- Mycobacterium research and diagnosis
- Tuberculosis Research and Epidemiology
- Lanthanide and Transition Metal Complexes
- Metal complexes synthesis and properties
- Microbial Natural Products and Biosynthesis
- Autophagy in Disease and Therapy
- Legionella and Acanthamoeba research
- Computational Drug Discovery Methods
- Phagocytosis and Immune Regulation
- Metabolomics and Mass Spectrometry Studies
- Cellular transport and secretion
- Slime Mold and Myxomycetes Research
- Micro and Nano Robotics
- Protist diversity and phylogeny
- Ecosystem dynamics and resilience
- Enzyme Catalysis and Immobilization
- Vibrio bacteria research studies
- Genomics and Phylogenetic Studies
- Bacterial biofilms and quorum sensing
- Barrier Structure and Function Studies
- Cellular Mechanics and Interactions
- Calcium signaling and nucleotide metabolism
- Neuroinflammation and Neurodegeneration Mechanisms
- Antibiotic Resistance in Bacteria
- DNA and Nucleic Acid Chemistry
University of Geneva
2020-2024
University of Konstanz
2021
Cells are perpetually challenged by pathogens, protein aggregates or chemicals, that induce plasma membrane endolysosomal compartments damage. This severe stress is recognised and controlled the endosomal sorting complex required for transport (ESCRT) autophagy machineries, which recruited to damaged membranes either repair remove remnants. Yet, insight limited about how damage sensed effectors lead extensive tagging of organelles with signals, such as K63-polyubiquitin, recruitment removal...
The emergence of biochemically and genetically tractable host model organisms for infection studies holds the promise to accelerate pace discoveries related evolution innate immunity dissection conserved mechanisms cell-autonomous defenses. Here, we have used system Dictyostelium discoideum / Mycobacterium marinum apply a genome-wide transposon-sequencing experimental strategy reveal comprehensively which mutations confer fitness advantage or disadvantage during compare these similar...
Knowledge graph organization of metabolomic data provides a powerful tool to accelerate the discovery new therapeutic solutions against multidrug-resistant tuberculosis.
The rising threat of Multidrug-Resistant Tuberculosis (MDR-TB), caused by Mycobacterium tuberculosis (Mtb), underscores the urgent need for new therapeutic solutions to tackle challenge antibiotics resistance. current study utilized an innovative 3R infection model featuring amoeba Dictyostelium discoideum infected with marinum, serving as stand-ins macrophages and Mtb, respectively. This high-throughput phenotypic assay allowed evaluation more specific anti-infective activities that may be...
Dictyostelium discoideum amoebae feed by ingesting bacteria, then killing them in phagosomes. Ingestion and of different bacteria have been shown to rely on largely molecular mechanisms. One would thus expect that D. adapts its ingestion machinery when encountering bacteria. In this study, we investigated RNA sequencing if how respond the presence modifying their gene expression patterns. Each bacterial species analyzed induced a specific modification transcriptome. Bacteria such as Bacillus...
Tubercular Mycobacteria and Legionella pneumophila are the causative agents of potentially fatal respiratory diseases due to their intrinsic pathogenesis but also emergence antibiotic resistance that limits treatment options. The aim our study was explore antimicrobial activity a small ligand-based chemical library 1255 structurally diverse compounds. These compounds were screened in combination three assays, two monitoring intracellular growth pathogenic bacteria, Mycobacterium marinum L....
ABSTRACT This study evaluated the efficacy of a high-throughput Dictyostelium discoideum – Mycobacterium marinum Dd-Mm infection system by first benchmarking it against set antibiotics and second in screening library natural product (NP) derivatives for anti-infective activity intracellular (Mm). The observed no pyrazinamide Mm, consistent with known resistance patterns, confirmed other antibiotics, such as rifampicin bedaquiline, below defined antibacterial susceptibility breakpoints. From...
Introduction Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, remains a serious threat to human health worldwide and quest for new anti-tubercular drugs is an enduring demanding journey. Natural products (NPs) have played significant role in advancing drug therapy infectious diseases. Methods This study evaluated suitability high-throughput infection system composed host amoeba Dictyostelium discoideum (Dd) marinum (Mm), close relative Mtb, identify anti-infective...
ABSTRACT Mycobacterium tuberculosis , the causative agent of tuberculosis, is able to manipulate phagosome compartment in which it resides order establish a permissive replicative called -containing vacuole (MCV). marinum fish pathogen and close relative group, infect free-living amoeba professional phagocyte Dictyostelium discoideum its maturation. By using this host-pathogen model system, we have established an innovative process isolate MCVs. This procedure allowed us M. -MCV at 1, 3 6...
Antibiotics resistance is a clear threat to the future of current tuberculosis treatments like rifampicin, prompting need for new treatment options in this field. While plants can offer plethora chemical diversity their constitutive natural products tackle issue, finding potentially bioactive compounds them has not always proven be that simple. Classical bioactivity-guided fractionation approaches are still trendy, but they bear significant shortfalls, time-consuming nature as well...
Nature has always been an interesting source of chemical diversity for the search molecules therapeutic interest. Here we showed how large plant extract libraries can be transformed into a library. This library could then efficiently used to isolate unreported bioactivity advance our knowledge on disease treatments.
Summary Tuberculosis is among the world’s deadliest diseases, causing approximately 2 million deaths annually. The urgent need for new antitubercular drugs has been intensified by rise of drug-resistant strains. Despite recent advancements, most hits identified through traditional target-based screening exhibit limited efficacy in vivo . Consequently, there a growing demand whole-cell-based approaches that directly utilize host-pathogen systems. Dictyostelium discoideum – Mycobacterium...
ABSTRACT Cells are perpetually challenged by pathogens, protein aggregates or chemicals, that induce plasma membrane endolysosomal compartments damage, recognised as severe stress and controlled downstream the endosomal sorting complex required for transport (ESCRT) autophagy machineries recruited to damaged membranes either repair remove remnants. Yet little is known about upstream damage response (ELDR) factors sense lead extensive tagging of organelles with signals, such...
Abstract By studying and modelling the behaviour of Dictyostelium discoideum , we aim at deriving mechanisms useful for engineering collective artificial intelligence systems. This paper discusses a selection agent-based models reproducing second-order occurring during migration phase; their corresponding biological illustrations; how used them as an inspiration transposing this into swarms Kilobots. For models, focus on: (1) transition phase from first- to emergent behaviour; (2) slugs’...
Abstract Collective behaviour in nature provides a source of inspiration to engineer artificial collective adaptive systems, due their mechanisms favouring adaptation environmental changes and enabling complex emergent arise from relatively simple individual entities. As part our ongoing research, we study the social amoeba Dictyostelium discoideum derive agent-based models that can then exploit particular swarm robotics. In this paper, present selection aggregation phase D. , corresponding...
ABSTRACT Tuberculosis remains the most pervasive infectious disease and recent emergence of multiple or even fully drug-resistant strains increases risk emphasizes need for more efficient better drug treatments. A key feature mycobacteria pathogenesis is metabolic switch during infection expression virulence genes often adapted to specific conditions. This study aims identify that are involved in establishment maintenance infection. To answer these questions, we have applied Transposon...
Plants have a complex chemo-diversity and represent reservoir of potential new therapeutic agents. Within Swiss research project, six scientific groups from different disciplines are collaborating to investigate collection more than 17’000 unique dried plant extracts. It aims find bioactive molecules their modes action, with for example anti-infective or pro-metabolic activities. One the main challenges this enterprise is management, integration sharing highly heterogeneous data that...
Biotransformation of natural products (NPs) using enzymes represent an alternative to obtain bioactive compounds with original scaffolds and possible new modes action. The concept this approach is start from abundant NPs generate derivatives chemoenzymatic reactions. In context, instead a pure enzyme, we have successfully developed method based on the use enriched pool secreted by phytopathogenic fungus Botrytis cinerea [1]. reaction mixtures are monitored UHPLC-PDA-ELSD-HRMS metabolite...