Tristan W. Owens
A5010485022- Bacterial Genetics and Biotechnology
- RNA and protein synthesis mechanisms
- interferon and immune responses
- Antibiotic Resistance in Bacteria
- SARS-CoV-2 and COVID-19 Research
- Drug Transport and Resistance Mechanisms
- Cell Image Analysis Techniques
- Enzyme Structure and Function
- Machine Learning in Bioinformatics
- RNA modifications and cancer
- Computational Drug Discovery Methods
- Antimicrobial Resistance in Staphylococcus
- Protein Structure and Dynamics
- Bacteriophages and microbial interactions
- X-ray Diffraction in Crystallography
- Escherichia coli research studies
- Pediatric Hepatobiliary Diseases and Treatments
- Biochemical and Structural Characterization
- Amino Acid Enzymes and Metabolism
- Neurobiology and Insect Physiology Research
- Ion Channels and Receptors
- Microbial Natural Products and Biosynthesis
- Antibiotics Pharmacokinetics and Efficacy
- Crystallization and Solubility Studies
- Cancer Genomics and Diagnostics
Harvard University
2016-2021
University of California, San Francisco
2020-2021
Molecular Biology Consortium
2020-2021
Quantitative BioSciences
2020
Cornell University
2011
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 closely related more lethal but less transmissible coronaviruses SARS-CoV-1 Middle East (MERS-CoV). Here, we have carried out comparative viral-human protein-protein interaction viral protein localization analyses for all three viruses. Subsequent functional genetic screening identified host factors that functionally impinge on...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) macrodomain within the nonstructural protein 3 counteracts host-mediated antiviral adenosine diphosphate-ribosylation signaling. This enzyme is a promising target because catalytic mutations render viruses nonpathogenic. Here, we report massive crystallographic screening and computational docking effort, identifying new chemical matter primarily targeting active site of macrodomain. Crystallographic 2533 diverse fragments...
Abstract The SARS-CoV-2 protein Nsp2 has been implicated in a wide range of viral processes, but its exact functions, and the structural basis those remain unknown. Here, we report an atomic model for full-length obtained by combining cryo-electron microscopy with deep learning-based structure prediction from AlphaFold2. resulting reveals highly-conserved zinc ion-binding site, suggesting role RNA binding. Mapping emerging mutations variants on shows potential host-Nsp2 interaction regions....
We have previously shown that PIP5KIβ and PIP5KIγ generate functionally distinct pools of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] important for antigen-stimulated Ca2+ entry in mast cells. In the present study, we find association endoplasmic reticulum (ER) sensor, STIM1, store-operated channel, Orai1, stimulated by thapsigargin-mediated ER store depletion, is enhanced overexpression inhibited PIP5KIγ. These different PIP5KI isoforms cause differential enhancement PtdIns(4,5)P2...
Novobiocin is an orally active antibiotic that inhibits DNA gyrase by binding the ATP-binding site in ATPase subunit. Although effective against Gram-positive pathogens, novobiocin has limited activity Gram-negative organisms due to presence of lipopolysaccharide-containing outer membrane, which acts as a permeability barrier. Using novobiocin-sensitive Escherichia coli strain with leaky we identified mutant increased resistance novobiocin. Unexpectedly, mutation increases was not found...
Gram-negative bacteria are challenging to kill with antibiotics due their impenetrable outer membrane containing lipopolysaccharide (LPS). The polymyxins, including colistin, the drugs of last resort for treating infections. These bind LPS and disrupt membrane; however, toxicity limits usefulness. Polymyxin has been shown synergize many novobiocin, which inhibits DNA gyrase, by facilitating transport these across membrane. Recently, we have that novobiocin not only gyrase but also binds...
ABSTRACT The surface of most Gram-negative bacteria is covered with lipopolysaccharide (LPS), creating a permeability barrier against toxic molecules, including many antimicrobials. To assemble LPS on their surface, must extract newly synthesized from the inner membrane, transport it across aqueous periplasm, and translocate outer membrane. LptA to -G proteins into transenvelope complex that transports membrane cell surface. Lpt system powers by using poorly characterized ATP-binding...
The Gram-positive bacterial cell wall is a large supramolecular structure and its assembly requires coordination of complex biosynthetic pathways. In the step that merges two major pathways in Staphylococcus aureus assembly, conserved protein ligases attach teichoic acids to peptidoglycan, but order events longstanding question. Here, we use chemical approach define which possible peptidoglycan intermediates are substrates for wall-teichoic acid ligases, thereby establishing assembly. We...
Antibiotic-resistant strains of Staphylococcus aureus pose a major threat to human health and there is an ongoing need for new antibiotics treat resistant infections. In high throughput screen (HTS) 230 000 small molecules designed identify bioactive wall teichoic acid (WTA) inhibitors, we identified one hit, which was expanded through chemical synthesis into panel potent compounds. We showed that these compounds target TarG, the transmembrane component two-component ATP-binding cassette...
ATP-binding cassette (ABC) transporters constitute a large family of proteins present in all domains life. They are powered by dynamic ATPases that harness energy from binding and hydrolyzing ATP through cycle involves the closing reopening their two domains. The LptB2FGC exporter is an essential ABC transporter assembles lipopolysaccharides (LPS) on surface Gram-negative bacteria to form permeability barrier against many antibiotics. extracts newly synthesized LPS molecules inner membrane...
ABSTRACT The SARS-CoV-2 macrodomain (Mac1) within the non-structural protein 3 (Nsp3) counteracts host-mediated antiviral ADP-ribosylation signalling. This enzyme is a promising target because catalytic mutations render viruses non-pathogenic. Here, we report massive crystallographic screening and computational docking effort, identifying new chemical matter primarily targeting active site of macrodomain. Crystallographic diverse fragment libraries resulted in 214 unique macrodomain-binding...
The SARS-CoV-2 protein Nsp2 has been implicated in a wide range of viral processes, but its exact functions, and the structural basis those remain unknown. Here, we report an atomic model for full-length obtained by combining cryo-electron microscopy with deep learning-based structure prediction from AlphaFold2. resulting reveals highly-conserved zinc ion-binding site, suggesting role RNA binding. Mapping emerging mutations variants on shows potential host-Nsp2 interaction regions. Using...
Antibiotics to treat drug-resistant Gram-negative infections are urgently needed but challenging discover. Using a cell-based screen, we identified simple secondary amine that inhibited the growth of wild-type Escherichia coli and Acinetobacter baumannii not Gram-positive organism Bacillus subtilis. Resistance mutations in E. A. mapped exclusively aminoacyl-tRNA synthetase PheRS. We confirmed biochemically compound PheRS from these organisms showed it did inhibit B. subtilis or humans. To...