A5052676583- Enzyme Structure and Function
- Microbial Community Ecology and Physiology
- Seismology and Earthquake Studies
- Bacterial Genetics and Biotechnology
- Methane Hydrates and Related Phenomena
- Enzyme Production and Characterization
- Glycosylation and Glycoproteins Research
- Antibiotic Resistance in Bacteria
- Vibrio bacteria research studies
- Carbohydrate Chemistry and Synthesis
- Bacillus and Francisella bacterial research
- Galectins and Cancer Biology
- Genomics and Phylogenetic Studies
- Bacteriophages and microbial interactions
- Escherichia coli research studies
- Protein Structure and Dynamics
- CAR-T cell therapy research
- Yersinia bacterium, plague, ectoparasites research
- Marine and coastal plant biology
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Pharmacogenetics and Drug Metabolism
- Lysosomal Storage Disorders Research
- Advanced Proteomics Techniques and Applications
- Protist diversity and phylogeny
University of British Columbia
2020-2024
AbCellera (Canada)
2024
University of Victoria
2010-2022
University of Bremen
2017-2022
Max Planck Institute for Marine Microbiology
2017-2022
Abstract Polysaccharide degradation by heterotrophic microbes is a key process within Earth’s carbon cycle. Here, we use environmental proteomics and metagenomics in combination with cultivation experiments biochemical characterizations to investigate the molecular details of situ polysaccharide mechanisms during microalgal blooms. For this, laminarin as model polysaccharide. Laminarin ubiquitous marine storage polymer microalgae particularly abundant phytoplankton In this study, show that...
The Francisella pathogenicity island (FPI) encodes proteins thought to compose a type VI secretion system (T6SS) that is required for the intracellular growth of novicida. In this work we used deletion mutagenesis and genetic complementation determine F. novicida was dependent on 14 18 genes in FPI. products iglABCD operon were localized by biochemical fractionation novicida, tularensis LVS. Sucrose gradient separation water-insoluble material showed FPI-encoded IglA, IglB IglC found...
Marine microscopic algae carry out about half of the global carbon dioxide fixation into organic matter. They provide substrates for marine microbes such as members Bacteroidetes that degrade algal polysaccharides using carbohydrate-active enzymes (CAZymes). In genomes CAZyme encoding genes are mostly grouped in distinct regions termed polysaccharide utilization loci (PULs). While some studies have shown involvement PULs degradation polysaccharides, specific most part still unknown. We...
Abstract The polysaccharide β-mannan, which is common in terrestrial plants but unknown microalgae, was recently detected during diatom blooms. We identified a β-mannan utilization locus (PUL) the genome of marine flavobacterium Muricauda sp. MAR_2010_75. Proteomics showed induced translation 22 proteins encoded within PUL. Biochemical and structural analyses deduced enzymatic cascade for utilization. A conserved GH26 β-mannanase with endo-activity depolymerized β-mannan. Consistent...
Staphylococcus aureus, an ESKAPE pathogen, is a major clinical concern due to its pathogenicity and manifold antimicrobial resistance mechanisms. The commonly used β-lactam antibiotics target bacterial penicillin-binding proteins (PBPs) inhibit crosslinking of peptidoglycan strands that comprise the cell wall mesh, initiating cascade effects leading death. S. aureus PBP1 involved in synthesis during division presence essential for survival both antibiotic susceptible resistant strains. Here,...
Marine bacteria catabolize carbohydrate polymers of algae, which synthesize these structurally diverse molecules in ocean surface waters. Although algal glycans are an abundant carbon and energy source the ocean, molecular details that enable specific recognition between bacterial degraders remain largely unknown. Here we characterized a protein, GMS usD from planktonic Bacteroidetes‐Gramella sp. MAR _2010_102 thrives during blooms. Our biochemical structural analyses show binds glucose...
Abstract Accessing peptides from intracellular tumor antigens displayed on MHC class I (pMHC) can expand the T-cell engager (TCE) target pool for solid applications. A challenge limiting TCE development pMHC targets is identification of rare, high-affinity, and high-specificity pMHC-binders. In this work, we describe TCEs in a 1 × format with potent tumor-cell killing activity high specificity MAGE-A4, antigen expressed multiple cancer types. We identified functional MAGE-A4 x CD3 affinity...
The type VI secretion system of Pseudomonas aeruginosa has been shown to be responsible for the translocation bacteriolytic effectors into competing bacteria. A mechanistic understanding this widely distributed is developing and structural studies its components are ongoing. Two representative structures one highly conserved component, TssJ, from Escherichia coli Serratia marcescens have published. Here, X-ray crystal structure TssJ1 P. presented at 1.4 Å resolution. overall among three...
Degradation of carbohydrates by bacteria represents a key step in energy metabolism that can be inhibited methylated sugars. Removal methyl groups, which is critical for further processing, poses biocatalytic challenge because enzymes need to overcome high barrier. Our structural and computational analysis revealed how member the cytochrome P450 family evolved oxidize carbohydrate ligand. Using biology, we ascertained molecular determinants substrate specificity highly specialized active...
Peptidoglycan (PG) is an essential component of the bacterial cell wall and assembled from a lipid II precursor by glycosyltransferase transpeptidase reactions catalyzed in particular bifunctional class A penicillin-binding proteins (aPBPs). In major clinical pathogen Pseudomonas aeruginosa, PBP1B anchored within cytoplasmic membrane but regulated bespoke outer membrane-localized lipoprotein known as LpoP. Here, we report structure LpoP, showing extended N-terminal, flexible tether followed...
Tularaemia is an uncommon but potentially dangerous zoonotic disease caused by the bacterium Francisella tularensis. As few as ten bacterial cells are sufficient to cause in a healthy human, making this one of most infectious agents known. The virulence organism dependent upon genetic locus known pathogenicity island (FPI), which encodes components secretion system that related type VI system. Here, cloning, expression, purification and preliminary X-ray diffraction statistics FPI-encoded...
The recently identified marine bacterium Pseudoalteromonas fuliginea sp. PS47 possesses a polysaccharide-utilization locus dedicated to agarose degradation. In particular, it contains gene (locus tag EU509_06755) encoding β-agarase that belongs glycoside hydrolase family 50 (GH50), Pf GH50B. 2.0 Å resolution X-ray crystal structure of GH50B reveals rare complex multidomain fold was found in two the three previously determined GH50 structures. comprises an N-terminal domain with...
Current vaccine efforts to combat SARS-CoV-2 are focused on the whole spike protein administered as mRNA, viral vector, or subunit. However, receptor-binding domain (RBD) is immunodominant portion of protein, accounting for 90% serum neutralizing activity. In this study, we constructed several versions RBD and together with aluminum hydroxide DDA (dimethyldioctadecylammonium bromide)/TDB (d-(+)-trehalose 6,6'-dibehenate) adjuvant evaluated immunogenicity in mice. We generated human...
Abstract Algae catalyze half of the global solar powered reduction carbon dioxide to organic molecules. While this synthesis shapes genomes heterotrophic microbiota globally, many corresponding structures remain elusive. We show that diatoms release a mannan polyelectrolyte selecting for bacteria with specifically adapted enzymatic cascade. NMR spectroscopy, chromatography, automated glycan assembly and dissection resolved structure C6 sulfated α-1,3-mannan exceptional simplicity...
Abstract Algal polysaccharides of diverse structures are one the most abundant carbon resources for heterotrophic, marine bacteria with coevolved digestive enzymes. A putative sulfo‐mannan polysaccharide utilization locus, which is conserved in flavobacteria, contains an unusual GH99‐like protein that lacks catalytic residues glycoside hydrolase family 99. Using X‐ray crystallography, we structurally characterized this from flavobacterium Ochrovirga pacifica to help elucidate its molecular...