A5025068841- RNA and protein synthesis mechanisms
- Bacteriophages and microbial interactions
- Receptor Mechanisms and Signaling
- Advanced Electron Microscopy Techniques and Applications
- Enzyme Structure and Function
- Vibrio bacteria research studies
- Bacterial Genetics and Biotechnology
- Neuropeptides and Animal Physiology
- Escherichia coli research studies
- Electron and X-Ray Spectroscopy Techniques
- Protein Kinase Regulation and GTPase Signaling
- Microbial Natural Products and Biosynthesis
- Adenosine and Purinergic Signaling
- Monoclonal and Polyclonal Antibodies Research
- Diabetes Treatment and Management
- Viral Infections and Immunology Research
- Growth Hormone and Insulin-like Growth Factors
- Heat shock proteins research
- RNA Research and Splicing
- Organic Electronics and Photovoltaics
- Advanced Materials Characterization Techniques
- Peptidase Inhibition and Analysis
- RNA modifications and cancer
- Microtubule and mitosis dynamics
- Genomics and Phylogenetic Studies
Australian Regenerative Medicine Institute
2019-2025
Monash University
2018-2025
Discovery Institute
2024
University Medical Center Utrecht
2023
Sri Siddhartha Academy of Higher Education
2021
Sri Siddhartha Medical College
2021
University of Auckland
2013-2019
ARC Centre of Excellence in Advanced Molecular Imaging
2018
Massey University
2009-2011
Significance Neutralizing antibodies are important for immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and as therapeutics the prevention treatment of COVID-19. We identified high-affinity nanobodies SARS-CoV-2 receptor-binding domain found that nanobody cocktails consisting two noncompeting were able to block ACE2 engagement with RBD variants present in human populations potently neutralize both wild-type N501Y D614G variant at low concentrations. Prophylactic...
Abstract Diverse aerobic bacteria use atmospheric H 2 as an energy source for growth and survival 1 . This globally significant process regulates the composition of atmosphere, enhances soil biodiversity drives primary production in extreme environments 2,3 Atmospheric oxidation is attributed to uncharacterized members [NiFe] hydrogenase superfamily 4,5 However, it remains unresolved how these enzymes overcome extraordinary catalytic challenge oxidizing picomolar levels amid ambient poison O...
The compaction of chromatin is a prevalent paradigm in gene repression. Chromatin commonly thought to repress transcription by restricting accessibility. However, the spatial organization and dynamics compacted gene-repressing factors are unknown. Here, using cryo-electron tomography, we solved three-dimensional structure condensed polycomb repressive complex 1 (PRC1) with CBX8. PRC1-condensed porous stabilized through multivalent dynamic interactions PRC1 chromatin. Mechanistically,...
Abstract Macrophage-expressed gene 1 (MPEG1/Perforin-2) is a perforin-like protein that functions within the phagolysosome to damage engulfed microbes. MPEG1 thought form pores in target membranes, however, its mode of action remains unknown. We use cryo-Electron Microscopy (cryo-EM) determine 2.4 Å structure hexadecameric assembly displays expected features soluble prepore complex. further discover prepore-like assemblies can be induced perforate membranes through acidification, such as...
G protein–coupled receptors (GPCRs) are critical regulators of cellular function acting via heterotrimeric proteins as their primary transducers with individual GPCRs capable pleiotropic coupling to multiple proteins. Structural features governing protein selectivity and promiscuity currently unclear. Here, we used cryo-electron microscopy (cryo-EM) determine structures the cholecystokinin (CCK) type 1 receptor (CCK1R) bound CCK peptide agonist, CCK-8 2 distinct transducer proteins, its Gq,...
The glucagon-like peptide-1 receptor (GLP-1R) has broad physiological roles and is a validated target for treatment of metabolic disorders. Despite recent advances in GLP-1R structure elucidation, detailed mechanistic understanding how different peptides generate profound differences G protein-mediated signalling still lacking. Here we combine cryo-electron microscopy, molecular dynamics simulations, mutagenesis pharmacological assays, to interrogate the mechanism consequences binding four...
Lysosomes have crucial roles in regulating eukaryotic metabolism and cell growth by acting as signalling platforms to sense respond changes nutrient energy availability
The structure of an infectious immature flavivirus redefines viral architecture and maturation.
Potent neutralizing monoclonal antibodies are one of the few agents currently available to treat COVID-19. SARS-CoV-2 variants concern (VOCs) that carry multiple mutations in viral spike protein can exhibit neutralization resistance, potentially affecting effectiveness some antibody-based therapeutics. Here, generation a diverse panel 91 human, provides an in-depth structural and phenotypic definition receptor binding domain (RBD) antigenic sites on spike. These RBD ameliorate infection mice...
Abstract The epidemic emergence of relatively rare and geographically isolated flaviviruses adds to the ongoing disease burden viruses such as dengue. Structural analysis is key understand combat these pathogens. Here, we present a chimeric platform based on an insect-specific flavivirus for safe rapid structural pathogenic viruses. We use this approach resolve architecture two neurotropic structure dengue virus at 2.5 Å, highest resolution enveloped virion. These reconstructions allow...
Monomers of the insulin receptor and type 1 insulin-like growth factor (IGF-1R) can combine stochastically to form heterodimeric hybrid receptors. These receptors display ligand binding signaling properties that differ from those homodimeric Here, we describe cryoelectron microscopy structure such a in complex with I (IGF-I). The (ca. 3.7 Å resolution) displays single IGF-I ligand, bound similar fashion seen for IGFs IGF-1R. engages first leucine-rich-repeat domain cysteine-rich region...
The insulin/IGF superfamily is conserved across vertebrates and invertebrates. Our team has identified five viruses containing genes encoding viral insulin/IGF-1 like peptides (VILPs) closely resembling human insulin IGF-1. This study aims to characterize the impact of Mandarin fish ranavirus (MFRV) Lymphocystis disease virus-Sa (LCDV-Sa) VILPs on system for first time. We chemically synthesized single chain (sc, IGF-1 like) double (dc, forms MFRV LCDV-Sa VILPs. Using cell lines...
The class A orphan G protein-coupled receptor (GPCR), GPR3, has been implicated in a variety of conditions, including Alzheimer's and premature ovarian failure. GPR3 constitutively couples with Gαs, resulting the production cAMP cells. While tool compounds several putative endogenous ligands have emerged for receptor, its ligand, if it exists, remains mystery. As novel potential drug targets, structures GPCRs increasing interest, revealing distinct modes activation, autoactivation, presence...
Bacteriocins are bacterial peptides with specific activity against competing species. They hold great potential as natural preservatives and for their probiotic effects. We show here nuclear magnetic resonance-based evidence that glycocin F, a 43-amino acid bacteriocin from Lactobacillus plantarum, contains two β-linked N-acetylglucosamine moieties, attached via side chain linkages to serine oxygen, cysteine sulfur. The latter linkage is novel has helped establish new type of...
Abstract Complement component 9 (C9) functions as the pore-forming of Membrane Attack Complex (MAC). During MAC assembly, multiple copies C9 are sequentially recruited to membrane associated C5b8 form a pore. Here we determined 2.2 Å crystal structure monomeric murine and 3.9 resolution cryo EM in polymeric assembly. Comparison with other proteins reveals that first transmembrane region (TMH1) is uniquely positioned inhibit its self-assembly absence C5b8. We further show following...
Human type 1 insulin-like growth factor receptor (IGF-1R) signals chiefly in response to the binding of I. Relatively little is known about role II signaling via IGF-1R, despite affinity for IGF-1R being within an order magnitude that Here, we describe cryoelectron microscopy structure bound a leucine-zipper-stabilized ectodomain, determined two conformations maximum average resolution 3.2 Å. The differ relative separation their respective points membrane entry, and comparison with I reveals...
Abstract Flagellotropic bacteriophages engage flagella to reach the bacterial surface as an effective means increase capture radius for predation. Structural details of these viruses are great interest given substantial drag forces and torques they face when moving down spinning flagellum. We show that main capsid auxiliary proteins form two nested chainmails ensure integrity bacteriophage head. Core stabilising structures conserved in herpesviruses suggesting their ancestral origin. The...
We developed a series of highly crystalline double-cable conjugated polymers for application in single-component organic solar cells (SCOSCs). These contain backbones as electron donor and pendant perylene bisimide units (PBIs) acceptor. PBIs are connected to the backbone via alkyl varying from hexyl (C6 H12 ) eicosyl (C20 H40 flexible linkers. For with short linkers, tend stack head-to-head fashion, resulting large d-spacings (e.g. 64 Å polymer P12 C12 H24 linker) along lamellar stacking...