Gene Therapy For The Treatment Of Retinal Dystrophy In The RPE65 Knockout Mouse Using RAAV Virus Mediated Gene Therapy.
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
RPE65 is a gene that is found exclusively within the retina. At the moment the exact role of RPE65 is not known, however recent research has shown that mutations in the RPE65 gene have been found in a number of inherited retinal dystrophies (these dystrophies include Leber congenital amaurosis and autosomal recessive retinitis pigmentosa). It therefore appears that a functional, non-mutated RPE65 gene is essential for normal vision. A mouse model of RPE65-related retinal dystrophies has been rec ....RPE65 is a gene that is found exclusively within the retina. At the moment the exact role of RPE65 is not known, however recent research has shown that mutations in the RPE65 gene have been found in a number of inherited retinal dystrophies (these dystrophies include Leber congenital amaurosis and autosomal recessive retinitis pigmentosa). It therefore appears that a functional, non-mutated RPE65 gene is essential for normal vision. A mouse model of RPE65-related retinal dystrophies has been recently developed, by producing a RPE65 knockout mouse breed in which the mouse's RPE65 gene has been mutated into an inactive form. Research on these mice have shown that they develop retinal dystrophies very similar to those seen in patients with mutated RPE65 genes. We propose to use these RPE65 knockout mice to test potential methods for treating the RPE65-related retinal dystrophies in patients. In particular, we will study the potential of using gene therapy to treat these diseases. The project will involve delivering a new, functional RPE65 gene to the retinas of the RPE65 knockout mice. The new, functional RPE65 gene will then replace the inactive, mutated RPE65 gene within the mouse retinas, an action that we predict will be able to stop these mice developing retinal dystrophy. Performing such a study will allow us to improve our understanding of the RPE65-related retinal dystrophies, and provide an indication of whether they can be treated with gene therapy.Read moreRead less
Resolving Human Immunodeficiency Virus (HIV) Transmission
Funder
National Health and Medical Research Council
Funding Amount
$745,213.00
Summary
To increase the breadth of HIV prevention strategies, it is imperative that we biologically understand how HIV enters our bodies. Through two unique clinical cohorts, we will determine why circumcision is protective and how a commonly acquired sexual transmitted infection (human papilloma virus) can increase HIV transmission.
Intrinsic Host Antiviral Activity Against Pathogenic Filoviruses
Funder
National Health and Medical Research Council
Funding Amount
$488,754.00
Summary
Bats are a major reservoir for deadly human viruses including Ebola and Marburg virus. In contrast to humans, bats can be infected with these viruses without showing clinical signs of disease. The reason why bats can co-exist with these viruses is unknown. This study will determine if a bat antiviral molecule contributes to limiting virus release compared to the human version that could reveal strategies to prevent and control these deadly viruses in humans.
Identification Of Host Factors That Restrict Influenza Virus Replication In Macrophages
Funder
National Health and Medical Research Council
Funding Amount
$566,446.00
Summary
Influenza virus infects different cells in the airways, including immune cells (macrophages) and non-immune cells (epithelial cells). Epithelial cell infection results in virus amplification and release whereas macrophage infection leads to virus destruction. This project will identify cellular factors expressed by macrophages that block virus amplification and release. Identification of novel antiviral factors is an important step towards developing strategies to reduce influenza disease.
Identification Of Host Restriction Factors That Block Respiratory Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$956,898.00
Summary
Following inhalation, respiratory viruses can infect and grow in airway epithelial cells. Although immune cells such as macrophages are also susceptible to infection, this is generally abortive and new viruses are not released. This project will identify proteins induced in macrophages that block respiratory viruses and prevent their spread in the airways. We will also define mechanisms by which some virulent strains overcome this block to grow in macrophages.
The Role Of Varicella Zoster Virus In Modulating Cutaneous Infection
Funder
National Health and Medical Research Council
Funding Amount
$555,892.00
Summary
Varicella zoster virus (VZV) causes two skin diseases: chickenpox and shingles. VZV can causes significant morbidity in children and adults and life-threatening disease in immunocompromised people. This project aims to improve our understanding of how VZV affects the function of specialised skin cells to provide information for the development of a better vaccine to lessen the impact of VZV disease on the community.
Pandemic Influenza Vaccine: Exploiting The Conserved HA Cleavage Site
Funder
National Health and Medical Research Council
Funding Amount
$243,300.00
Summary
Influenza virus needs to cleave its surface spike protein, hemagglutinin or HA, to become mature and infectious. This project is aimed at producing a vaccine that will block the cleavage thus rendering the virus non-infectious. To achieve this, we will use synthetic fragments (called peptides) of the viral HA spike protein mimicking its cleavage site to immunize mice. This will produce specific antibodies that will bind to the cleavage site while the virus is inside the infected cell, thus preve ....Influenza virus needs to cleave its surface spike protein, hemagglutinin or HA, to become mature and infectious. This project is aimed at producing a vaccine that will block the cleavage thus rendering the virus non-infectious. To achieve this, we will use synthetic fragments (called peptides) of the viral HA spike protein mimicking its cleavage site to immunize mice. This will produce specific antibodies that will bind to the cleavage site while the virus is inside the infected cell, thus preventing the viral spike protein from being cleaved and remain immature. This idea is particularly suited to fight the bird flu, as all pathogenic bird influenza viruses cleave HA spike proteins within the infected cell.Read moreRead less