Publications related to Phenotypic screening

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

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

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

Amélia Lalou

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

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

Christoph Bostedt, Camila Bacellar Cases Da Silveira

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

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

Method for hormone or drug screening in a tissue sample

Cathrin Brisken, Christoph Merten, Yueyun Zhang

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

Novel High-Throughput Fluorescence-Based Assay for the Identification of Nematocidal Compounds That Target the Blood-Feeding Pathway

Gerardo Turcatti, Marc Chambon, Anthony Marchand, Nicola Harris, Tiffany Babette Angélique Bouchery, Mati André Marie Moyat

Hookworm infections cause a neglected tropical disease (NTD) affecting ~740 million people worldwide, principally those living in disadvantaged communities. Infections can cause high morbidity due to their impact on nutrient uptake and their need to feed o ...

2022

Intestinal stem cells differentiation and its application in cancer therapy

Maxim Norkin

Colorectal cancer (CRC) is one of the deadliest cancers worldwide. Despite extensive research in the field, new therapies targeting CRC are in urgent need. CRC is a highly heterogeneous disease with high levels of intra- and inter-patient heterogeneity. Ca ...

EPFL2021

Monitoring alpha-synuclein oligomerization and aggregation using bimolecular fluorescence complementation assays: What you see is not always what you get

Hilal Lashuel, Nathan Alain Denis Riguet, Bryan Frey, Abdelrahman Mohammed Adel Elsaeed Mansour AlOkda

Bimolecular fluorescence complementation (BiFC) was introduced a decade ago as a method to monitor alpha-synuclein (alpha-syn) oligomerization in intact cells. Since then, several alpha-syn BiFC cellular assays and animal models have been developed based o ...

Wiley-Blackwell2021

Characterization of the Mercapturic Acid Pathway, an Important Phase II Biotransformation Route, in a Zebrafish Embryo Cell Line

Kristin Schirmer, Alena Tierbach

In view of the steadily increasing number of chemical compounds used in various products and applications, high-throughput toxicity screening techniques can help meeting the needs of 21st century risk assessment. Zebrafish (Danio rerio), especially its ear ...

AMER CHEMICAL SOC2020

Automated Platform for Long-Term Culture and High-Content Phenotyping of Single C. elegans Worms

Johan Auwerx, Martinus Gijs, Matteo Cornaglia, Laurent Mouchiroud, Rongrong Xiang, Elena Katsyuba, Hüseyin Baris Atakan

The nematode Caenorhabditis elegans is a suitable model organism in drug screening. Traditionally worms are grown on agar plates, posing many challenges for long-term culture and phenotyping of animals under identical conditions. Microfluidics allows for ' ...

Nature Research2019

A Universal Assay for Aminopeptidase Activity and Its Application for Dipeptidyl Peptidase-4 Drug Discovery

Gerardo Turcatti, Marc Chambon, Julien Bortoli Chapalay, Elena Goun, Jonathan Patrice Vesin, Arkadiy Bazhin, James William Collins

Aminopeptidases, such as dipeptidyl peptidase 4 (DPP-4, CD26), are potent therapeutic targets for pharmacological interventions because they play key roles in many important pathological pathways. To analyze amino-peptidase activity in vitro (including hig ...

AMER CHEMICAL SOC2019

A novel cell-based sensor detecting the activity of individual basic proprotein convertases

Daniel Constam, Karin Irmgard Löw, Stefan Kunz

The basic proprotein convertases (PCs) furin, PC1/3, PC2, PC5/6, PACE4, PC4, and PC7 are promising drug targets for human diseases. However, developing selective inhibitors remains challenging due to overlapping substrate recognition motifs and limited str ...

WILEY2019

Multimodal imaging and high-throughput image-processing for drug screening on living organisms on-chip

Michaël Unser, Johan Auwerx, Martinus Gijs, Matteo Cornaglia, Laurent Mouchiroud, Daniel Migliozzi, Virginie Sophie Uhlmann

A major step for the validation of medical drugs is the screening on whole organisms, which gives the systemic information that is missing when using cellular models. Caenorhabditis elegans is a soil worm that catches the interest of researchers who study ...

SPIE Society of Photo-optical Instrumentation Engineers2019

An optimized and validated 384-well plate assay to test platelet function in a high-throughput screening format

Nikolaos Stergiopoulos, Olivier Burri, Marc Chambon, Rodrigo Araujo Fraga Da Silva, Fabiana Pereira Da Costa Fraga, Julien Bortoli Chapalay, Augusto Martins Lima, Maiia Bragina

Despite significant advances in the treatment of cardiovascular diseases, antiplatelet therapies are still associated with a high risk of hemorrhage. In order to develop new drugs, methods to measure platelet function must be adapted for the high-throughpu ...

TAYLOR & FRANCIS INC2019

A microfluidic array for high-content screening at whole-organism resolution

Johan Auwerx, Martinus Gijs, Matteo Cornaglia, Laurent Mouchiroud, Daniel Migliozzi

A main step for the development and the validation of medical drugs is the screening on whole organisms, which gives the systemic information that is missing when using cellular models. Among the organisms of choice, Caenorhabditis elegans is a soil worm w ...

SPIE-INT SOC OPTICAL ENGINEERING2018

An ecotoxicological view on neurotoxicity assessment

Wolfgang Schulz

The numbers of potential neurotoxicants in the environment are raising and pose a great risk for humans and the environment. Currently neurotoxicity assessment is mostly performed to predict and prevent harm to human populations. Despite all the efforts in ...

SPRINGEROPEN2018

Microfluidic high-content phenotypic screening on a Caenorhabditis elegans model

Maria Cristina Letizia

Caenorhabditis elegans is a performant model system for studying human biological processes and diseases and for pre-clinical phenotyping screenings of compounds. Microfluidics has been instrumental in enabling C. elegans-based drug assays, facilitating th ...

EPFL2018

Semisynthetic Biosensors for the Quantification of Nicotinamide Adenine Dinucleotides in Live Cells

Olivier Vincent Sallin

Nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) are crucial redox cofactors regulating energy metabolism, reductive biosynthesis and the antioxidant defense system. Besides their role as redox cofactors, NAD(P ...

EPFL2018

Dynamic Nuclear Polarization of Long-Lived Nuclear Spin States in Methyl Groups

Geoffrey Bodenhausen, Aurélien Bornet, Sami Jannin, Basile Vuichoud, Daniele Mammoli, Arthur César Pinon, Gabriele Stevanato

We have induced hyperpolarized long-lived states in compounds containing C-13-bearing methyl groups by dynamic nuclear polarization (DNP) at cryogenic temperatures, followed by dissolution with a warm solvent. The hyper polarized methyl long-lived states g ...

Amer Chemical Soc2017

Using PyMOL as a platform for computational drug design

Shuguang Yuan, Zhenquan Hu

PyMOL, a cross-platform molecular graphics tool, has been widely used for three-dimensional (3D) visualization of proteins, nucleic acids, small molecules, electron densities, surfaces, and trajectories. It is also capable of editing molecules, ray tracing ...

Wiley2017