Publications associées à Drug discovery through stem cell-based organoid models

Drug Screening in C. elegans to identify new pharmacological mitochondrial stress inducers

Mitochondria are essential organelles participating in numerous cellular functions, including energy harvesting, regulation of homeostasis and apoptosis. Changes in mitochondrial number, morphology, and function not only impact cellular metabolism but also ...

EPFL2024

Deconvolution of ex-vivo drug screening data and bulk tissue expression predicts the abundance and viability of cancer cell subpopulations

Alexandre Coudray

Ex-vivo drug sensitivity screening (DSS) allows the prediction of cancer treatment effectiveness in a personalized fashion. However, it only provides a readout on mixtures of cells, potentially occulting important information on clinically relevant cell su ...

EPFL2023

Methods for high-throughput synthesis and screening of peptide libraries

Zsolt Bognár

Macrocycles provide an attractive modality for drug development but the identification of ligands to targets of interest is hindered by the lack of large macrocyclic compound libraries for high-throughput screening. A strategy to efficiently synthesize lar ...

EPFL2024

Improved microfluidic transcriptome based screening methods

Christoph Merten, Leonie Kolmar, Xiaoli Ma, Hongxing Hu

The invention provides microfluidic screening systems for the identification of compounds or compositions influencing cellular transcriptomes. The invention is predicated upon taking into account differences in newly synthesized mRNA in contrast to so call ...

2024

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

Bioengineering functional organoid models across scales

Tania Hübscher

The last two decades have seen the development of organoid models for many different tissues and organs. Organoids are three-dimensional organ-mimetics derived from stem or progenitor cells comprising various specialized cell types, resembling the architec ...

EPFL2024

Cyclic Peptides for Drug Development

Christian Heinis, Xinjian Ji, Alexander Lund Nielsen

Cyclic peptides are fascinating molecules abundantly found in nature and exploited as molecular format for drug development as well as other applications, ranging from research tools to food additives. Advances in peptide technologies made over many years ...

Wiley-VCH Verlag GmbH2024

The predictive capacity of in vitro preclinical models to evaluate drugs for the treatment of retinoblastoma

Paul Joseph Dyson, Irina Sinenko, Roland Christopher Turnell-Ritson

Retinoblastoma is a rare childhood cancer of the eye. Of the small number of drugs are used to treat retinoblastoma, all have been repurposed from drugs developed for other conditions. In order to find drugs or drug combinations better suited to the improv ...

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD2023

A multi-reservoir extruder for time-resolved serial protein crystallography and compound screening at X-ray free-electron lasers

Camila Bacellar Cases Da Silveira, Christoph Bostedt

Serial crystallography at X-ray free-electron lasers (XFELs) permits the determination of radiation-damage free static as well as time-resolved protein structures at room temperature. Efficient sample delivery is a key factor for such experiments. Here, we ...

Nature Portfolio2023

Nanomole-scale photochemical thiol-ene chemistry for high-throughput late-stage diversification of peptide macrocycles

Mischa Schüttel, Alexander Lund Nielsen, Mark Daniel Nolan

The photochemical thiol-ene reaction is an efficient method for rapid and chemoselective formation of thioether linkages under mild conditions. It has found widespread use in small-molecule synthesis as well as peptide and protein chemistry. While high-thr ...

WILEY2023

Label-free plasmonic microarray for multiplexed analysis of cells and tumor organoids

Yen-Cheng Liu

Investigating the dynamic activities of protein expression and signaling in living organisms is a crucial focus of intense research aimed at elucidating the processes that underlie disease progression and improving treatments and drug development. Resolvin ...

EPFL2023

Effective Inhibition of TDP-43 Aggregation by Native State Stabilization

Hilal Lashuel, Lixin Yang, Yllza Jasiqi

Preventing the misfolding or aggregation of transactive response DNA binding protein with 43 kDa (TDP-43) is the most actively pursued disease-modifying strategy to treat amyotrophic lateral sclerosis and other neurodegenerative diseases. In this work, we ...

Wiley-VCH Verlag GmbH2024

Optimised three-dimensional in vitro retinoblastoma models tailored for drug discovery and clinical translatability

Irina Sinenko

Retinoblastoma, while relatively rare, stands as the most prevalent intraocular cancer. In Switzerland, the survival rate approaches 100%, but it drops to less than 50% in low-income countries. The current treatment options for retinoblastoma rely on a lim ...

EPFL2023

Method for hormone or drug screening in a tissue sample

Cathrin Brisken, Yueyun Zhang, Christoph Merten

The present invention relates to a method for analyzing cellular responsiveness to hormones or drags in a tissue sample based on an alginate-based 3D ex vivo culture system for normal and malignant tissue microstructures and uses thereof. ...

2023

Automated Dual-Mode Cell Monitoring To Simultaneously Explore Calcium Dynamics and Contraction-Relaxation Kinetics within Drug-Treated Stem Cell-Derived Cardiomyocytes

Gerardo Turcatti, Pierre Marquet, Benjamin Rappaz, Bokyoung Kim

This manuscript proposes a new dual-mode cell imaging system for studying the relationships between calcium dynamics and the contractility process of cardiomyocytes derived from human-induced pluripotent stem cells. Practically, this dual-mode cell imaging ...

AMER CHEMICAL SOC2023

Bioengineering human mini-intestines with in vivo-like complexity and function

Olga Mitrofanova

Biological research heavily relies on the use of animal models, which has made it difficult to answer specific questions about human biology and disease. However, with the advent of human organoids - miniature versions of tissues generated in 3D human stem ...

EPFL2023

Multimodal characterization of murine gastruloid development

Matthias Lütolf, Raphaël Ortiz, Stefano Davide Vianello, Alexandre Gauthier Aurèle Mayran

Gastruloids are 3D structures generated from pluripotent stem cells recapitulating fundamental principles of embryonic pattern formation. Using single-cell genomic analysis, we provide a resource mapping cell states and types during gastruloid development ...

CELL PRESS2023

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

Philippe Renaud, Shahin Bonakdar, Leila Montazeri, Zahrasadat Ghazali

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

Disruption of stem cell niche-confined R-spondin 3 expression leads to impaired hematopoiesis

Freddy Radtke, Ute Koch, Jialin Zhang, Soufiane Boumahdi

Self-renewal and differentiation of stem and progenitor cells are tightly regulated to ensure tissue homeostasis. This regulation is enabled both remotely by systemic circulating cues, such as cytokines and hormones, and locally by various niche-confined f ...

ELSEVIER2023

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