A5058227744- Optimization and Search Problems
- Computational Geometry and Mesh Generation
- Robotics and Sensor-Based Localization
- Robotic Path Planning Algorithms
- CRISPR and Genetic Engineering
- Auction Theory and Applications
- Single-cell and spatial transcriptomics
- Malaria Research and Control
- RNA modifications and cancer
- Machine Learning and Algorithms
- Algorithms and Data Compression
- Data Management and Algorithms
- Drug Transport and Resistance Mechanisms
- Advanced Bandit Algorithms Research
- Advanced Numerical Analysis Techniques
- Genomics and Phylogenetic Studies
- RNA Research and Splicing
- Microbial Natural Products and Biosynthesis
- Parasites and Host Interactions
- RNA and protein synthesis mechanisms
- Neurogenetic and Muscular Disorders Research
- Cell Image Analysis Techniques
- Optimization and Packing Problems
- Extracellular vesicles in disease
- Digital Image Processing Techniques
Novartis (Switzerland)
2016-2025
Novartis Institutes for BioMedical Research
2012-2022
KU Leuven
2010
University of Fribourg
1991-2005
University of Freiburg
1994-2003
Inform (Germany)
1999-2001
Ludwig-Maximilians-Universität München
1997
Western University
1995
Human organoids recapitulating the cell-type diversity and function of their target organ are valuable for basic translational research. We developed light-sensitive human retinal with multiple nuclear synaptic layers functional synapses. sequenced RNA 285,441 single cells from these at seven developmental time points periphery, fovea, pigment epithelium choroid light-responsive adult retinas, performed histochemistry. Cell types in matured vitro to a stable "developed" state rate similar...
With renewed calls for malaria eradication, next-generation antimalarials need be active against drug-resistant parasites and efficacious both liver- blood-stage infections. We screened a natural product library to identify inhibitors of Plasmodium falciparum blood- liver-stage proliferation. Cladosporin, fungal secondary metabolite whose target mechanism action are not known any species, was identified as having potent, nanomolar, antiparasitic activity blood liver stages. Using postgenomic...
RNA-sequencing (RNA-seq) has emerged as one of the most sensitive tool for gene expression analysis. Among library preparation methods available, standard poly(A) + enrichment provides a comprehensive, detailed, and accurate view polyadenylated RNAs. However, on samples suboptimal quality ribosomal RNA depletion exon capture have recently been reported better alternatives. We compared first time three commercial Illumina kits (TruSeq Stranded mRNA, TruSeq Ribo-Zero rRNA Removal, Access)...
Translation initiation is an emerging target in oncology and neurobiology indications. Naturally derived synthetic rocaglamide scaffolds have been used to interrogate this pathway; however, there uncertainty regarding their precise mechanism(s) of action. We exploited the genetic tractability yeast define primary effect both a natural cellular context characterized molecular using biochemical studies silico modeling. Chemogenomic profiling mutagenesis identified eIF (eukaryotic Initiation...
Abstract Fibrosis is characterized by the excessive production of collagen and other extracellular matrix (ECM) components represents a leading cause morbidity mortality worldwide. Previous studies nonalcoholic steatohepatitis (NASH) with fibrosis were largely restricted to bulk transcriptome profiles. Thus, our understanding this disease limited an incomplete characterization liver cell types in general hepatic stellate cells (HSCs) particular, given that activated HSCs are major fibrogenic...
We present FLASH-seq (FS), a full-length single-cell RNA sequencing (scRNA-seq) method with increased sensitivity and reduced hands-on time compared to Smart-seq3. The entire FS protocol can be performed in ~4.5 hours, is simple automate easily miniaturized decrease resource consumption. also use unique molecular identifiers (UMIs) for molecule counting while displaying strand-invasion artifacts. will especially useful characterizing gene expression at high resolution across multiple samples.
Plasmodium liver hypnozoites, which cause disease relapse, are widely considered to be the last barrier towards malaria eradication. The biology of this quiescent form parasite is poorly understood hinders drug discovery. We report a comparative transcriptomic dataset replicating schizonts and dormant hypnozoites relapsing cynomolgi. Hypnozoites express only 34% physiological pathways, while 91% expressed in schizonts. Few known targets parasites, but pathways involved microbial dormancy,...
A new cyclic decadepsipeptide was isolated from Chaetosphaeria tulasneorum with potent bioactivity on mammalian and yeast cells. Chemogenomic profiling in S. cerevisiae indicated that the Sec61 translocon, machinery for protein translocation membrane insertion at endoplasmic reticulum, is target. The profiles were similar to those of heptadepsipeptides a distinct chemotype (HUN-7293/cotransin) had previously been shown inhibit cotranslational translocon. Unbiased, genome-wide mutagenesis...
We develop CellSIUS (Cell Subtype Identification from Upregulated gene Sets) to fill a methodology gap for rare cell population identification scRNA-seq data. outperforms existing algorithms specificity and selectivity types their transcriptomic signature in synthetic complex biological Characterization of human pluripotent differentiation protocol recapitulating deep-layer corticogenesis using reveals unrecognized complexity stem cell-derived cellular populations. enables novel populations...
Relapses of Plasmodium dormant liver hypnozoites compromise malaria eradication efforts. New radical cure drugs are urgently needed, yet the vast gap in knowledge hypnozoite biology impedes drug discovery. We previously unraveled transcriptome 6 to 7 day-old P. cynomolgi stages, highlighting pathways associated with dormancy (Voorberg-van der Wel et al., 2017). now extend these findings by profiling 9 10 stage parasites, thus revealing for first time maturation over time. Although...
Genome-wide CRISPR-Cas9 dropout screens can identify genes whose knockout affects cell viability. Recent CRISPR detected thousands of essential required for cellular survival and key processes; however discovering novel lineage-specific genetic dependencies from the many hits still remains a challenge. To assess whether help cancer dependencies, we screened two human lines carrying known distinct oncogenic mutations using genome-wide sgRNA library. We found that gRNA targeting driver...
Abstract Droplet-based single-cell omics, including RNA sequencing (scRNAseq), CRISPR perturbations (e.g., CROP-seq), and protein transcriptomic profiling (CITE-seq) hold great promise for comprehensive cell genetic screening at the resolution. However, these technologies suffer from substantial noise, among which ambient signals present in suspension may be predominant source. Current models to address this issue are highly technology-specific relatively scRNAseq-centric. while a universal...
ABSTRACT High-throughput phenotypic screening against the yeast Saccharomyces cerevisiae revealed a series of triazolopyrimidine-sulfonamide compounds with broad-spectrum antifungal activity, no significant cytotoxicity, and low protein binding. To elucidate target this series, we have applied chemogenomic profiling approach using S. deletion collection. All yielded highly similar profiles that suggested acetolactate synthase (Ilv2p, which catalyzes first common step in branched-chain amino...
Abstract Chemogenomic profiling is a powerful and unbiased approach to elucidate pharmacological targets the mechanism of bioactive compounds. Until recently, genome-wide, high-resolution experiments this nature have been limited fungal systems due lack mammalian genome-wide deletion collections. With example novel nicotinamide phosphoribosyltransferase (NAMPT) inhibitor, we demonstrate that CRISPR/Cas9 system enables generation transient homo- heterozygous libraries allows for...
The quantification of transcriptomic features is the basis analysis RNA-seq data. We present an integrated alignment workflow and a simple counting-based approach to derive estimates for gene, exon exon–exon junction expression. In contrast previous approaches, EQP takes into account only reads whose pattern agrees with splicing interest. This leads improved gene expression as well generation counts that allow disambiguating between overlapping exons. Unlike other methods quantify skipped...
Abstract Biosynthesis of glycosylphosphatidylinositol (GPI) is required for anchoring proteins to the plasma membrane, and essential integrity fungal cell wall. Here, we use a reporter gene-based screen in Saccharomyces cerevisiae discovery antifungal inhibitors GPI-anchoring proteins, identify oligocyclopropyl-containing natural product jawsamycin (FR-900848) as potent hit. The compound targets catalytic subunit Spt14 (also referred Gpi3) UDP-glycosyltransferase, first step GPI...
Abstract Summary: Endeavour is a tool that detects the most promising genes within large lists of candidates with respect to biological process interest and by combining several genomic data sources. We have benchmarked using 450 pathway maps 826 disease marker sets from MetaCoreTM GeneGo, Inc. containing total 9911 12 432 genes, respectively. obtained an area under receiver operating characteristic curves 0.97 for 0.91 gene sets. These results indicate can be used efficiently prioritize...