Identification Of The Molecular Genetic Basis Of The Hepatic Veno-occlusive Disease With Immunodeficiency Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$224,250.00
Summary
One of the most serious complications of bone marrow transplantation is veno-occlusive disease (VOD), also termed sinusoidal obstruction syndrome (SOS). This condition occurs in 10% of transplanted patients and is characterised by abnormalities of liver function, enlargement of the liver, clotting abnormalities, fluid retention and finally failure of multiple organs and death in 30-50% of cases. The cause of VOD is unknown, and its occurrence cannot be predicted in individual patients. Eight fam ....One of the most serious complications of bone marrow transplantation is veno-occlusive disease (VOD), also termed sinusoidal obstruction syndrome (SOS). This condition occurs in 10% of transplanted patients and is characterised by abnormalities of liver function, enlargement of the liver, clotting abnormalities, fluid retention and finally failure of multiple organs and death in 30-50% of cases. The cause of VOD is unknown, and its occurrence cannot be predicted in individual patients. Eight families have been described in whom a number of individuals have succumbed to a condition which is clinically and histologically indistinguishable from VOD. Affected individuals also have a form of immunodeficiency (hence termed VODI), and the abnormalities are inherited in an autosomal recessive pattern. All eight are of Lebanese origin, suggesting that a single genetic ancestral mutation was responsible for the disorder in all families, who are distantly related. We have access to genetic material from three of these families, and are on the way to identifying the causative genetic abnormality. We hypothesise that understanding this abnormality will lead to an understanding of VOD which occurs after bone marrow transplantation. We have used 800 polymorphic genetic markers scattered throughout the genome to identify the location of the genetic abnormality, and have localised the defect to a region of chromosome 2 which contains approximately 37 known and predicted genes. We now aim to determine which of the gene(s) in the candidate region is responsible for VODI, and plan to examine DNA from individuals who have had VOD after transplantation to determine if they have a related abnormality. Finding the VODI gene will benefit these families through the availability of carrier detection and may also lead to an understanding of the veno-occlusive disease that occurs after bone marrow transplantation.Read moreRead less
Heritable Influences In Experimental Retinopathy Of Prematurity
Funder
National Health and Medical Research Council
Funding Amount
$272,591.00
Summary
Retinopathy of prematurity is an eye disease of very premature infants who require neonatal intensive care. It is a major cause of childhood blindness world-wide. Disease is caused by the growth of abnormal blood vessels in the retina, at the back of the eye. Currently, management involves the repeated examination of premature infants by an eye doctor. The babies are anaesthetized for this examination. If early disease is detected, then the affected eyes are treated with a medical laser, to burn ....Retinopathy of prematurity is an eye disease of very premature infants who require neonatal intensive care. It is a major cause of childhood blindness world-wide. Disease is caused by the growth of abnormal blood vessels in the retina, at the back of the eye. Currently, management involves the repeated examination of premature infants by an eye doctor. The babies are anaesthetized for this examination. If early disease is detected, then the affected eyes are treated with a medical laser, to burn the abnormal blood vessels. This stops the growth of these vessels and can prevent the child from going blind. However, the laser treatment itself can damage the eye. Left untreated, early retinopathy of prematurity will disappear of its own accord in some babies, but because they cannot currently be distinguished from those who will develop severe disease, all babies with signs of disease are treated. Not every premature infant develops retinopathy of prematurity: an as-yet unknown genetic factor controls susceptibility to disease. We plan to investigate this genetic basis using laboratory rats. Raised under the same conditions that are used in intensive care nurseries, baby rats develop eye disease that is similar to retinopathy of prematurity. However, as with human babies, not every baby rat develops this eye disease. We have shown a heritable tendency to retinopathy in different strains of rat. We identify the genes and proteins that differ amongst rats with or without the eye disease. We predict that identification of the inherited factors for retinopathy of prematurity in rats will provide strong clues to similar factors in humans. Our ultimate goal is to develop a test which will identify those human babies who are at risk of developing blinding retinopathy of prematurity, so that treatment is not given unnecessarily. We also expect to discover new targets for treatment.Read moreRead less
The Human Immunodeficiency Virus (HIV) is a virus that infects and kills the cells of your immune system. This infection eventually leads to the Acquired Immune Deficiency Syndrome (AIDS). An important aspect in preventing infection is to study how HIV enters immune cells and how infection spreads. Our lab is researching drugs to block the entry of HIV in immune cells, which can hopefully be used together with existing anti-HIV drugs to slow down the spread of the virus and the onset of AIDS.
Elucidating The Flexibility Of Coreceptor Engagement By HIV-1 Important For Macrophage Tropism And Escape From Entry Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$635,506.00
Summary
CCR5 antagonists are a new type of anti-HIV-1 drug that stops the virus from entering cells. We have evidence to suggest that the ability of CCR5 antagonists to function properly is linked to the ability of HIV-1 to infect a type of immune cell called macrophages. In this proposal, we will investigate precisely how HIV-1 enters macrophage cells, and then determine how this may influence the outcome of patients who are receiving these drugs as part of their clinical care.
Prevention Of HIV-1 Infection By Adeno Associated Virus Vector-delivered Broadly Neutralizing Antibodies Or Antibody-like Molecules
Funder
National Health and Medical Research Council
Funding Amount
$875,854.00
Summary
A promising neutralizing molecule has boosted hopes of an HIV vaccine. It remains unknown how well this molecule prevents HIV infection under conditions reflecting “real world” exposure, including exposure to HIV in the form of cells carrying virus or free-floating virus in the presence of semen. We will assess this molecule for their ability to inhibit transmission of HIV-like viruses under these conditions. These experiments will define requirements to protect against HIV infection.
A Novel RNA Repressor Element Regulates HIV-1 Replication
Funder
National Health and Medical Research Council
Funding Amount
$341,453.00
Summary
HIV-1 causes acquired immunodeficiency syndrome, with up to 40 million infected people and 5 million infected annually. The spatio-temporal regulation of HIV-1 reverse transcription has recently been recognised as a possible new drug target. Our research has revealed a novel repressor of reverse transcripiton (RRT). The RRT plays a major role in regulating the spatio-temporal regulation of reverse transcripiton. Targetting the RRT function would be a novel means to combat HIV-1 infection.
Addressing The Major Challenges In HIV Vaccine And Cure Research
Funder
National Health and Medical Research Council
Funding Amount
$16,136,755.00
Summary
HIV remains one of the defining global health challenge of our times. 37 million people are living with HIV with 2 million new infections each year. Despite advances in management of HIV infection with antiretroviral therapy, there is still no cure, no effective vaccine, and several co-infections reduce life expectancy. This program assembles Australia’s leading HIV researchers to use innovative basic and translational science to tackle priority areas in controlling the HIV epidemic.
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.
Translating Research Into HIV-related Health Outcomes In The Developing World
Funder
National Health and Medical Research Council
Funding Amount
$714,745.00
Summary
Professor Crowe's research addresses important health issues for HIV infected people living in resource limited countries. Her team validates low cost point of care tests to monitor HIV infection, including a test she co-developed to determine when to start anti-HIV treatment, and investigates how these low cost tests can improve clinical care of people with HIV and TB. In addition she will determine how changes in the immune system increase the risk of heart attacks in young HIV patients.