Publications related to Second messenger system

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

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

Engineering hydrogel microenvironments for epithelial organoid culture

Antonius Chrisnandy

Organoids, miniature tissues generated from self-organizing stem cells within three-dimensional (3D) extracellular matrices (ECM), have opened up exciting possibilities for in vitro studies of complex physiological processes. A key factor in the success of ...

EPFL2024

Quantifying single-cell diacylglycerol signaling kinetics after uncaging

Milena Maria Schuhmacher, Pavel Barahtjan

Studying the role of molecularly distinct lipid species in cell signaling remains challenging due to a scarcity of methods for performing quantitative lipid biochemistry in living cells. We have recently used lipid uncaging to quantify lipid -pro-tein affi ...

Cell Press2023

Rules and mechanisms governing G protein coupling selectivity of GPCRs

Bruno Emanuel Ferreira De Sousa Correia, Pablo Gainza Cirauqui

G protein-coupled receptors (GPCRs) convert extracellular stimuli into intracellular signaling by coupling to heterotrimeric G proteins of four classes: Gi/o, Gq, Gs, and G12/13. However, our understanding of the G protein selectivity of GPCRs is incomplet ...

Cell Press2023

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

Development of methods for the synthesis of large combinatorial libraries of macrocyclic compounds

Mischa Schüttel

Macrocycles have raised much interest in the pharmaceutical industry due to their ability to bind challenging targets while often still being able to cross membranes to reach intracellular proteins. However, the development of macrocyclic ligands to new di ...

EPFL2023

Reprogramming G Protein-Coupled Receptor Structure, Function And Signaling By Computational Design

Dániel Kéri

G protein-coupled receptors (GPCRs) are 7-transmembrane alpha-helical integral membrane proteins on which cells heavily rely to receive information regarding their external environment. These receptors are able to transfer information to intracellular down ...

EPFL2021

Inositol pyrophosphates promote the interaction of SPX domains with the coiled-coil motif of PHR transcription factors to regulate plant phosphate homeostasis

Luciano Andres Abriata

Phosphorus is an essential nutrient taken up by organisms in the form of inorganic phosphate (Pi). Eukaryotes have evolved sophisticated Pi sensing and signaling cascades, enabling them to stably maintain cellular Pi concentrations. Pi homeostasis is regul ...

Nature Research2021

Molecular physiology of bile acid signaling in health, disease, and aging

Kristina Schoonjans, Alessia Perino, Hadrien Charles Edouard Demagny, Laura Alejandra Velazquez Villegas

Over the last two decades, bile acids (BAs) have become established as important signaling molecules that enable fine-tuned inter-tissue communication from the liver, their site of production, over the intestine, where they are modified by the gut microbio ...

2021

Post-translational regulation of neuronal differentiation

Jaipreet Singh Loomba

Glycosphingolipids (GSLs) are amphipathic lipid moieties that make up only 3% of the total lipid content of the cell and are almost exclusively expressed at the Plasma Membrane(PM). They are key drivers of signalling hotspots known as â lipid-raftsâ as ...

EPFL2021

Engineered Extracellular Matrices with Integrated Wireless Microactuators to Study Mechanobiology

Mahmut Selman Sakar, Erik Mailand, Nikolaos Bouklas, Fazil Emre Uslu

Mechanobiology explores how forces regulate cell behaviors and what molecular machinery are responsible for the sensing, transduction, and modulation of mechanical cues. To this end, probing of cells cultured on planar substrates has served as a primary ex ...

Wiley2021

Co-regulation of endothelial and myogenic cell fates through intercellular crosstalk in skeletal muscle

Umji Lee

Skeletal muscle is one of the most dynamic organs in the human body, which has a vigorous potential to regenerate and adapt to environmental changes. Depending on environments, skeletal muscle enables essential life activities to survive by controlling mov ...

EPFL2021

Excitation states of metabolic networks predict dose-response fingerprinting and ligand pulse phase signalling

Pierre Magistretti, Henry Markram, Felix Schürmann, Daniel Keller, Jay Coggan

With a computational model of energy metabolism in an astrocyte, we show how a system of enzymes in a cascade can act as a functional unit of interdependent reactions, rather than merely a series of independent reactions. These systems may exist in multipl ...

2020

Receptor-independent modulation of cAMP-dependent protein kinase and protein phosphatase signaling in cardiac myocytes by oxidizing agents

Sonia Donzelli

The contraction and relaxation of the heart is controlled by stimulation of the beta 1-adrenoreceptor (AR) signaling cascade, which leads to activation of cAMP-dependent protein kinase (PKA) and subsequent cardiac protein phosphorylation. Phosphorylation i ...

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC2020

A novel culture method that sustains ER alpha signaling in human breast cancer tissue microstructures

Cathrin Brisken, Georgios Sflomos

Background Estrogen receptor alpha (ER alpha) signaling is a defining and driving event in most breast cancers; ER alpha is detected in malignant epithelial cells of 75% of all breast cancers (classified as ER-positive breast cancer) and, in these cases, E ...

2020

Regulation of adenylyl cyclase 5 in striatal neurons confers the ability to detect coincident neuromodulatory signals

Ursula Röthlisberger, Siri Camee van Keulen, Daniele Narzi, Paolo Carloni

Author summary Adenylyl cyclases (ACs) are enzymes that can translate extracellular signals into the intracellular molecule cAMP, which is thus a 2nd messenger of extracellular events. The brain expresses nine membrane-bound AC variants, and AC5 is the dom ...

2019

Proteomics and Beyond: Cell Decision-Making Shaped by Reactive Electrophiles

Yimon Aye, Xuyu Liu

Revolutionary proteomic strategies have enabled rapid profiling of the cellular targets of electrophilic small molecules. However, precise means to directly interrogate how these individual electrophilic modifications at low occupancy functionally reshape ...

2019

High-throughput cryogenic spectroscopy for glycan analysis

Thomas Rizzo, Ahmed Ben Faleh, Stephan Warnke, Valeriu Scutelnic

A method for analyzing a plurality of molecules with cryogenic vibrational spectroscopy including the steps of providing a packet of molecules in a ionized form, injecting the packet into an ion mobility section, spatially separating the ions of the packet ...

2019

Mechanistic insights into AMP-activated protein kinase-dependent gene expression

Caterina Collodet

AMP-activated protein kinase (AMPK) is a fundamental enzyme that controls energy homeostasis, through orchestrating the cellular response to a reduction in energy availability. Under conditions of cellular energy stress AMPK senses the decrease in ATP leve ...

EPFL2019

Computational design of G Protein-Coupled Receptor allosteric signal transductions

Patrick Daniel Barth, Dániel Kéri

Membrane receptors sense and transduce extracellular stimuli into intracellular signaling responses but the molecular underpinnings remain poorly understood. We report a computational approach for designing protein allosteric signaling functions. By combin ...

2020