Molecular Studies Of The Astrocyte Reservoir Of HIV-1 In The Central Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$592,661.00
Summary
HIV infects the brain causing dementia in 10-20% patients. Strategies aimed at eradicating HIV infection fail to take into account CNS infection. Understanding the way in which HIV enters, infects and replicates in the brain is pivotal in development of drugs to prevent brain infection and dementia. Our studies have shown that HIV infection of the brain involves mechanisms distinct to those observed for blood and other organs. This study seeks to clarify such mechanisms.
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
Role Of Brm In Skin Tumour Progression From Benign To Malignant
Funder
National Health and Medical Research Council
Funding Amount
$457,267.00
Summary
Australia has the highest incidence of skin cancer in the world. Skin cancer is 3 times as common as all other cancers combined and continues to increase in incidence, particularly in the aging population. Skin cancer is caused by exposure to the ultraviolet radiation found in sunlight. Ultraviolet radiation causes the appearance of solar keratosis, or sunspots, benign lesions that are not particularly dangerous to human health. Some of these develop into malignant squamous cell carcinomas that ....Australia has the highest incidence of skin cancer in the world. Skin cancer is 3 times as common as all other cancers combined and continues to increase in incidence, particularly in the aging population. Skin cancer is caused by exposure to the ultraviolet radiation found in sunlight. Ultraviolet radiation causes the appearance of solar keratosis, or sunspots, benign lesions that are not particularly dangerous to human health. Some of these develop into malignant squamous cell carcinomas that can spread to other tissues and are potentially fatal. Little is known about the biological mechanisms involved in solar keratosis development into squamous cell carcinomas. We have identified the gene brm as being involved in this process. It has not previously been recognised that this gene is important for skin cancer development and therefore our preliminary studies have identified a potential new target. We will study the role of this gene in ultraviolet radiation induced skin carcinogenesis, determine whether it is mutated by ultraviolet radiation in human skin cancer, and what role in plays in some key biological processes in skin cancer development. This study will expand our understanding of malignant conversion during human skin carcinogenesis, the most prevalent human cancer in Australia.Read moreRead less
Cell Type Specific Biologic Responses To HIV Infection
Funder
National Health and Medical Research Council
Funding Amount
$636,242.00
Summary
The way in which HIV alters the internal environment of its target cells to facilitate its growth will be examined. These changes enhance its ability to gain a toehold in the human body after entering the genital tract and its persistence for life in the brain and elsewhere in the body.
The Diagnosis Of Obstructive Sleep Apnea In Primary Care
Funder
National Health and Medical Research Council
Funding Amount
$295,075.00
Summary
The gold standard method for diagnosis of sleep apnea is the overnight sleep study. These tests are expensive, have long waiting lists and are hard to access outside larger cities. We aim to determine if general practitioners can combine information from questionnaires and a simple home diagnostic test, to confirm or rule out sleep apnea. The results of this study will eventually lead to more accessible and efficient diagnosis and treatment of this common condition.
Interactions Between HIV And Mycobacterial Infections Of Macrophages Mediated By Changes In Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$119,625.00
Summary
HIV-AIDS and tuberculosis are two of the worlds most important diseases. HIV-AIDS is the fourth leading killing disease worldwide and tuberculosis is the leading opportunistic infection in patients with AIDS particularly in the developing world. Both microbes infect the same cell type, the macrophage, which is widely distributed throughout the body, particularly in lymph nodes and lung. Recent studies in humans have shown that HIV and TB like organisms stimulate each others growth. This study us ....HIV-AIDS and tuberculosis are two of the worlds most important diseases. HIV-AIDS is the fourth leading killing disease worldwide and tuberculosis is the leading opportunistic infection in patients with AIDS particularly in the developing world. Both microbes infect the same cell type, the macrophage, which is widely distributed throughout the body, particularly in lymph nodes and lung. Recent studies in humans have shown that HIV and TB like organisms stimulate each others growth. This study uses the immense power of DNA microarrays, based on the identification of almost all genes by the human genome project, to decipher the interactions between the two microbes. By following up new leads indicated by the microarrays, the way in which the microbes manipulate the macrophage to enhance their own growth and that of the other can be eventually deciphered. This will provide new strategies for future interventions. New drugs are urgently needed for both microbes.Read moreRead less
The Role Of Chemokines In Establishing HIV Latency
Funder
National Health and Medical Research Council
Funding Amount
$372,049.00
Summary
Although antiviral therapy is effective in controlling HIV, therapy must be continued life-long because the virus cannot be cleared from long lived infected CD4+ T cells that are silently or latently infected. In this proposal we will explore the mechanism of how HIV can enter these resting CD4+ T-cells and establish long lived latent infection. Understanding this process may potentially lead to new strategies to cure HIV infection.
Interactions Between Herpes Simplex Viral And Neuronal Motor Proteins
Funder
National Health and Medical Research Council
Funding Amount
$222,962.00
Summary
Herpes simplex virus (HSV) lies dormant within the nerve cell bodies near the spinal cord in most people. Intermittently the virus reactivates and is transported down the nerve to the skin where it causes blisters-ulcers or is shed without causing symptoms. The aim of this grant is to determine how Herpes Simplex virus is transported within nerve cells at the molecular level. It builds on recent discoveries of a direct interaction between a Herpes simplex viral protein and the nerve cell motor p ....Herpes simplex virus (HSV) lies dormant within the nerve cell bodies near the spinal cord in most people. Intermittently the virus reactivates and is transported down the nerve to the skin where it causes blisters-ulcers or is shed without causing symptoms. The aim of this grant is to determine how Herpes Simplex virus is transported within nerve cells at the molecular level. It builds on recent discoveries of a direct interaction between a Herpes simplex viral protein and the nerve cell motor protein which transports essential components down nerves from the spinal cord to the skin. Ultimately we aim to develop inhibitors of this process which might be candidates for further development as antivirals for control of recurrent herpes simplex.Read moreRead less
Assembly And Transport Of Herpes Simplex Virus Within Neurones
Funder
National Health and Medical Research Council
Funding Amount
$475,500.00
Summary
Herpes simplex virus (HSV) enters the human body via the skin before entering the termini of nerve cell processes. It is transported along these processes to the body of the nerve cell. HSV lies dormant within these nerve cell bodies near the spinal cord in most people. Intermittently the virus reactivates and is transported back down the nerve cell processes to the skin where it causes blisters-ulcers or is shed without causing symptoms. The aim of this grant is to determine how HSV is transpor ....Herpes simplex virus (HSV) enters the human body via the skin before entering the termini of nerve cell processes. It is transported along these processes to the body of the nerve cell. HSV lies dormant within these nerve cell bodies near the spinal cord in most people. Intermittently the virus reactivates and is transported back down the nerve cell processes to the skin where it causes blisters-ulcers or is shed without causing symptoms. The aim of this grant is to determine how HSV is transported and assemblied within nerve cells at the molecular level. Recent discoveries have shown how virus transport in nerve cells is dependent on interactions between specific viral proteins and cellular motor proteins. Such information on viral transport and assembly mechanisms will allow development of inhibitors of these processes which may be candidates for use as antivirals for control of recurrent herpes simplex. In addition, this information will allow the virus to be exploited for use in gene therapy to introduce DNA into human nerve cells to correct genetic abnormalities.Read moreRead less