Hemoglobin is the major protein in red blood cells and is essential for the transport of oxygen from the lungs to the tissues. The disorders of hemoglobin production are the commonest genetic diseases world-wide. These diseases can be markedly improved with elevation of the form of hemoglobin produced by the developing fetus, fetal hemoglobin. We have identified a key factor important for fetal gene expression. We will now determine whether manipulation of this factor can cure hemoglobin disorde ....Hemoglobin is the major protein in red blood cells and is essential for the transport of oxygen from the lungs to the tissues. The disorders of hemoglobin production are the commonest genetic diseases world-wide. These diseases can be markedly improved with elevation of the form of hemoglobin produced by the developing fetus, fetal hemoglobin. We have identified a key factor important for fetal gene expression. We will now determine whether manipulation of this factor can cure hemoglobin disorders.Read moreRead less
A Novel Genetic Element Controlling Adult Hemoglobin Production
Funder
National Health and Medical Research Council
Funding Amount
$493,907.00
Summary
Disorders of the blood protein hemoglobin are the commonest genetic diseases worldwide, and include thalassemia and sickle cell disease. In this proposal we study two novel mouse lines that exhibit thalassemia, but lack any of the known genetic mutations that cause this disease. These mice afford us the opportunity to make unique observations into how hemoglobin is produced, and thereby provide a platform for new therapeutic approaches in these devastating diseases of the blood.
Sickle cell anaemia and ?-thalassaemia are debilitating diseases for which there is no effective treatment. Patients require lifetime blood transfusions and drugs with significant side effects. These diseases are ameliorated in patients that express foetal haemoglobin into adulthood. The goal of this research is to understand how foetal haemoglobin is normally turned off at birth. This will ultimately help us discover how to switch it back on to treat patients.
The Role Of UPF3B And Nonsense Mediated MRNA Decay Surveillance In The Pathology Of Intellectual Disability.
Funder
National Health and Medical Research Council
Funding Amount
$789,954.00
Summary
Proper functioning of the nonsense mediated mRNA decay (NMD or 'mRNA police') is crucial for any cell to ensure normal development and function. When NMD is compromised the outcome is learning and memory problems, autism or schizophrenia. Under this project we study malfunctioning NMD using stem and neuronal cells derived from patients' skin cells. Some of the affected genes might be considered for therapeutic interventions. NMD is relevant to 1000s of human disorders and as such it is of fundam ....Proper functioning of the nonsense mediated mRNA decay (NMD or 'mRNA police') is crucial for any cell to ensure normal development and function. When NMD is compromised the outcome is learning and memory problems, autism or schizophrenia. Under this project we study malfunctioning NMD using stem and neuronal cells derived from patients' skin cells. Some of the affected genes might be considered for therapeutic interventions. NMD is relevant to 1000s of human disorders and as such it is of fundamental importance.Read moreRead less
Uncovering New Epigenetic-based Regulatory Mechanisms Of Gene Expression: Novel Links Between Histone Variants, RNA Function And Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,053,671.00
Summary
It is estimated that greater than 90% of human genes undergo alternative RNA splicing, which can explain how protein diversity is achieved with a limited number of genes. However, how alternative splicing patterns are established remains poorly understood but is an important question given that 15-50% of human disease mutations are associated with changes to the splicing patterns of RNA. We have uncovered a new splicing mechanism, which involves changing the way DNA is packaged in a cell.
Molecular Control Of Interneuron Development And Function In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$527,828.00
Summary
This project will study the changes that occur in neurons, during normal brain maturation and in pathology. We hypothesise that early signs of brain malfunction can be detected in neurons before symptoms appear. The role of a gene will be studied during development and disease in a mouse model of autism, in order to identify the molecular and electrical signs of abnormal activity. This research will ultimately enable us to propose new strategies to treat symptoms of brain disease.
Identifying Cell Type Specific Biomarkers Of Recurrent Oral Squamous Cell Carcinoma And Mapping Cancer-stroma Interactions Using Single Cell Biology And Cell-to-cell Communication Networks
Funder
National Health and Medical Research Council
Funding Amount
$892,858.00
Summary
Cancer is a major cause of death in Australia. Despite advances in our understanding of the mutations that occur and the sets of genes expressed in cancer we have a major gap in our understanding of what is happening within tumours. Using new single cell technology we will generate new molecular portraits of cancers that give us understanding of the sets of genes expressed on individual cancer cells, the normal cells within a tumour and how they interact with cancer cells to form a tumour.
Investigating A Novel Genetic Regulator Of Cardiac Rhythm
Funder
National Health and Medical Research Council
Funding Amount
$557,101.00
Summary
Cardiac arrhythmias affect approximately 5% of the population and have a high association with sudden death. Whilst the cause of cardiac arrhythmia is complex, we know that genetic mutations play a role however we don't know all the genes important for cardiac rhythm. It is imperative that we identify all the genes in this process, so we can determine which mutations cause arrhythmia. We have identified a new gene that causes cardiac arrhythmia and seek to understand how it functions.
The FIELD trial, one of the largest type 2 diabetes studies world-wide, involving 9795 people over five years, demonstrated that the blood fat lowering drug fenofibrate protects against diabetic eye, kidney and nerve damage and some cardiovascular events. The FIELD NOMAD Study will identify novel molecular and biochemical markers of diabetes complications and treatment response in at least 1000 subjects with diabetes. Results are expected to improve diabetes care and develop new treatments.
Integrating Immunity And Genetics In Follicular Lymphoma To Establish A Prognostic Score Fit For The Modern Era
Funder
National Health and Medical Research Council
Funding Amount
$1,377,174.00
Summary
Follicular lymphoma (FL) is divided into early and advanced stages. Early stage FL is frequently cured, but there is no way to identify who will be cured and who won't. By contrast advanced stage FL is incurable. Our unique access to well-annotated clinical trial and population based cohorts allows us to perform a detailed biological comparison of early and advanced FL, to gain a deeper understanding of the impediments to eradicating the disease, and to predict outcome to conventional therapy.