A5083144855- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Advanced Biosensing Techniques and Applications
- Protease and Inhibitor Mechanisms
- Complement system in diseases
- Advanced biosensing and bioanalysis techniques
- Biosensors and Analytical Detection
- Autoimmune and Inflammatory Disorders Research
- Acute Lymphoblastic Leukemia research
- Advanced Proteomics Techniques and Applications
- T-cell and B-cell Immunology
- Protein Structure and Dynamics
- Viral Infections and Immunology Research
- Cell Adhesion Molecules Research
- Nanofabrication and Lithography Techniques
- Cardiomyopathy and Myosin Studies
- Inflammasome and immune disorders
- Streptococcal Infections and Treatments
- Immune Cell Function and Interaction
- Protein purification and stability
- Gastrointestinal disorders and treatments
- Blood Coagulation and Thrombosis Mechanisms
- ATP Synthase and ATPases Research
- Phytoplasmas and Hemiptera pathogens
- Blood groups and transfusion
Monash University
2013-2023
Australian Regenerative Medicine Institute
2016-2023
Translational Research Institute
2020
The University of Queensland
2020
Mater Research
2020
Australian Research Council
2017-2020
Immunocore (United Kingdom)
2020
ARC Centre of Excellence in Advanced Molecular Imaging
2015-2019
Dublin City University
2009-2016
University of Strathclyde
2015
Abstract The membrane attack complex (MAC)/perforin-like protein complement component 9 (C9) is the major of MAC, a multi-protein that forms pores in target pathogens. In contrast to homologous proteins such as perforin and cholesterol-dependent cytolysins (CDCs), all which require for oligomerisation, C9 assembles directly onto nascent MAC from solution. However, molecular mechanism assembly remains be understood. Here we present 8 Å cryo-EM structure soluble form poly-C9 MAC. These data...
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...
Tumor-associated peptide–human leukocyte antigen complexes (pHLAs) represent the largest pool of cell surface–expressed cancer-specific epitopes, making them attractive targets for cancer therapies. Soluble bispecific molecules that incorporate an anti-CD3 effector function are being developed to redirect T cells against these using 2 different approaches. The first achieves pHLA recognition via affinity-enhanced versions natural TCRs (e.g., immune-mobilizing monoclonal receptors [ImmTAC]...
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...
Dysregulation of the inflammatory response underlies numerous diseases. Although most interleukin-1 family cytokines are proinflammatory, human interleukin-37 (IL-37) is a powerful, broad-spectrum inhibitor inflammation and immunity. We determined crystal structure IL-37 to establish anti-inflammatory mechanism this key cytokine in view developing IL-37-based therapies. found that two β-trefoil fold molecules form head-to-head dimer stable solution. variants mutated convert into an obligate...
Key Points TXA is an active-site inhibitor of uPA. attenuates MDA-MB-231 BAG cell migration and inhibits endogenous uPA activity.
The stepwise fabrication of the sensor is highlighted, scFv immobilization, binding pentameric CRP followed by metal labeled fragments.
Abstract The muscular dystrophies encompass a broad range of pathologies with varied clinical outcomes. In the case patients carrying defects in fukutin-related protein (FKRP), these diverse arise from mutations within same gene. This is surprising as FKRP glycosyltransferase, whose only identified function to transfer ribitol-5-phosphate α-dystroglycan (α-DG). Although this modification critical for extracellular matrix attachment, α-DG’s glycosylation status relates poorly disease...
BACKGROUND Acute porphyrias arise from genetic defects in heme synthesis. Significant increases urine porphobilinogen (PBG) levels are diagnostic, enabling further testing and the commencement of targeted therapies. We report a rare case an elderly woman with delayed diagnosis acute variegate porphyria (VP) neurovisceral crisis, anuria, multiorgan failure precipitated by methicillin-sensitive Staphylococcus aureus (MSSA) sepsis. Diagnostic therapeutic difficulties confirming VP crisis anuric...
The zymogen protease plasminogen and its active form plasmin perform key roles in blood clot dissolution, tissue remodeling, cell migration, bacterial pathogenesis. Dysregulation of the plasminogen/plasmin system results life-threatening hemorrhagic disorders or thrombotic vascular occlusion. Accordingly, inhibitors this are clinically important. Currently, tranexamic acid (TXA), a molecule that prevents activation through blocking recruitment to target substrates, is most widely used...
The favorable biophysical attributes of non-antibody scaffolds make them attractive alternatives to monoclonal antibodies. However, due the well-known stability-function trade-off, these gains tend be marginal after functional selection. A notable example is fibronectin Type III (FN3) domain, FNfn10, which has been previously evolved bind lysozyme with 1 pM affinity (FNfn10-α-lys), but suffers from poor thermodynamic and kinetic stability. To explore this compromise further, we grafted...
CUB-domain containing protein 1 (CDCP1) is a cancer associated cell surface that amplifies pro-tumorigenic signalling by other receptors including EGFR and HER2.Its potential as target supported studies showing anti-CDCP1 antibodies inhibit migration survival in vitro, tumor growth metastasis vivo.Here we characterize two antibodies, focusing on immuno-conjugates of one these tool to detect ovarian cancer.Methods: A panel lines was examined for expression CDCP1 loss induced 10D7 41-2 using...
Recent exploitation of the avian immune system has highlighted its suitability for generation high-quality, high-affinity antibodies to a wide range antigens number therapeutic and biotechnological applications. The glycosylation profile potential immunoglobulin therapeutics is species specific heavily influenced by cell-line/culture conditions used production. Hence, knowledge carbohydrate moieties present on immunoglobulins essential as certain glycan structures can adversely impact their...
In vitro diagnostic (IVD) platforms provide rapid and accurate determination of disease status. The clinical performance antibody-based is paramount as the information provided often informs medical intervention taken and, ultimately, patient's outcome. Breaking down such an immuno-IVD device into its component elements, biorecognition entity key to analytical specificity test. Furthermore, tailored optimisation antibody necessary impart desired biophysical properties for specific...
Abstract Conjugation is fundamental for the acquisition of new genetic traits and development antibiotic resistance in pathogenic organisms. Here, we show that a hypothetical Clostridium perfringens protein, TcpK, which encoded by tetracycline plasmid pCW3, essential efficient conjugative DNA transfer. Our studies reveal TcpK member winged helix-turn-helix (wHTH) transcription factor superfamily it forms dimer solution. Furthermore, specifically binds to nine-nucleotide sequence present as...
The diagnosis and treatment of prostate cancer (PCa) is a major health-care concern worldwide. This can manifest itself in many distinct forms the transition from clinically indolent PCa to more invasive aggressive form remains poorly understood. It now universally accepted that glycan expression patterns change with cellular modifications accompany onset tumorigenesis. aim this study was investigate if differential glycosylation could distinguish between indolent, significant, PCa. Whole...