A5082628754- Chemical Synthesis and Analysis
- Virus-based gene therapy research
- Receptor Mechanisms and Signaling
- Advanced Fluorescence Microscopy Techniques
- Digital Holography and Microscopy
- Cell Image Analysis Techniques
- Neuropeptides and Animal Physiology
- CAR-T cell therapy research
- Cytomegalovirus and herpesvirus research
- Diabetic Foot Ulcer Assessment and Management
- Digital Imaging for Blood Diseases
- Erythrocyte Function and Pathophysiology
- Herpesvirus Infections and Treatments
- Advanced biosensing and bioanalysis techniques
- Cancer therapeutics and mechanisms
- Click Chemistry and Applications
- Blood properties and coagulation
- Immunotherapy and Immune Responses
- Bacterial Genetics and Biotechnology
- Lipid Membrane Structure and Behavior
- Innovative Microfluidic and Catalytic Techniques Innovation
- Microfluidic and Bio-sensing Technologies
- Bacterial biofilms and quorum sensing
- Computational Drug Discovery Methods
- Antimicrobial Peptides and Activities
École Polytechnique Fédérale de Lausanne
2015-2024
Screen
2020
Charles Humbert 8
2020
University of Basel
2013
University of Neuchâtel
2004
École Supérieure de Biotechnologie de Strasbourg
2000
Centre National de la Recherche Scientifique
1999-2000
Ono Pharmaceutical (United States)
1999
Inserm
1999
Biogen (Switzerland)
1988-1989
Different chemical methods used to attach oligonucleotides by their 5′-end on a glass surface were tested in the framework of solid phase PCR where surface-bound instead freely-diffusing primers are amplify DNA. Each method was first evaluated for its capacity provide high coverage essentially attached via 5′-specific linkage that satisfyingly withstands conditions and leaves 3′-ends available DNA polymerase activity. The best results obtained with 5′-thiol-modified amino-silanised slides...
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 of new family 3′-OH unprotected cleavable fluorescent and their evaluation as for high-throughput SBS strategies. In this first version, all four modified nucleotides bearing disulfide Alexa Fluor® 594 dye were assayed ability to act stop incorporation next labeled base. Their use in leaded...
We introduce a label-free technology based on digital holographic microscopy (DHM) with applicability for screening by imaging, and we demonstrate its capability cytotoxicity assessment using mammalian living cells. For this first high content compatible application, automatized microscope image acquisition of cells commercially available 96-well plates. Data generated through both DHM imaging fluorescence-based methods were in good agreement cell viability identification Z'-factor close to...
A powerful chemical modification procedure has been developed to define determinants of DNA recognition by the p50 subunlt NF-xB. Differential labelling with [14C] iodoacetate Identified a conserved cystelne residue, Cys62, that was protected from presence an ollgonucleotide containing specific site protein. To determine Importance this each cysteines in changed serine and binding properties mutant proteins determined. Scatchard analysis Indicated C62S bound its 10-fold larger dissociation...
A general method for understanding the mechanisms of ligand recognition and activation G protein-coupled receptors has been developed. study ligand-receptor interactions in prototypic seven-transmembrane neurokinin-2 receptor (NK2) using this fluorescence-based approach is presented. fluorescent unnatural amino acid was introduced at known sites into NK2 by suppression UAG nonsense codons with aid a chemically misacylated synthetic tRNA specifically designed incorporation acids during...
Digital Holographic Microscopy (DHM) is a label-free imaging technique allowing visualization of transparent cells with classical cell culture plates. The quantitative DHM phase contrast image provided related both to the intracellular refractive index and thickness. able distinguish cellular morphological changes on two representative lines (HeLa H9c2) when treated doxorubicin chloroquine, cytotoxic compounds yielding distinct phenotypes. We analyzed parameters linked morphology content in...
Red blood cells collected in citrate-phosphate-dextrose can be stored for up to 42 days at 4 °C saline-adenine-glucose-mannitol additive solution. During this controlled, but nevertheless artificial, ex vivo ageing, red accumulate lesions that reversible or irreversible upon transfusion. The aim of the present study is follow several parameters reflecting cell metabolism, antioxidant defences, morphology and membrane dynamics during storage.Five erythrocyte concentrates were followed weekly...
Endemic human coronaviruses (hCoVs) 229E and OC43 cause respiratory disease with recurrent infections, while severe acute syndrome (SARS)-CoV-2 spreads across the world impact on health societies. Here, we report an image-based multicycle infection procedure α-coronavirus hCoV-229E-eGFP in arrayed chemical library screen of 5440 clinical preclinical compounds. Toxicity counter selection challenge β-coronaviruses SARS-CoV-2 tissue culture airway epithelial explant cultures (HAEEC) identified...
Abstract Macrocycles have excellent potential as therapeutics due to their ability bind challenging targets. However, generating macrocycles against new targets is hindered by a lack of large macrocycle libraries for high-throughput screening. To overcome this, we herein established combinatorial approach tethering myriad chemical fragments peripheral groups structurally diverse macrocyclic scaffolds in fashion, all at picomole scale nanoliter volumes using acoustic droplet ejection...
Phosphomannose isomerase catalyses the interconversion of fructose‐6‐ P and mannose‐6‐ has a critical role in supply d ‐mannose derivatives required for many eukaryotic glycosylation reactions. Three classes enzymes possessing phosphomannose‐isomerase activity have been identified bacteria lower eukaryotes. We purified human phosphomannose to homogeneity from placental tissue. Protein sequence information obtained internal fragments protein was used design degenerate oligonucleotides which...
Advances in treatment strategies together with an earlier diagnosis have considerably increased the average survival of cancer patients over last four decades. Nevertheless, despite growing number new antineoplastic agents introduced each year, there is still no adequate therapy for problematic malignancies such as pancreatic, lung and stomach cancers. Consequently, it important to ensure that existing drugs used treat other types cancers, potentially diseases, are not overlooked when...
Compounds tested during drug development may have adverse effects on the heart; therefore all new chemical entities to undergo extensive preclinical assessment for cardiac liability. Conventional intensity-based imaging techniques are not robust enough provide detailed information cell structure and captured images result in low-contrast, especially with semi-transparent or transparent feature, which would affect analysis. In this paper we show, first time, that digital holographic...
An efficient cyclization reaction allows for screening of large macrocycle libraries and yields a potent thrombin inhibitor.
We propose methods to quantitatively calculate the fluctuation rate of red blood cells with nanometric axial and millisecond temporal sensitivity at single-cell level by using time-lapse holographic cell imaging. For this quantitative analysis, membrane fluctuations (CMFs) were measured for RBCs stored different storage times. Measurements taken over whole both ring dimple sections separately. The measurements show that healthy maintain their discocyte shape become stiffer time. correlation...
Ligand recognition of the NK1 receptor (substance P receptor) by peptide agonist and non-peptide antagonist has been investigated compared use fluorescent ligands spectrofluorometric methods. Analogues substance (SP) labeled with environment-sensitive group 5-dimethylaminonaphthalene-1-sulfonyl (dansyl) at either position 3, 8, or 11 fluorescein the<i>N</i> <sup>α</sup> were synthesized characterized. Peptides modified α-amino positions 3 conserved a relatively good affinity for agonistic...
This work presents a simple microfluidic device with an integrated thin-film heater for studies of DNA hybridization kinetics and double-stranded melting temperature measurements. The heating characteristics the were evaluated novel, noninvasive indirect technique using molecular beacons as probes inside reaction chambers. is first in which thermal dehybridization surface-bound oligonucleotides was performed measurement temperatures +/- 1 degrees C precision. Surface modification...
Drug combinations are extensively used to treat cancer and often selected according complementary mechanisms. Here, we describe a cell-based high-throughput screening assay for identification of synergistic between broadly applied platinum-based chemotherapeutics drugs from library composed 1280 chemically pharmacologically diverse (mostly FDA approved) compounds. The was performed on chemoresistant cell lines derived lung (A549) pancreatic (PANC-1) carcinoma, where combination regimens...
In vitro differentiating adipocytes are sensitive to liquid manipulations and have the tendency float. Assessing adipocyte differentiation using current microscopy techniques involves cell staining washing, while flow cytometry retrieval in suspension. These methods induce biases, difficult reproduce, involve tedious optimizations. this study, we present digital holographic (DHM) as a label-free, nonperturbing means quantify lipid droplets robust medium- high-throughput manner. Taking...