in Phosphorylation of Splicing Factor

The kinome of the human malaria parasite Plasmodium falciparum comprises representatives of most eukaryotic protein kinase groups, including kinases which regulate proliferation and differentiation processes. Despite extensive research on most plasmodial e ...

Wiley-Blackwell2011

Hybrid Polymer Therapeutics Incorporating Bioresponsive, Coiled Coil Peptide Linkers

Nanopharmaceuticals or nanomedicines are defined as nanometer sized (1 to 1000 nm) complex systems, consisting of at least two components, one of which being the biologically active moiety such as a drug, peptide, protein or nucleotide. Several nano-sized ...

EPFL2010

Metabolic Labeling and Protein Linearization Technology Allow the Study of Proteins Secreted by Cultured Cells in Serum-Containing Media

Supernatants from cell cultures (also called conditioned media, CMs) are commonly analyzed to study the pool of secreted proteins (secretome). To reduce the exogenous protein background, serum-free media are often used to obtain CMs. Serum deprivation, how ...

2009

Control of M. tuberculosis ESAT-6 secretion and specific T cell recognition by PhoP

Stewart Cole

Analysis of mycobacterial strains that have lost their ability to cause disease is a powerful approach to identify yet unknown virulence determinants and pathways involved in tuberculosis pathogenesis. Two of the most widely used attenuated strains in the ...

2008

Novel applications of poly(ethylene glycol)-bl-poly(propylene sulfide) block copolymers

Conlin O'Neil

Block copolymers are comprised of repeating chemical groups (blocks) which commonly contain at least one hydrophilic block coupled to at least one hydrophobic block, forming an amphipathic macromolecule. This molecular arrangement drives the self assembly ...

EPFL2008

A protein linkage map of the ESAT-6 secretion system 1 (ESX-1) of Mycobacterium tuberculosis

Stewart Cole

Tuberculosis is a chronic infectious disease caused by bacteria of the Mycobacterium tuberculosis complex. One of the major contributors to virulence and intercellular spread of M. tuberculosis is the ESAT-6 secretion system 1 (ESX-1) that has been lost by ...

2007

A century-old debate on protein aggregation and neurodegeneration enters the clinic

Hilal Lashuel

The correlation between neurodegenerative disease and protein aggregation in the brain has long been recognized, but a causal relationship has not been unequivocally established, in part because a discrete pathogenic aggregate has not been identified. The ...

2006