Role Of The CD8-Heparan Sulfate Interaction In CD8+ T Cell Development And Function
Funder
National Health and Medical Research Council
Funding Amount
$649,135.00
Summary
The immune system can recognise a large array of foreign pathogens without reacting to self-components. For this to occur T cells, the main mediators of immunity, must be made to tolerate self-molecules as they develop in the thymus. We have identified a novel interaction between a molecule called CD8 on T cells and a complex carbohydrate called heparan-sulfate, which helps auto-reactive T cells to be eliminates in the thymus. The aim of this project is to further investigate this phenomenon.
Using Influenza Vaccination To Understand And Improve Anti-viral Immunity In COPD
Funder
National Health and Medical Research Council
Funding Amount
$1,316,597.00
Summary
Chronic obstructive pulmonary disease (COPD) is one of the leading causes of mortality and morbidity worldwide. Lung infections often make those afflicted by COPD very unwell. We have recently shown that influenza vaccination induces a poor antibody response in many COPD patients. This study will examine why this is the case, and what can be done to restore normal immune function. In the final year of the Project, we will assess whether doubling the dose of influenza vaccination is helpful.
Multiple Paths Of TFH Differentiation And Their Impact On B Cell Protection Against Infection
Funder
National Health and Medical Research Council
Funding Amount
$923,466.00
Summary
Collaboration between T and B cells is crucial for immune protection and underpins current vaccine strategies. We have revealed an unappreciated flexibility that exists in T cell responses which varies the instructions they give B cells. It is likely this tailors immune responses to ensure protection to countless infectious diseases. This project uses cutting-edge technologies to understand this flexibility and has important implications for vaccine design and treatment of infectious disease.
An Investigation Into The Adaptive Immune Response In Celiac Disease
Funder
National Health and Medical Research Council
Funding Amount
$597,167.00
Summary
Celiac Disease (CD), an autoimmune-like disease that is triggered by the ingestion of dietary wheat gluten, or related proteins from rye and barely, affects ~1% of the population, causing tissue damage in the small intestine. The only available treatment is strict adherence to a lifelong gluten free diet. Our project aims to understand, at the molecular level, how components of the immune system and gluten interact to trigger the immune response that leads to CD symptoms.
Vaccines that deposit memory T cells within the lung, gut and genital tract hold enormous therapeutic potential, as these mucosal surfaces are major portals of entry into the body for many viruses. However, the accumulation of large numbers of T cells within the mucosal tissue may increase the number of target cells for T cell trophic viruses (eg HIV) to infect. We will explore factors that result in the generation of mucosal memory T cells that are resistant to virus infection.
Epigenetic Therapies As Molecular Probes To Investigate The Molecular Pathogenesis Of Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$937,402.00
Summary
A major limitation to the success of targeted therapies in cancer is the fact that we have few if any tools to study in detail their mechanism of action within cancerous and normal cells. If we were able to visualise these drugs within cells and precisely characterise the proteins, DNA and RNA within a cell that interact with these therapies we will be able to identify strategies that can optimise their efficacy and reduce the side-effects of these treatments.
VCAM-targeted Delivery Of Recombinant CD39 To The Endothelium Is Antithrombotic, Antiinflammatory And Ameliorates Ischaemia Reperfusion Injury.
Funder
National Health and Medical Research Council
Funding Amount
$623,327.00
Summary
Blockage of arteries with clots leads to heart attacks and strokes. Reestablishment of blood supply by clot-busting drugs or mechanical interventions paradoxically causes further organ injury. This is due to toxic chemicals generated by inflammatory processes and free oxygen radicals. We have created an unique drug that selectively targets blood vessels that are injured by process. The drug will deliver blood-thinning activity and reduce inflammatory stress selectively at the site of need.
A Pharmacological Targeting Approach Implementing Albumin As A Carrier Of A Novel Chemotherapeutic
Funder
National Health and Medical Research Council
Funding Amount
$560,659.00
Summary
New drugs for cancer therapy are essential to develop that overcome resistance to standard chemotherapeutics. We have developed potent anti-cancer chelators that bind to the abundant plasma protein, albumin. Our studies showed increased tumour cell uptake of the chelator, Dp44mT, mediated by albumin. We will elucidate the mechanisms of their albumin-mediated uptake, with the aim to implement albumin nanoparticles as carriers of novel chelators to selectively target tumours.
Inflammation And Oxidative Stress In Emerging Psychotic And Mood Disorders
Funder
National Health and Medical Research Council
Funding Amount
$432,619.00
Summary
We are conducting four large clinical trials testing anti-inflammatory treatments like ?-3 PUFAs and aspirin in young people who are at high-risk for psychosis or have depression. This proposal adds an important component to this research by investigating inflammatory and oxidative stress markers. We aim to determine if the investigated biomarkers predict the course of illness and response to treatments. The findings will facilitate early intervention and targeted treatment.
Molecular Profiling Residual Disease From Early Stage HER2 Positive Breast Cancer Treated With Neoadjuvant Chemo- And Anti-HER2 Therapy
Funder
National Health and Medical Research Council
Funding Amount
$467,108.00
Summary
Chemotherapy given prior to surgery can often inform us if a breast tumour is sensitive or resistant to therapy by the amount of disease remaining at time of surgery. We have further shown that the immune response is also important in these patients. In this study we propose to analyse the tumour samples that remain after chemotherapy in order to understand possible resistance mechanisms as well as how the immunity influences survival of HER2-positive breast cancer patients