A5082015812- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- RNA and protein synthesis mechanisms
- Photosynthetic Processes and Mechanisms
- Advanced Electron Microscopy Techniques and Applications
- Genetic Neurodegenerative Diseases
- RNA modifications and cancer
- Folate and B Vitamins Research
- Lipid Membrane Structure and Behavior
- Mitochondrial Function and Pathology
- Antibiotic Resistance in Bacteria
- Cancer Research and Treatments
- Genomics and Phylogenetic Studies
- Cell Image Analysis Techniques
- Muscle Physiology and Disorders
- DNA and Nucleic Acid Chemistry
- Biochemical and Molecular Research
- Microfluidic and Bio-sensing Technologies
- Tardigrade Biology and Ecology
- Porphyrin Metabolism and Disorders
- Antimicrobial Resistance in Staphylococcus
- Amino Acid Enzymes and Metabolism
- Drug Transport and Resistance Mechanisms
- Insect and Arachnid Ecology and Behavior
- Complement system in diseases
National Cancer Institute
2021-2025
Center for Cancer Research
2020-2025
National Institutes of Health
2023-2024
Joint Center for Structural Genomics
2023-2024
University of Oxford
2016-2023
Government of the United States of America
2023
Sir Robert McAlpine (United Kingdom)
2020-2021
McGill University
2012-2015
Cysteine plays an essential role in cellular redox homoeostasis as a key constituent of the tripeptide glutathione (GSH). A rate limiting step GSH synthesis is availability cysteine. However, circulating cysteine exists blood oxidised di-peptide cystine, requiring specialised transport systems for its import into cell. System xc
Structure of PepT2 reveals binding model for peptide recognition and enables a more rationalized approach to prodrug design.
Abstract Lipid droplets (LDs) are universal lipid storage organelles with a core of neutral lipids, such as triacylglycerols, surrounded by phospholipid monolayer. This unique architecture is generated during LD biogenesis at endoplasmic reticulum (ER) sites marked Seipin, conserved membrane protein mutated in lipodystrophy. Here structural, biochemical and molecular dynamics simulation approaches reveal the mechanism formation yeast Seipin Sei1 its partner Ldb16. We show that luminal domain...
Abstract Secretion systems are protein export machines that enable bacteria to exploit their environment through the release of effectors. The Type 9 System (T9SS) is responsible for across outer membrane (OM) phylum Bacteroidota. Here we trap T9SS Flavobacterium johnsoniae in process substrate transport by disrupting motor complex. Cryo-EM analysis purified substrate-bound translocons reveals an extended translocon structure which previously described core augmented a periplasmic...
Protein secretion through type-three systems (T3SS) is critical for motility and virulence of many bacteria. Proteins are transported an export gate containing three proteins (FliPQR in flagella, SctRST systems). A fourth essential T3SS protein (FlhB/SctU) functions to "switch" substrate specificity once the growing hook/needle reach their determined length. Here, we present cryo-electron microscopy structure switch from a Vibrio flagellar system at 3.2 Å resolution. The reveals that...
Tuberculosis (TB) is the leading cause of death from a single infectious agent and in 2019 an estimated 10 million people worldwide contracted disease. Although treatments for TB exist, continual emergence drug-resistant variants necessitates urgent development novel antituberculars. An important new target lipid transporter MmpL3, which required construction unique cell envelope that shields Mycobacterium tuberculosis (Mtb) immune system. However, structural understanding mutations Mtb...
Abstract Huntington’s disease results from expansion of a glutamine-coding CAG tract in the huntingtin (HTT) gene, producing an aberrantly functioning form HTT. Both wildtype and disease-state HTT hetero-dimer with HAP40 unknown functional relevance. We demonstrate vivo cell models that cellular abundance are coupled. Integrating data 2.6 Å cryo-electron microscopy structure, cross-linking mass spectrometry, small-angle X-ray scattering, modeling, we provide near-atomic-level view HTT, its...
Although predicted on the basis of sequence conservation, work presented here formally demonstrates that all classes type III secretion systems, flagellar or virulence, share same architecture at level core structures. This absolute conservation unusual extramembrane structure export gate complex now allows to move focusing both mechanistic studies but also fundamental how such a is assembled.
We here introduce the third major release of SIMPLE (Single-particle IMage Processing Linux Engine) open-source software package for analysis cryogenic transmission electron microscopy (cryo-EM) movies single-particles (Single-Particle Analysis, SPA). Development 3.0 has been focused on real-time data processing using minimal CPU computing resources to allow easy and cost-efficient scaling as rates escalate. Our stream SPA tool implements steps anisotropic motion correction CTF estimation,...
is an opportunistic human pathogen associated with severe infections and antimicrobial resistance.
Urease is a nickel (Ni) enzyme that essential for the colonization of Helicobacter pylori in human stomach. To solve problem delivering toxic Ni ion to active site without diffusing into cytoplasm, cells have evolved metal carrier proteins, or metallochaperones, deliver ions specific protein complexes. delivery requires urease form an activation complex with accessory proteins UreFD and UreG. Here, we determined cryo–electron microscopy structures H. UreFD/urease Klebsiella pneumoniae...
In Gram negative bacteria the outer membrane (OM) is first line of defence against antimicrobial agents and immunological attacks. A key part OM biogenesis insertion proteins (OMPs) by beta barrel assembly machinery (BAM). Here we report cryo-electron microscopy (cryoEM) structure a BAM complex isolated from Flavobacterium johnsoniae, member phylum Bacteroidota that includes human commensals major anaerobic pathogens. This radically different canonical Escherichia coli system an extensive...