A5048002837- CRISPR and Genetic Engineering
- Microtubule and mitosis dynamics
- Photosynthetic Processes and Mechanisms
- Photoreceptor and optogenetics research
- Cellular Mechanics and Interactions
- Genomics and Chromatin Dynamics
- Light effects on plants
- Cellular transport and secretion
- Microbial Metabolic Engineering and Bioproduction
- DNA Repair Mechanisms
- Animal Genetics and Reproduction
- Monoclonal and Polyclonal Antibodies Research
- Wnt/β-catenin signaling in development and cancer
- Cancer therapeutics and mechanisms
- Viral Infectious Diseases and Gene Expression in Insects
- Alzheimer's disease research and treatments
- Pluripotent Stem Cells Research
- Diabetes and associated disorders
- Tissue Engineering and Regenerative Medicine
- Skin and Cellular Biology Research
- Glutathione Transferases and Polymorphisms
- N-Heterocyclic Carbenes in Organic and Inorganic Chemistry
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Advanced biosensing and bioanalysis techniques
- Gene expression and cancer classification
Janssen (Switzerland)
2023
ETH Zurich
2018-2022
Board of the Swiss Federal Institutes of Technology
2019
University of Konstanz
2009-2015
Neuronal activity can be modulated by mechanical stimuli. To study this phenomenon quantitatively, we mechanically stimulated rat cortical neurons shear stress and local indentation. Neurons show 2 distinct responses, classified as transient sustained. Transient responses display fast kinetics, similar to spontaneous neuronal activity, whereas sustained last several minutes before returning baseline. Local soma stimulations with micrometer-sized beads evoke at low forces of ∼220 nN pressures...
Wearable smart electronic devices, such as watches, are generally equipped with green-light-emitting diodes, which used for photoplethysmography to monitor a panoply of physical health parameters. Here, we present traceless, green-light-operated, smart-watch-controlled mammalian gene switch (Glow Control), composed an engineered membrane-tethered green-light-sensitive cobalamin-binding domain Thermus thermophilus (TtCBD) CarH protein in combination synthetic cytosolic TtCBD-transactivator...
Turning the motor off: A malachite green based assay leads to identification of BTB-1 (see picture), first small-molecule inhibitor mitotic protein Kif18A. reversibly inhibits ATPase activity recombinant domain Kif18A in vitro picture; red microtubules, blue/black structure =Kif18A) and will be a valuable tool dissect mechanochemical properties
1-Methyl-4-phenyl-tetrahydropyridine (MPTP) is among the most widely used neurotoxins for inducing experimental parkinsonism. MPTP causes parkinsonian symptoms in mice, primates, and humans by killing a subpopulation of dopaminergic neurons. Extrapolations data obtained using MPTP-based parkinsonism models to human disease are common; however, precise mechanism which converted into its active neurotoxic metabolite, 1-methyl-4-phenyl-pyridinium (MPP(+)), has not been fully elucidated. In this...
Emerging digital assessment of biomarkers by linking health-related data obtained from wearable electronic devices and embedded health fitness sensors in smartphones is opening up the possibility creating a continuous remote-monitoring platform for disease management. It considered that built-in flashlight may be utilized to remotely program genetically engineered designer cells on-demand delivery protein-based therapeutics. Here, authors present smartphone-induced insulin release β-cell...
Abstract Cellular therapies remain constrained by the limited availability of sensors for disease markers. Here we present an integrated target-to-receptor pipeline constructing a customizable advanced modular bispecific extracellular receptor (AMBER) that combines our generalized molecule sensor (GEMS) system with high-throughput platform generating designed ankyrin repeat proteins (DARPins). For proof concept, chose human fibrin degradation products (FDPs) as markers high clinical...
The exact biological functions of individual DNA polymerases still await clarification, and therefore appropriate reagents to probe their respective are required. In the present study, we report development a highly potent series human polymerase λ β (pol β) inhibitors based on rhodanine scaffold. Both enzymes involved in repair thus considered as future drug targets. We expanded chemical diversity small-molecule arising from high content screening designed synthesized 30 novel analogues. By...
The mitotic spindle, a highly dynamic structure composed of microtubules, mediates the segregation previously duplicated genome into two nascent daughter cells. Errors in this process contribute to pathology including tumor formation. Key for shape and function spindle are kinesins, molecular motor proteins that convert chemical energy mechanical work. Due their fast mode action, small molecules valuable tools dissect functions kinesins during mitosis. In study, we report identification...
To discover chemical probes to further under-stand the function of individual DNA polymerases, we established a generally applicable high-throughput screening. By applying this technique discovered three novel inhibitor classes human polymerase λ (DNA Pol λ), key enzyme maintain genetic integrity genome. The rhodanines, classified as an excellent drug scaffold, were found be most potent inhibitors for λ. Importantly, they are up 10 times less active against highly similar β. We investigated...
Acetone can be degraded by aerobic and anaerobic microorganisms. Studies with the strictly sulfate-reducing bacterium Desulfococcus biacutus indicate that acetone degradation these bacteria starts an ATP-dependent carbonylation reaction leading to acetoacetaldehyde as first product. The represents second example of a in biochemistry bacteria, but exact mechanism dependence on cofactors are still unclear. Here, we use novel fluorogenic ATP analogue investigate its mechanism. We find thiamine...
Thiazolides are a novel class of anti-infectious agents against intestinal intracellular and extracellular protozoan parasites, bacteria, viruses. While the parent compound nitazoxanide (NTZ; 2-(acetolyloxy)-N-(5-nitro-2-thiazolyl)benzamide) has potent antimicrobial activity, bromo-thiazolide RM4819 (N-(5-bromothiazol-2-yl)-2-hydroxy-3-methylbenzamide) shows only reduced activity. Interestingly, both molecules able to induce cell death in colon carcinoma lines, indicating that molecular...
In humans, cellular mechanoperception serves as the basis of touch sensation and proprioception, contributes to proper programming cell fate during embryonic development, plays a pivotal role in development mechanosensitive tissues. Molecular mechanoreceptors can respond their environment by mediating transient adjustments ion homeostasis, which subsequently trigger calcium-dependent alteration gene expression via specific signaling pathways such nuclear factor activated T-cells pathway....
The reaction of the bis(amino)allenylidene complex [(CO)5W═C═C═C(NMe2)2] with diethyldiazomethane yields two products, a cyclic carbene (2) by 1,2-addition Et2C−N2 to Cα−Cβ bond allenylidene ligand and η1-butatriene [(CO)5W{C[C(NMe2)2]═C═CEt2}] (3). Complex 2 slowly eliminates N2 rearranges into 3. In contrast, only complexes, [(CO)5M{C[C(NMe2)XR]═C═C(R′)2}], are isolated from diazoalkanes (R′)2C−N2 (R′ = Me, Et, nPr) alkoxy(amino)allenylidene complexes [(CO)5M═C═C═C(NMe2)OR] (M Cr, W; R...
Motor abgewürgt: Mithilfe eines auf Malachitgrün beruhenden Assays gelang die Identifizierung von BTB-1 (siehe Bild), dem ersten niedermolekularen Inhibitor Kif18A. hemmt ATPase-Aktivität der rekombinanten Motordomäne Kif18A in vitro reversibel (rot=Mikrotubulus, blau-schwarze Struktur=Kif18A) und wird ein nützliches Hilfsmittel für Analyse mechanochemischen Eigenschaften sein. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents...
Abstract In this study, we designed and built a gene switch that employs metabolically inert l ‐glucose to regulate transgene expression in mammalian cells via d ‐idonate‐mediated control of the bacterial regulator LgnR. To end, engineered metabolic cascade produce inducer molecule ‐idonate from its precursor by ectopically expressing Paracoccus species 43P‐derived catabolic enzymes LgdA, LgnH , LgnI . obtain ON‐ OFF‐switches, fused LgnR human transcriptional silencer domain Krüppel...
Current molecular cloning strategies generally lack inter-compatibility, are not strictly modular, or applicable to engineer multi-gene expression vectors for transient and stable integration. A standardized platform would advance research, example, by promoting exchange of between groups. Here, we present a versatile plasmid architecture mammalian synthetic biology, which designate VAMSyB, consisting three-tier vector family. Tier-1 is designed easy engineering fusion constructs, as well...
Anticoagulants play a critical role in the prevention and treatment of thrombotic-driven cardiovascular diseases. Factor XIa (FXIa) inhibitors have potential to improve benefit/risk profile existing anticoagulants through safer bleeding variety conditions where patients are predisposed high risk thrombotic or events. To support clinical development program milvexian (BMS-986177/JNJ-70033093), FXIa inhibitor that recently completed phase II trials, we improved discovery route deliver suitable...
We designed and engineered a dye production cassette encoding heterologous pathway, including human tyrosine hydroxylase Amanita muscaria 4,5-DOPA dioxygenase, for the biosynthesis of betaxanthin family plant fungal pigments in mammalian cells. The system does not impair cell viability, can be used as non-protein reporter to directly visualize dynamics gene expression by profiling absorbance or fluorescence supernatant cultures, well labeling individual Pigment also multiplexed with proteins...
Starting from available ribose-building blocks, the 4′-C-methyl-, 4′-C-ethyl-and new 4′-Cpropyl-substituted deoxyuridines were synthesized.Afterwards we converted 4′-C-alkylated-2′deoxyuridines into corresponding 4′-C-alkylated-5-iodo-2′-deoxyuridines 3a-c and those in turn 4′-C-alkylated-5-iodo-2′-deoxycytidines 4a-c.
Abstract Mechanical cues are involved in many biological processes, including embryonic development and patterning. For example, external mechanical forces (shear stress), lateral cell–cell interactions, properties (stiffness composition) of the extracellular matrix thought to modulate Wnt signaling, which is a highly conserved pathway regulating stem cell renewal, proliferation, differentiation. In this work, we employed customized higher‐throughput shear stress induction device for...