Novel Epidemiological Methods To Infer The Causal Effects Of Risk Factors On Neuropsychiatric And Cardiovascular Disorders
Funder
National Health and Medical Research Council
Funding Amount
$182,003.00
Summary
Epidemiological studies, which associate risk factors and disease, are central in informing public health policy. Because causality is difficult to ascertain from these associations, public health interventions based on these findings are at some risk of failure. We propose to develop, extend and apply an innovative epidemiological approach, Mendelian randomization (MR) to resolve the causal relationship between risk factors and neuropsychiatric and cardiovascular disorders.
Delineating The Relationship Between Iron And Peroxisomal Disorders: The Role Of The Peroxisomal Enzyme GNPAT In Iron-Overload Disorders
Funder
National Health and Medical Research Council
Funding Amount
$700,767.00
Summary
Hereditary haemochromatosis is one of the most common genetic disorders in humans, affecting 1 in 200 Australians. We have identified a change in a peroxisomal gene which may affect iron levels in humans. The prevalence of this gene change in Australian haemochromatosis patients will be examined followed by a systematic analysis of how this protein controls iron levels in the body. Our goal is to identify and diagnose genetic changes which influence iron loading in haemochromatosis patients.
Histone Demethylase KDM6A Is A Novel Target For Treating Craniosynostosis In Children With Saethre-Chotzen Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$548,854.00
Summary
Children with Saethre-Chotzen syndrome exhibit premature fused coronal sutures, and other skull/ skeletal malformations. Surgical intervention is the only treatment option to ensure optimal cognitive and skeletal development. Our studies have identified a candidate molecular pathway that regulates bone formation by cranial bone cells from these patients. Targeting this key molecular regulator with chemical inhibitors will help prevent the premature fusion of cranial sutures.
Defining The Epigenetic Origins Of Maternally Inherited Disease.
Funder
National Health and Medical Research Council
Funding Amount
$731,162.00
Summary
Epigenetic (non genetic) changes to the DNA in sperm and eggs can alter outcomes in children. Despite the potential for drugs and diet to mediate some of these inherited effects, the processes involved are very poorly understood. By determining the mechanisms that regulate epigenetic inheritance, this project will improve our understanding of how epigenetic mechanisms acting in the parent, can mediate inherited disease and life-long health outcomes in our children.
Characterisation Of Eurl, A Novel Gene Implicated In The Etiology Of Abnormal Brain Development And Intellectual Disability
Funder
National Health and Medical Research Council
Funding Amount
$597,541.00
Summary
Intellectual disability affects around one per cent of Australians, and can arise from genetic abnormalities during fetal life, such as through abnormal regulation of gene expression. We have identified a novel gene, known as eurl, which controls brain assembly as well as the ability of neurons to form functional connections within the brain. We will investigate how this novel gene controls brain development, and characterise eurl as a potential therapeutic target for learning and memory.
Pubertal Transitions In Mental Health And Behaviour: The PHASE-A Study Of Social Roleand Lifestyle Transitions
Funder
National Health and Medical Research Council
Funding Amount
$1,656,785.00
Summary
Over the past four decades problems such as depression, anxiety, self-harm and substance abuse have increased in young people. Recent research indicates that puberty is a time when these problems commonly first emerge. This five-year study of 4000 students will examine a question of whether social transitions that are too soon (e.g. early initiation of sex) or problematic (e.g. bullying from peers) may explain the increase in these health problems as children pass through puberty.
Fear Relapse: Neural Substrates Underlying Its Inhibition And Prevention
Funder
National Health and Medical Research Council
Funding Amount
$437,476.00
Summary
Exposure-based therapies are effective for anxiety disorders such as post traumatic stress, but two challenges remain: 1) patients that have learned to inhibit their fear are likely to relapse, requiring further therapy; 2) many drop out of therapy since it is aversive and anxiety provoking. We use an animal model to: 1) identify the neural substrates underlying fear inhibition; and 2) determine the conditions that prevent relapse and encourage participation in treatment.
The Effect Of Oxytocin On The Formation, Expression And Inhibition Of Fear Memories
Funder
National Health and Medical Research Council
Funding Amount
$390,243.00
Summary
Oxytocin is a hormone peptide which reduces amygdala activation to threatening stimuli and reduces anxiety in people and laboratory rodents. These results suggest that oxytocin could be a valuable pharmacological adjunct to exposure-based therapy for anxiety disorders. However, several questions must be answered before its therapeutic potential can be determined. As such, this project examines the effects of oxytocin on fear-related behaviours in rats, and neural fear circuits in the amygdala.
Deciphering The Role Of Atypical DNA Methylation In Neuronal Genome Regulation And Neurological Disorders
Funder
National Health and Medical Research Council
Funding Amount
$773,484.00
Summary
This research will use a combination of genomic, biochemical and functional genomics approaches to investigate the role of the atypical mCH form of DNA methylation in neuronal genome regulation and function, and provide new insights into the role of the epigenome in healthy brain function and neural pathologies.
Strabismus is the pathological misalignment of the eyes associated with loss of binocular vision and is one of the most common human ophthalmological disorders. Patients with comitant strabismus have full eye movements, whereas patients with incomitant strabismus have limited eye movements, which causes the angle of strabismus to vary with gaze direction. This project aims to define genetic contributors to comitant congenital strabismus.