Induction Of Antigen-specific Humoral Tolerance By RAAV-mediated Delivery Of CTLA4-Ig-antigen Fusion Molecules
Funder
National Health and Medical Research Council
Funding Amount
$524,456.00
Summary
There are many medical situations where immune suppression is required. Available methods lack specificity and risk infection, drug-related side-effects and cancer. We have discovered a novel way of suppressing immunity such that only unwanted responses are eliminated. This involves virus-mediated delivery of antigen fused to CTLA4-Ig. We plan to test this strategy in the context of gene therapy, to work out how it works and to optimise the approach. Success will have broad health implications.
Peptidase Inhibitor 16: A New Biomarker For Human Treg
Funder
National Health and Medical Research Council
Funding Amount
$391,262.00
Summary
As autoimmune diseases including type 1 diabetes and IBD are on the increase, there is still great need for novel diagnostic or therapeutic molecules. We have discovered a novel role for a protein called PI16, which we believe is a biomarker for natural regulatory T cells. These cells police the immune system, preventing inappropriate immune responses such as those that cause autoimmune diseases. This project will confirm its suitability for use as a diagnostic or therapeutic biomarker.
Nuclear Import Of The HIV-1 Pre-integration Complex: Mechanism And Therapeutic Implications
Funder
National Health and Medical Research Council
Funding Amount
$425,250.00
Summary
The human immunodeficiency virus (HIV) has a unique feature distinguishing it from other retroviruses the ability to replicate in non-dividing cells such as in macrophage-microglia cells which are among the prime target cells for virus infection. The viral genome needs to be integrated into the host cell chromosome in order to infect cells productively. The host cell s genome is not normally accessible because it is located inside the nucleus, separated from the rest of the cell by the barrier o ....The human immunodeficiency virus (HIV) has a unique feature distinguishing it from other retroviruses the ability to replicate in non-dividing cells such as in macrophage-microglia cells which are among the prime target cells for virus infection. The viral genome needs to be integrated into the host cell chromosome in order to infect cells productively. The host cell s genome is not normally accessible because it is located inside the nucleus, separated from the rest of the cell by the barrier of the nuclear envelope (NE). However, HIV has found a way to transport its genome to the nucleus in a complex together with other viral-cellular proteins, the pre-integration complex (PIC), through the intact NE of non-dividing cells. This is a crucial step of viral infection and if blocked could prevent the establishment and spread of HIV infection. Thus far it is unclear how the large HIV PIC accesses the nucleus and which viral and cellular proteins are essential for the navigation of the PIC through the NE and into the nucleus. Using fluorescent labels on the key components of the HIV PIC including the DNA in combination with confocal laser scanning microscopy and a novel optical single-transporter recording technique, we will be able to visualize the PIC on its way through the NE for the first time. Mutational analyses will further identify the key residues of viral proteins and the cellular nuclear transport machinery utilized during the transport. The results of this study will literally provide a clear picture of nuclear import of the HIV PIC. The future aim of elucidating this essential step in HIV replication is to identify new targets for anti-retroviral drug interventions that may be less prone to side effects and development of resistance than the currently available drug regimens.Read moreRead less
Pharmacological Targeting Via AKT, PTEN, And TGF-beta Pathway Integration Using Novel Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$634,875.00
Summary
We have identified potentially important interactions of cellular pathways that vary between individual sufferers, but which also provide common molecular targets for novel drug development. Our suite of novel and potent drugs that markedly and selectively inhibit cancer cell growth will be studied to determine if these pharmaceutical agents act to inhibit tumour cell proliferation by targeting common effector molecules of integrated cellular pathways.
The Role And Underlying Mechanisms Of Constitutional Epigenetic Silencing In Cancer Predisposition
Funder
National Health and Medical Research Council
Funding Amount
$218,617.00
Summary
Familial and young onset bowel and uterine cancer are usually caused by the inheritance of spelling mistakes in the genetic code within a set of cancer-protection genes. Recently, some patients were identified with their gene switched off by paralysing chemicals instead. This study aims to identify additional cancer cases with gene paralysis, determine if this arises in the presence or absence of a genetic change in front of the gene, and how gene paralysis is transmitted to the next generation.
Mechanisms Of Head And Neck Cancer Progression Role Of Matrix Metallopreinase (MMP-2) Using In Vitro And In Vivo Anima
Funder
National Health and Medical Research Council
Funding Amount
$218,668.00
Summary
This proposal will assist in improving human health, quality of life and patient lifespan. Head and Neck cancer is of high prevalence in Australia and China. Cancer patients, often with metastasis to adjacent and distant organs, including bone at late stages of the disease, suffer from pain, facial nerve paralysis, recurrence and frequently die under very distressing circumstances. This proposal intends to elucidate the molecular mechanism of Head and Neck cancer and help come up with better tre ....This proposal will assist in improving human health, quality of life and patient lifespan. Head and Neck cancer is of high prevalence in Australia and China. Cancer patients, often with metastasis to adjacent and distant organs, including bone at late stages of the disease, suffer from pain, facial nerve paralysis, recurrence and frequently die under very distressing circumstances. This proposal intends to elucidate the molecular mechanism of Head and Neck cancer and help come up with better treatments against cancers including providing a new target for cancer gene therapy.Read moreRead less