Publications de Gerardo Turcatti

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A fluorescent unnatural amino acid was introduced biosynthetically at known sites into the G protein-coupled neurokinin (tachykinin) NK2 receptor by suppression of UAG nonsense codons with the aid of a chem. misacylated synthetic tRNA specifically designed for the incorporation of unnatural amino acids during heterologous expression in Xenopus oocytes. A systematic UAG-scanning mutagenesis in NK2 extra- or intracellular loops and proximal transmembrane domains established that read-through at some UAG sites

Stem-cell-derived epithelial organoids are routinely used for the biological and biomedical modelling of tissues. However, the complexity, lack of standardization and quality control of stem cell culture in solid extracellular matrices hampers the routine ...

Digital Holographic Microscopy (DHM) is a label-free imaging technique allowing visualization of transparent cells with classical imaging cell culture plates. The quantitative DHM phase contrast image provided is related both to the intracellular refractiv ...

Summary Translation inhibitors are invaluable for probing ribosome function and therapeutic applications, but systematic discovery in human systems is limited by the lack of scalable, screening-compatible cell-free platforms. Here, we establish a robust high-throughput screening using human lysates that bypasses cellular cytotoxic effects. After screening ∼28, 000 small molecules, we identified known and novel translation inhibitors, including NT-2, a trichothecene mycotoxin produced by the pathogenic Fusar

Retinoblastoma (RB) management often involves the combination of chemotherapeutic agents (e.g., carboplatin and etoposide) and techniques (e.g., chemotherapy and thermotherapy). Chemoresistance and relapse, as well as systemic and ocular toxicities of current retinoblastoma chemotherapeutics necessitate the implementation of alternative drugs. Fewer resources and concern for pediatric cancer hinder drug discovery and development in an effective way. To overcome the obstacle, a drug repurposing strategy with

The tricarboxylate reagent benzene-1,3,5-triacetic acid (BTA) was used to attach 5'-aminated DNA primers and templates on an aminosilanized glass surface for subsequent generation of DNA colonies by in situ solid-phase amplification. We have characterized ...

Cellular assays using label-free Digital Holographic Microscopy (DHM) have been previously validated for cell viability assays in a drug screening context. Our automated DHM system allows performing fast and cost-effective screening assays for a wide range of applications for monitoring cell morphological changes and cell movements upon interaction with interfering compounds. In addition to these classic phenotypic assays, it has been demonstrated that target-based cellular assays can also be addressed by D

A review with 6 refs. of the authors' work in developing a biophys. technique to investigate the structure, function and dynamics of membrane receptors. A fluorescence-based approach has been developed and applied to the prototypic G protein-coupled receptor NK2. A fluorescent unnatural amino acid was introduced at known sites into NK2 by suppression of nonsense codons with the aid of a chem. misacylated synthetic tRNA specifically designed for the incorporation of unnatural amino acids during expression in

We use quantitative phase digital holographic microscopy (QP-DHM) to image and quantify the beating movement of cardiomyocytes, derived from induced pluripotent stem cells (iPSCs), in control and drug-treated conditions. The development of an analysis algo ...

Glutathione S-transferase P1-1 (GST P1) is an important drug target as it is implicated in drug resistance. GST P1-1 inhibitors are typically non-productive analogues of glutathione which covers broad chemical space; hence it is likely that several clinica ...

Fluorescent 2'-deoxynucleotides containing a protecting group at the 3'-O-position are reversible terminators enabling array-based DNA sequencing by synthesis (SBS) approaches. Herein, we describe the synthesis of a new family of 3'-OH unprotected cleavabl ...

Compounds tested during drug development may have adverse effects on the heart; therefore all new chemical entities have to undergo extensive preclinical assessment for cardiac liability. Conventional intensity-based imaging techniques are not robust enoug ...

DNA sequence information underpins genetic research, enabling discoveries of important biological or medical benefit. Sequencing projects have traditionally used long (400-800 base pair) reads, but the existence of reference sequences for the human and man ...

Macrocyclic compounds are an attractive modality for drug development, but the limited availability of large, structurally diverse macrocyclic libraries hampers the discovery of leads. Here, we describe the discovery of efficient macrocyclization reactions ...

Indoleamine 2,3-dioxygenase 1 (IDO1) is a key regulator of immune responses and therefore an important therapeutic target for the treatment of diseases that involve pathological immune escape, such as cancer. Here, we describe a robust and sensitive high-t ...

Background - Thequalityof red blood cells (RBCs) stored in red cell concentrates (RCCs) is influenced by processing, storage and donor characteristics, and can have a clinical impact on transfused patients. To evaluate RBC properties and their potential im ...

The Wnt pathway, which controls crucial steps of the development and differentiation programs, has been proposed to influence lipid storage and homeostasis. In this paper, using an unbiased strategy based on high-content genome-wide RNAi screens that monit ...

An increase of oxygen saturation within blood bags and metabolic dysregulation occur during storage of red blood cells (RBCs). It leads to the gradual exhaustion of RBC antioxidant protective system and, consequently, to a deleterious state of oxidative st ...

Stress response pathways rely on coordinated gene expression regulation. In the endoplasmic reticulum, the unfolded protein response plays an important role in maintaining the homeostasis of protein folding and processing. A chemigenetic reporter assay is developed that allows monitoring of BiP/GRP78 expression, a key regulator of the unfolded protein response. The system is based on the coexpression of the self‐labeling protein HaloTag via an internal ribosome entry site. HaloTag allows for flexibility in

The Biomolecular Screening Facility (BSF) is a multidisciplinary laboratory created in 2006 at the Ecole Polytechnique Federale de Lausanne (EPFL) to perform medium and high throughput screening in life sciences-related projects. The BSF was conceived and ...

Gerardo Turcatti

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Fluorescent labeling of NK2 receptor at specific sites in vivo and fluorescence energy transfer analysis of NK2 ligand-receptor complexes

High-throughput automated organoid culture via stem-cell aggregation in microcavity arrays

Digital holographic microscopy: a quantitative label-free microscopy technique for phenotypic screening

A human cell-free translation screen identifies the NT-2 mycotoxin as a ribosomal peptidyl transferase inhibitor

High-throughput screening of drug libraries identifies a new synergistic drug combination for the treatment of retinoblastoma

BTA, a novel reagent for DNA attachment on glass and efficient generation of solid-phase amplified DNA colonies

Digital Holographic Imaging for Label-Free Phenotypic Profiling, Cytotoxicity, and Chloride Channels Target Screening

Probing ligand-receptor recognition in G protein-coupled receptors through biosynthetic incorporation of fluorescent amino acids at specific sites and measurement of distances by fluorescence energy transfer

Marker-Free Automatic Quantification of Drug-Treated Cardiomyocytes with Digital Holographic Imaging

Identification of glutathione transferase (GST P1) inhibitors via a high-throughput screening assay and implications as alternative treatment options for breast cancers

A new class of cleavable fluorescent nucleotides: synthesis and optimization as reversible terminators for DNA sequencing by synthesis

Automated multi-parameter measurement of cardiomyocytes dynamics with digital holographic microscopy

Accurate whole human genome sequencing using reversible terminator chemistry

Thiol-to-amine cyclization reaction enables screening of large libraries of macrocyclic compounds and the generation of sub-kilodalton ligands

Detailed analysis and follow-up studies of a high-throughput screening for indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors

In vitro-transfusional model for red-blood-cell study: the advantage of lowering hematocrit

Wnt directs the endosomal flux of LDL-derived cholesterol and lipid droplet homeostasis

Image- and Fluorescence-Based Test Shows Oxidant-Dependent Damages in Red Blood Cells and Enables Screening of Potential Protective Molecules

Two‐Color Timestamping of Gene Expression with a Chemigenetic Reporter System

Developing the Biomolecular Screening Facility at the EPFL into the Chemical Biology Screening Platform for Switzerland