Molecular Mechanisms Of Varicella Zoster Virus Interactions With Key Target Cells
Funder
National Health and Medical Research Council
Funding Amount
$421,650.00
Summary
Varicella zoster virus (VZV) is a herpesvirus which infects up to 90% of the population. VZV causes chickenpox (varicella) predominantly in childhood and shingles (herpes zoster) in middle to old age people. Whilst VZV usually causes relatively mild disease in healthy individuals, VZV still causes significant morbidity in children and adults. VZV causes life-threatening disease in immunocompromised individuals such as patients who are elderly or have HIV disease . Herpes zoster affects many eder ....Varicella zoster virus (VZV) is a herpesvirus which infects up to 90% of the population. VZV causes chickenpox (varicella) predominantly in childhood and shingles (herpes zoster) in middle to old age people. Whilst VZV usually causes relatively mild disease in healthy individuals, VZV still causes significant morbidity in children and adults. VZV causes life-threatening disease in immunocompromised individuals such as patients who are elderly or have HIV disease . Herpes zoster affects many ederly individuals and a major complication is prolonged severe pain or post-herpetic neuralgia (PHN), both severely debilitating and which often requires follow-up medical care for months or years after the initial attack. Despite its significant impact on the community, little is known about the molecular details of how this virus functions. This project aims to improve our understanding of how VZV infection affects specialised human cells in order to make further advances in antiviral therapies as well improve vaccine design for the treatment or prevention of VZV disease and the crippling complication of PHN. This project has four components: (1) We will continue studies which have shown that VZV may actively avoid detection by the immune system. We aim to identify the mechanism and viral genes responsible for interfering with the expression of molecules which are essential for our immune system. (2) We will determine whether VZV infection of specialised immune cells (called dendritic cells) will affect their ability to function and interact with other immune cells (called T cells). (3) We will examine how VZV interacts in human nerve cells (neurons) and whether infected neurons undergo specially programmed cell death (apoptosis). (4) We will examine how different human cells change when they are infected with VZV. A new and exciting technology called DNA microarray now makes it possible to examine the expression of many thousands of genes in one experiment.Read moreRead less
Pushing AR Toward Better Outcomes In Breast And Prostate Cancers
Funder
National Health and Medical Research Council
Funding Amount
$998,754.00
Summary
Breast and prostate cancers kill >6000 Australians each year. These cancers are strikingly similar, both driven by hormone receptors that have ‘gone bad’. Current therapies aim to eradicate the receptors. While often effective, therapeutic resistance is common and results in fatal disease. We aim to develop new, less toxic treatments that switch receptor behaviour from good to bad, without destroying them. This should improve quality of life, while preventing drug resistance and loss of lives ....Breast and prostate cancers kill >6000 Australians each year. These cancers are strikingly similar, both driven by hormone receptors that have ‘gone bad’. Current therapies aim to eradicate the receptors. While often effective, therapeutic resistance is common and results in fatal disease. We aim to develop new, less toxic treatments that switch receptor behaviour from good to bad, without destroying them. This should improve quality of life, while preventing drug resistance and loss of lives.Read moreRead less
Why Is The Bone Marrow A “hot-spot” For Myeloma Plasma Cell Metastasis: Are There Gremlins In The System?
Funder
National Health and Medical Research Council
Funding Amount
$651,979.00
Summary
Most cancer patients die because their cancer spreads from a primary site to other tissues in the body. Once escaping the primary site, 70% of all tumours will spread to bone. This raises the question, why is bone a preferred destination for cancer cells? We provide evidence that Gremlin1, made by non-cancer cells within bone, is a key protein that supports cancer growth. This study will examine whether inhibiting Gremlin1 is a potential therapy to inhibit cancer spreading to bone.
Targeting Microtubules To Overcome Chemoresistance In Pancreatic Cancer
Funder
National Health and Medical Research Council
Funding Amount
$594,336.00
Summary
Pancreatic cancer is a devastating disease with a dismal prognosis because it is extremely resistant to chemotherapy agents. We plan to examine the expression of proteins called microtubules in pancreatic cancer and assess their role in drug resistance. It is anticipated that the findings of these studies will lead to the development of effective approaches to sensitise the cancer cells to chemotherapy agents.
Targeting Tumour-Stromal Interactions In Pancreatic Cancer
Funder
National Health and Medical Research Council
Funding Amount
$410,095.00
Summary
Pancreatic cancer claims five Australian lives every day and is one of the nations most lethal diseases. Despite aggressive treatment regimes, there has been no improvement in patient survival in the last decade. Evidence suggests that targeting cancer cells alone is not enough. The intense stromal reaction inhibits drug delivery and increases the aggressiveness of the tumours. Thus, depletion of the stroma or pancreatic stellate cells is a potential therapeutic target.
Mammalian chitinases and gene therapy: new weapons to combat fungal and insect attack in mammals. Plants combat fungal and insect attack by producing chitin degrading enzymes. Related, chitinolytic enzymes have been identified in mammals, but their functions are unclear. We found that chitinases from human macrophages inhibited fungal growth. We hypothesise that, like plants, mammalian chitinases are produced to fight chitin containing pathogens. We will transform cells with a chitotriosidase ge ....Mammalian chitinases and gene therapy: new weapons to combat fungal and insect attack in mammals. Plants combat fungal and insect attack by producing chitin degrading enzymes. Related, chitinolytic enzymes have been identified in mammals, but their functions are unclear. We found that chitinases from human macrophages inhibited fungal growth. We hypothesise that, like plants, mammalian chitinases are produced to fight chitin containing pathogens. We will transform cells with a chitotriosidase gene and encapsulate them, creating bioreactors secreting chitinases. Therapeutic effects will be tested by grafting bioreactors to mice inoculated with Aspergillus. The research is a new approach to fighting chitin containing pathogens, with potential applications from parasite infestations in livestock to fungal infections in humans.Read moreRead less
Levelling the Playing Field: Starting with the School Playground. This project aims to demonstrate the effectiveness of simple, cost-effective programs for changing the way parents and teachers view manageable risk-taking for children with disabilities and increasing the level of responsibility that children take for their own actions. The well-being of all children with disabilities is at risk and the gap continues to widen. New programs, such as the National Disability Insurance Scheme, will p ....Levelling the Playing Field: Starting with the School Playground. This project aims to demonstrate the effectiveness of simple, cost-effective programs for changing the way parents and teachers view manageable risk-taking for children with disabilities and increasing the level of responsibility that children take for their own actions. The well-being of all children with disabilities is at risk and the gap continues to widen. New programs, such as the National Disability Insurance Scheme, will place increasing demands on young people with disabilities. Innovative approaches are desperately. Such programming must begin early, by including children in an age-appropriate ways and simultaneously addressing the issues of adults who have the most significant influence: parents and teachers.Read moreRead less
The Role Of Melanoma Tumour Antigen P97 (Melanotransferrin) In Melanoma Tumourigenesis.
Funder
National Health and Medical Research Council
Funding Amount
$563,242.00
Summary
The Role of Melanoma Tumour Antigen p97 (Melanotransferrin) in Melanoma Tumourigenesis Melanotransferrin (MTf) is a homologue of the iron transport protein, transferrin, and was one of the first well characterised melanoma tumour antigens. Our published studies have shown that MTf plays an important role in melanoma tumourigenesis in vivo. In this proposal, we will assess if it is associated with melanoma progression in patient samples and examine its role in melanoma growth and metastasis.
The Immunoregulatory Role of the Endogenous Cannabinoid Anandamide. Anandamides are naturally occurring fatty acids that act at the cannabinoid receptor expressed in the brain and periphery. A new proposal by our research group challenges traditional models of the disease process by suggesting that the anandamide system is an important imunoregulatory system that can be targeted by invading pathogens. We propose that disruption to the anandamide system, by bacteria or viruses acting at the rece ....The Immunoregulatory Role of the Endogenous Cannabinoid Anandamide. Anandamides are naturally occurring fatty acids that act at the cannabinoid receptor expressed in the brain and periphery. A new proposal by our research group challenges traditional models of the disease process by suggesting that the anandamide system is an important imunoregulatory system that can be targeted by invading pathogens. We propose that disruption to the anandamide system, by bacteria or viruses acting at the receptor to block immunological responses, contributes to chronic illness states. At this point we have good evidence that anandamides are immunoregulators, however, we have very little knowledge of their precise physiological role. The aim of this research is to begin to characterise the immunoregulatory role of the anandamide system. This project will provide a comprehensive understanding of this endogenous control system, the immunological properties of which have not previously been described. The outcome of this research may lead to the identification of new avenues for the development of pharmaceutical interventions that can target this system.Read moreRead less
Development of Acid Degradable Polymeric Nanoparticles for Intracellular and Tumour Site Selective Delivery of Drugs. There is an enormous need to develop effective anticancer drug delivery systems to reduce the social and economic impact of cancer. One of the most critical problems in tumour treatment is the lack of selective toxicity of anticancer drugs against tumour tissues. Our multidisciplinary team will aim to develop a novel polymer based system for tumour site-selective delivery of anti ....Development of Acid Degradable Polymeric Nanoparticles for Intracellular and Tumour Site Selective Delivery of Drugs. There is an enormous need to develop effective anticancer drug delivery systems to reduce the social and economic impact of cancer. One of the most critical problems in tumour treatment is the lack of selective toxicity of anticancer drugs against tumour tissues. Our multidisciplinary team will aim to develop a novel polymer based system for tumour site-selective delivery of anticancer drugs. Development of such advanced drug delivery systems will significantly enhance Australia`s power in biotechnology. Development and/or formation of strategies to improve the health quality of Australians, is an important anticipated outcome of this innovative project.Read moreRead less