A5019278749- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- SARS-CoV-2 and COVID-19 Research
- Pancreatic function and diabetes
- T-cell and Retrovirus Studies
- COVID-19 Clinical Research Studies
- vaccines and immunoinformatics approaches
- Galectins and Cancer Biology
- Nanoparticles: synthesis and applications
- Cytokine Signaling Pathways and Interactions
- Nicotinic Acetylcholine Receptors Study
- Viral gastroenteritis research and epidemiology
- Virus-based gene therapy research
- Child Nutrition and Water Access
- Vaccine Coverage and Hesitancy
- Graphene and Nanomaterials Applications
- Immunodeficiency and Autoimmune Disorders
- Animal Virus Infections Studies
- Long-Term Effects of COVID-19
- Marine Sponges and Natural Products
- Genetics and Neurodevelopmental Disorders
- SARS-CoV-2 detection and testing
- Marine Invertebrate Physiology and Ecology
Westmead Institute for Medical Research
2023-2024
Australian Institute of Tropical Health and Medicine
2020-2022
James Cook University
2020-2022
QIMR Berghofer Medical Research Institute
2021
Cardiff University
2014-2018
University Hospital of Wales
2018
University of Bath
2013
University of Minnesota
2013
Antigen recognition by the T-cell receptor (TCR) is a hallmark of adaptive immune system. When TCR engages peptide bound to restricting major histocompatibility complex molecule (pMHC), it transmits signal via associated CD3 complex. How extracellular antigen event leads intracellular phosphorylation remains unclear. Here, we used single-molecule localization microscopy quantify organization TCR-CD3 complexes into nanoscale clusters and distinguish between triggered nontriggered complexes....
Summary Fluorochrome-conjugated peptide–major histocompatibility complex (pMHC) multimers are widely used for flow cytometric visualization of antigen-specific T cells. The most common multimers, streptavidin–biotin-based ‘tetramers’, can be manufactured readily in the laboratory. Unfortunately, there large differences between threshold cell receptor (TCR) affinity required to capture pMHC tetramers from solution and that which is activation. This disparity means sometimes fail stain cells...
Abstract Peptide-MHC (pMHC) multimers, usually used as streptavidin-based tetramers, have transformed the study of Ag-specific T cells by allowing direct detection, phenotyping, and enumeration within polyclonal cell populations. These reagents are now a standard part immunology toolkit been in many thousands published studies. Unfortunately, TCR-affinity threshold required for staining with pMHC multimer protocols is higher than that efficient activation. This discrepancy makes it possible...
In type 1 diabetes, cytotoxic CD8+ T cells with specificity for β cell autoantigens are found in the pancreatic islets, where they implicated destruction of insulin-secreting cells. contrast, disease relevance cell–reactive that detectable circulation, and their relationship to function, not known. Here, we tracked multiple, circulating subsets measured function longitudinally 2 years, starting immediately after diagnosis diabetes. We change cell–specific effector memory expressing CD57 was...
Fluorochrome-conjugated peptide-MHC (pMHC) multimers are commonly used in combination with flow cytometry for direct ex vivo visualization and characterization of Ag-specific T cells, but these reagents can fail to stain cells when TCR affinity and/or cell-surface density low. pMHC multimer staining tumor-specific, autoimmune, or MHC class II-restricted be particularly challenging, as tend express relatively low-affinity TCRs. In this study, we attempted improve using anti-fluorochrome...
The three transcription factors, PDX1, NGN3 and MAFA, are very important in pancreatic development. Overexpression of these factors can reprogram both exocrine cells SOX9-positive the liver into resembling beta cells. In this study we investigate whether other cell types be reprogrammed. Eight compared results consistent with idea that reprogramming occurs to a greater degree for developmentally related (pancreas, liver) than types, such as fibroblasts. Using line mouse hepatocyte-derived...
There is increasing evidence that induction of local immune responses a key component effective vaccines. For respiratory pathogens, for example tuberculosis and influenza, aerosol delivery being actively explored as method to administer vaccine antigens. Current animal models used study pathogens suffer from anatomical disparity with humans. The pig natural important host influenza viruses physiologically more comparable humans than other in terms size, tract biology volume. It may also be...
Polypeptide vaccines effectively activate human T cells but suffer from poor biological stability, which confines both transport logistics and in vivo therapeutic activity. Synthetic biology has the potential to address these limitations through generation of highly stable antigenic "mimics" using subunits that do not exist natural world. We developed a platform based on D–amino acid combinatorial chemistry used this reverse engineer fully artificial CD8+ cell agonist mirrored immunogenicity...
The prevalence of autoimmune diseases is on the rise globally. Currently, autoimmunity presents in over 100 different forms and affects around 9% world's population. Current treatments available for are inadequate, expensive, tend to focus symptom management rather than cure. Clinical trials have shown that live helminthic therapy can decrease chronic inflammation associated with inflammatory bowel disease other gastrointestinal conditions. As an alternative better controlled approach...
Identifying SARS-CoV-2-specific T cell epitope-derived peptides is critical for the development of effective vaccines and measuring duration specific SARS-CoV-2 cellular immunity. In this regard, we previously identified within topologically structurally essential regions spike nucleocapsid proteins by applying an immunoinformatics pipeline. study, selected 30 spike- nucleocapsid-derived assessed whether these induce responses avoid major mutations found in variants concern. Our peptide pool...
Marine organisms produce a diverse range of toxins and bioactive peptides to support predation, competition, defense. The peptide repertoires stony corals (order Scleractinia) remain relatively understudied despite the presence tentacles used for predation defense that are likely contain compounds. Here, we show tentacle extract from mushroom coral, Heliofungia actiniformis, contains numerous with molecular weights analogous venom profiles species such as cone snails. Using NMR spectroscopy...
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Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic, progressive, and growing worldwide health burden associated with mounting morbidity, mortality, economic costs. Improvements in NTM-PD management are urgently needed, which requires better understanding of fundamental immunopathology. Here, we examine temporal dynamics the immune compartment during caused by Mycobacterium avium complex (MAC) Mycobactereoides abscessus (MABS). We show that active MAC infection...