The Impact Of The Changes In Levels Of Adhesion Molecules NCAM2 And DsCAM On Synapse Formation And Function: Implications For Down Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$334,053.00
Summary
Down syndrome (DS) results from triplication of chromosome 21 and leads to mental retardation, molecular mechanisms of which are not understood. We found that two proteins, NCAM2 and DSCAM, encoded at chromosome 21 are highly expressed in synapses. Synapses are specialized contacts between neurons which allow neurons to process information in the brain. In this project we will test a hypothesis that changes in NCAM2 and DSCAM expression result in synapse abnormalities observed in DS.
How The Dosage Of A Down Syndrome Candidate Gene Affects Neural Circuitry And Behaviour
Funder
National Health and Medical Research Council
Funding Amount
$414,961.00
Summary
In Down syndrome, an extra copy of chromosome 21 increases gene expression and leads to brain defects. We hypothesise that one candidate gene, Dscam2, changes its function with increased expression. This causes brain cells that normally stick to each other to repel each other, leading to inappropriate connections in the brain. We will test this model in the fruit fly and demonstrate for the first time a mechanism dependent on gene expression that can lead to brain abnormalities in Down syndrome.
Identifying Mechanisms That Increase The Pool Of Brain Wiring Proteins
Funder
National Health and Medical Research Council
Funding Amount
$445,093.00
Summary
The computational power of the brain is driven by its interconnected nerve cells. Defects in these connections can lead to neurological disease. This proposal seeks to identify new mechanisms for generating specific connections between nerve cells and thus establishing the proper neural circuitry in a healthy brain.
Elucidation Of The Gene Regulatory Networks That Cause Alzheimer's Disease In Down Syndrome;
Funder
National Health and Medical Research Council
Funding Amount
$782,418.00
Summary
People with Down syndrome have an extra chromosome 21 and all develop Alzheimer's disease. We are able to delete different parts of chromosome 21 in Down syndrome stem cells and turn these cells into the two main cell types of the brain. By comparing the occurrence of Alzheimer disease with gene expression changes in these gene-edited cell types we can identify the gene-regulatory pathways that cause Alzheimer's disease in Down syndrome and identify novel therapeutic targets for sporadic Alzheim ....People with Down syndrome have an extra chromosome 21 and all develop Alzheimer's disease. We are able to delete different parts of chromosome 21 in Down syndrome stem cells and turn these cells into the two main cell types of the brain. By comparing the occurrence of Alzheimer disease with gene expression changes in these gene-edited cell types we can identify the gene-regulatory pathways that cause Alzheimer's disease in Down syndrome and identify novel therapeutic targets for sporadic Alzheimer's disease.Read moreRead less
A COMMUNITY BASED STRENGTH TRAINING PROGRAM TO IMPROVE WORK TASK PERFORMANCE IN YOUNG ADULTS WITH DOWN SYNDROME
Funder
National Health and Medical Research Council
Funding Amount
$180,649.00
Summary
This study will compare the outcomes of a 10 week twice a week community-based weight training program for young adults with Down syndrome with an art program. It will establish if a student-led exercise program can improve their performance of work tasks and their activity levels. Should the program prove beneficial, we aim to achieve the long-term outcome of exercise being implemented as a sustainable, inclusive recreation option for this group.
Improving Breathing Support For Newborn Infants In Non-Tertiary Centres: The HUNTER Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,203,844.00
Summary
Every year in Australia, thousands of newborn babies have breathing difficulties. Our trial will study a new, simple method of providing breathing support to newborn babies in special care nurseries, called high-flow (HF). HF is cheaper, easier to use, and more comfortable for babies than the current standard treatment, called CPAP. If HF is as good as CPAP at supporting babies' breathing, it will change practice in Australia and around the world.
Epigenetic Regulation Of L1 Retrotransposition In Mouse Models Of Abnormal Human Neurobiology
Funder
National Health and Medical Research Council
Funding Amount
$417,812.00
Summary
Retrotransposons are mobile genes that copy-and-paste themselves to spread in DNA. Until very recently, they were thought to only be active in sperm and egg. In our recent work, we demonstrated that they also move in the brain. In the current study, we will use cutting-edge technologies to determine how retrotransposons change the genetic makeup of neurons in neurodevelopmentally impaired mice to predict whether these mutations would also be present in human brain disorders.
Antiphospholipid Syndrome Related Thrombosis: Understanding The Disease Pathogenic Mechanisms Is The Key To Better Diagnosis And Treatment
Funder
National Health and Medical Research Council
Funding Amount
$607,497.00
Summary
Patients with the Antiphospholipid Syndrome develop thrombosis at a young age. It requires long-term treatment with blood thinning medications, which have risks of severe bleeding. Methods are needed to decide which patients require long term treatment, avoiding unnecessary treatment in low risk patients. Such methods do not currently exist. In this study we explore how useful two novel assays developed by us are in identifying which of these patients are at high risk of thrombosis.
Overcoming Barriers To Improved Physical Health In People With Severe Mental Illness
Funder
National Health and Medical Research Council
Funding Amount
$864,658.00
Summary
People with severe mental illness have high rates of cardiometabolic disease and reduced life-expectancy. Public intervention campaigns have had little impact on component risks (obesity, smoking, physical inactivity, poor nutrition). This study will determine factors associated with changes in cardiometabolic profiles in people with severe mental illness; examine impediments to risk modification; and develop targeted interventions for implementation within mental health services.
HIV is a rapidly evolving virus, and within an infected individual it continually acquires new mutations and joins together mutations by recombination. We have developed a novel system for studying recombination, and find that different individuals have different recombination rates, which may contribute to why some individuals survive longer. This project aims to identify the mechanisms responsible for differing recombination rates and how we can alter these to improve patient outcome.