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
A Vulvar Cancer Cluster In Young Indigenous Women In Arnhem Land: Investigation Of Community Knowledge, Genetic Susceptibility And Supportive Care Response
Funder
National Health and Medical Research Council
Funding Amount
$711,841.00
Summary
Cancer of the vulva is 50 times more common in young Aboriginal women in Arnhem Land than in other women. Human Papillomavirus (HPV), which also causes cervical cancer, is the usual cause of this cancer; initial investigations have found that HPV is present in these cancers but is not the reason for the excessive incidence. This study will investigate local knowledge about this disease, and whether inherited susceptibility or an environmental cancer-causing substance are the cause of the excess.
FANC Gene Mutations In Acute Myeloid Leukaemia Biology And Treatment
Funder
National Health and Medical Research Council
Funding Amount
$900,780.00
Summary
We have found mutations in DNA repair genes in AML patients, and associated the presence of these with increased risk of developing AML. Our hypothesis is that the presence of these mutations leads to reduced efficiency of DNA repair, and increased risk of additional mutations and leukaemic transformation. Our aim is therefore to determine the changes associated with these mutations in blood cell precursors, and to investigate the potential of targeted therapies for this group of patients.
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
Major Histocompatibility Complex (MHC) Genetics Of Ankylosing Spondylitis
Funder
National Health and Medical Research Council
Funding Amount
$568,612.00
Summary
Ankylosing spondylitis (AS) is the prototypic condition of a group of types of inflammatory arthritis called 'seronegative spondyloarthropathies'. These conditions are the most common form of inflammatory arthritis in white populations and occur worldwide. One third of the risk of developing AS is determined by genes within a region called the 'major histocompatibility complex' (MHC), in addition to the gene HLA-B27, the main gene causing AS. We aim to identify the remaining MHC genes.
The Immunogenetics Of Ankylosing Spondylitis: A Genetic And Functional Investigation Of IL23R And Related Genes
Funder
National Health and Medical Research Council
Funding Amount
$536,679.00
Summary
Ankylosing spondylitis (AS) is a common inflammatory arthritis which causes primarily back pain and stiffness, and affects 1-250 individuals. Our group identified association between tagging genetic markers in the gene IL23R and AS, and our preliminary data suggests some related genes are involved as well. This study aims to identify the key genetic variants involved and determine the mechanism by which they cause AS.
There is a need to improve early detection, monitoring of relapse, and treatments for melanoma, to increase long-term survival. My research vision is to use innovative and cutting edge approaches to conduct a range of complementary studies under three broad but inter-related themes: Theme 1 – Genetic predisposition to melanoma in the general population; Theme 2 – Genetic predisposition to melanoma in high-density families; Theme 3 – Somatic aberrations underlying melanoma development.
The Role Of Insulin Hypersecretion In Beta Cell Dysfunction In Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$318,622.00
Summary
The treatment of diabetes involves the use of drugs that stimulate the release of insulin from the pancreas to reduce the high blood sugar levels. However, we believe that while in the short term this is a good strategy, in the long-term it damages the cells that produce insulin leading to a worsening state of diabetes. It is the aim of this application to understand the mechanisms by which the insulin producing cells are damaged when forced to oversecrete insulin.
Leukaemia, the most common form of childhood cancer, constitutes an important component of Australia's overall cancer burden. We aim to improve our understanding of the genetic and familial contributions to this disease. By establishing the Victorian Paediatric Family Cancer Study, we have evidence of a relationship between maternal age, onset of leukaema and overall risk of cancer in the family. We aim to determine if this finding is genetically based, implying a larger inherited component than ....Leukaemia, the most common form of childhood cancer, constitutes an important component of Australia's overall cancer burden. We aim to improve our understanding of the genetic and familial contributions to this disease. By establishing the Victorian Paediatric Family Cancer Study, we have evidence of a relationship between maternal age, onset of leukaema and overall risk of cancer in the family. We aim to determine if this finding is genetically based, implying a larger inherited component than previously recognized.Read moreRead less
A Genome Wide Association Study For Alcohol And Nicotine Addiction Susceptibility Genes
Funder
National Health and Medical Research Council
Funding Amount
$872,816.00
Summary
Alcohol and nicotine addiction are major public health problems within Australia. As well as the personal and economic costs associated with dependence, there is a wide range of downstream health effects from heavy drinking and smoking. This is a proposal for a genome wide association study to systematically screen and identify genetic variants within the Australian population that affects an individual's liability to developing alcohol addiction, nicotine addiction or both.