Chromosomes are structures that carry genes in all our cells. Every human cell has 46 chromosomes. In the nucleus of eukaryotic cells, DNA is highly folded and compacted with specific proteins into a dynamic polymer called chromatin. Gene expression, chromosome division, DNA replication, and repair all act, not on DNA alone, but on this chromatin template. The discovery that enzymes can (re)organise chromatin into accessible and inaccessible configurations revealed mechanisms that considerably e ....Chromosomes are structures that carry genes in all our cells. Every human cell has 46 chromosomes. In the nucleus of eukaryotic cells, DNA is highly folded and compacted with specific proteins into a dynamic polymer called chromatin. Gene expression, chromosome division, DNA replication, and repair all act, not on DNA alone, but on this chromatin template. The discovery that enzymes can (re)organise chromatin into accessible and inaccessible configurations revealed mechanisms that considerably extend the information potential of the genetic code. In addition, it is now established that chromatin structural features can influence gene expression. In vitro studies support a model in which chromatin functions as a barrier for the access to DNA. Therefore this organization has to be tighly regulated and dynamic to allow the protein-DNA interactions critical for nuclear functions. Importantly genome organisation provides in addition to genetic information another layer of information, so called epigenetic, which by definition means that it is stably inherited throughout cellular divisions, yet it is not encoded genetically. Thus each cell type will display a specific epigenome. We have recently constructed small human minichromosomes, which are much easier to study than the much larger normal chromosomes. The present project proposes to define the epigenetic feature across an entire human chromosome using our minichhromosomes as working models. The outcome will be a significant gain in our knowledge on the processes underlying epigenetic regulation, the organisation of specialised chromatin domain, and behaviour of the chromosomes.Read moreRead less
Improving Outcomes For Cancer Patients By Targeting The Epigenome
Funder
National Health and Medical Research Council
Funding Amount
$2,258,892.00
Summary
The most commonly mutated proteins in cancer involve so called epigenetic regulators, a class of proteins that regulate access to our DNA to control gene expression, DNA repair and replication. We and others have recently developed a variety of drugs to help inhibit the aberrant activity of these epigenetic proteins. My research will focus on ways to improve the efficacy of these existing drugs and find new epigenetic therapies to improve the survival of patients with a broad range of cancers.
Improving Interpreting For Dementia Assessments: The MINDSET Study
Funder
National Health and Medical Research Council
Funding Amount
$271,586.00
Summary
The MINDSET Study aims to improve the quality of communication in an interpreter mediated cognitive assessment for dementia. Working with interpreters, clinicians, culturally and linguistically diverse people with dementia, and their carers we will co-design, trial, and implement national online training targeted at interpreters. This training will enable interpreters to be prepared and confident in performing their role impartially, effectively, and accurately.
Circulating Tumour DNA To Monitor Treatment Response And Resistance In Chronic Lymphocytic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$876,950.00
Summary
Many cancers shed small amounts of DNA (ctDNA) into the patient’s bloodstream and recent advances in genomic technologies now allow levels of ctDNA to be accurately measured in the blood. Changes in ctDNA levels have potential to be used as specific markers of disease progression and/or response to cancer therapy. This project will evaluate if ctDNA can be used to monitor treatment responses and individualise treatment decisions in patients with chronic lymphocytic leukaemia.
Investigating Treatments And Biomarkers Of Brain Concussion
Funder
National Health and Medical Research Council
Funding Amount
$428,065.00
Summary
Concussions are a serious and common international health concern, and repeated concussions can have severe long-term consequences on the brain. This project will aim to provide insight into this poorly understood disease projects and ultimately improve the management of concussions in human patients.
National Implementation Trial Of An Evidence-informed Workplace Sitting Reduction Intervention
Funder
National Health and Medical Research Council
Funding Amount
$624,575.00
Summary
Long periods of sitting time are bad for health. We will conduct a three-year national trial with five workplace-health partner organizations testing a website-delivered program for reducing sitting time at work. It will be offered to over 10,000 desk-based employees. We will determine the impacts of the program as well as refinements needed for full-scale dissemination: uptake of the program, how well it can be delivered on a large scale, its impact on sitting time, and the costs involved.
Development Of Vinorelbine As A Tablet Based Therapy To Cure Ectopic Pregnancies
Funder
National Health and Medical Research Council
Funding Amount
$361,594.00
Summary
Ectopic pregnancies occur if the pregnancy implants in the Fallopian tube. They can be deadly and most are treated surgically. We will examine the exciting possibility that instead of surgery, ectopic pregnancies may be cured with a tablet taken just once. We will perform laboratory studies and a clinical trial, giving vinorelbine to women with ectopic pregnancies.
MicroRNA Pathway Control Of Immune Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$631,370.00
Summary
The immune system is comprised of many different cell types, each with a specialised function. Many are short-lived and must be continually replenished throughout life. Abnormalities in this process underlie many human diseases, including immunodeficiency, autoimmunity and cancer. My laboratory seeks to understand the molecular pathways that control development of immune cells and to identify the defects that lead to disease.
Scalability Of The Transform-Us! Program To Promote Children's Physical Activity And Reduce Prolonged Sitting In Victorian Primary Schools
Funder
National Health and Medical Research Council
Funding Amount
$549,823.00
Summary
Transform-Us! is an innovative primary school program that has been found to substantially increase children’s physical activity levels, reduce sitting time and benefit health. With simple changes to the school and classroom environments and teaching practices (eg, standing lessons) we will work with partners in the education and health systems to translate this program across Victorian primary schools to determine the real-world implementation and impact of this program over 5 years.
Centre For Research Excellence In Stroke Rehabilitation And Brain Recovery
Funder
National Health and Medical Research Council
Funding Amount
$2,595,746.00
Summary
The Centre of Research Excellence in Stroke Rehabilitation and Brain Recovery will transform the stroke research and practice landscape in Australia, and accelerate the development of new interventions strongly supported by neuroscience. This unique collaboration will improve patient selection and rehabilitation research methods, create a training culture for the next generation of rehabilitation researchers and effectively implement proven cost effective interventions for Australians.