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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 ...

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Proliferation-driven mechanical compression induces signalling centre formation during mammalian organ development

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Localized sources of morphogens, called signalling centres, play a fundamental role in coordinating tissue growth and cell fate specification during organogenesis. However, how these signalling centres are established in tissues during embryonic developmen ...

Nature Portfolio2024

Accessible and highly observable gastrointestinal organoid model systems for studying host-pathogen interactions

Moritz Hofer

Traditional cell cultures have long been fundamental to biological research, offering an alternative to animal models burdened by ethical constraints and procedural intricacies, often lacking relevance to human physiology and disease. Moreover, their inabi ...

EPFL2024

Characterization of the gut-bone marrow axis through bile acid signaling

Alejandro Alonso Calleja

Communication between the intestine and other organs such as the lungs, brain or bones is mediated by several metabolites, like short-chain fatty acids or bile acids, that relay information about nutritional and microbiota status. Bile acids are endogenous ...

EPFL2024

Single-cell epigenomic reconstruction of developmental trajectories from pluripotency in human neural organoid systems

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Cell fate progression of pluripotent progenitors is strictly regulated, resulting in high human cell diversity. Epigenetic modifications also orchestrate cell fate restriction. Unveiling the epigenetic mechanisms underlying human cell diversity has been di ...

Nature Portfolio2024

S-acylation and lipid exchange at the ER-Golgi membrane contact sites regulate pathogen entry in human cells

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Cells have evolved endocytic pathways to internalize different molecules, to regulate intra-cellular communication and their interaction with external environment. Pathogens have co-evolved with cells to exploit these processes for infections. In particula ...

EPFL2024

Ultraviolet Superradiance from Mega-Networks of Tryptophan in Biological Architectures

Majed Chergui, Katrin Elisabeth Oberhofer

Networks of tryptophan (Trp)& horbar;an aromatic amino acid with strong fluorescence response & horbar;are ubiquitous in biological systems, forming diverse architectures in transmembrane proteins, cytoskeletal filaments, subneuronal elements, photorecepto ...

Amer Chemical Soc2024

Clinically compliant cryopreservation of differentiated retinal pigment epithelial cells

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Background aims: Age-related macular degeneration (AMD) is the most common cause of blindness in elderly patients within developed countries, affecting more than 190 million worldwide. In AMD, the retinal pigment epithelial (RPE) cell layer progressively d ...

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

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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

Engineered substrates incapable of induction of chondrogenic differentiation compared to the chondrocyte imprinted substrates

Philippe Renaud, Leila Montazeri

It is well established that surface topography can affect cell functions. However, finding a reproducible and reliable method for regulating stem cell behavior is still under investigation. It has been shown that cell imprinted substrates contain micro- an ...

IOP Publishing Ltd2023

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 ...

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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

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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

Programming of Multicellular Patterning with Mechano-Chemically Microstructured Cell Niches

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Multicellular patterning of stem-cell-derived tissue models is commonly achieved via self-organizing activities triggered by exogenous morphogenetic stimuli. However, such tissue models are prone to stochastic behavior, limiting the reproducibility of cell ...

WILEY2023

A single-cell-based characterization of mammalian adipose stem and progenitor cell heterogeneity and function

Pernille Yde Rainer

White adipose tissue (WAT) is a cellularly heterogeneous endocrine organ that not only serves as a reservoir for storing and releasing energy but also actively participates in metabolic homeostasis. Given the current rise in obesity and its associated como ...

EPFL2023

Neuronal migration prevents spatial competition in retinal morphogenesis

Martin Weigert

The concomitant occurrence of tissue growth and organization is a hallmark of organismal development(1-3). This often means that proliferating and differentiating cells are found at the same time in a continuously changing tissue environment. How cells ada ...

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Cross-anatomical single-cell definition and characterization of human adipose progenitor niche

Radiana Ferrero

Adipose tissue is a key metabolic and highly-dynamic organ whose dysregulation may cause clinical conditions of concern such as obesity and lipodystrophy. Its function varies based on the anatomy, in fact, visceral adipose tissue expansion carries a greate ...

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Low temperature and mTOR inhibition favor stem cell maintenance in human keratinocyte cultures

Kai Johnsson, Yann Barrandon, Thomas Michael Braschler, Ariane Rochat, Jean-Baptiste Bureau, Fahd Azzabi Zouraq, Johannes Alexander Mosig

Adult autologous human epidermal stem cells can be extensively expanded ex vivo for cell and gene therapy. Identifying the mechanisms involved in stem cell maintenance and defining culture conditions to maintain stemness is critical, because an inadequate ...

WILEY2023

Deciphering the molecular events leading to the global restoration of the chromatin landscape during mitotic exit

Silja Michelle Placzek

Two fundamental properties of embryonic stem cells (ESCs) are their ability to self-renew and differentiate into all somatic cell types. Maintenance of their identity faces major challenges when transitioning through mitosis, as most DNA-binding proteins a ...

EPFL2023

Species-specific regulation of XIST by the JPX/FTX orthologs

Olga Marie Louise Rosspopoff

X chromosome inactivation (XCI) is an essential process, yet it initiates with remarkable diversity in various mammalian species. XIST, the main trigger of XCI, is controlled in the mouse by an interplay of lncRNA genes (LRGs), some of which evolved concom ...

OXFORD UNIV PRESS2023