Organisation Of The Genome During The Development Of Antibody-secreting Cells
Funder
National Health and Medical Research Council
Funding Amount
$886,155.00
Summary
Each cell of our body contains over two metres of DNA that must be correctly packaged in order for our cells to function. We are using cutting-edge molecular biology techniques to study how this DNA circuitry is established in the white blood cells of our immune system that produce antibodies. Our novel approaches will reveal unique strategies to modulate immune responses to our benefit.
Determining The Molecular Basis Of Therapy Resistance Conferred By Genetic Lesions In The Tumour Protein TP53 In Haematological Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$885,183.00
Summary
Blood cancers that have genetic lesions in a tumour suppressor protein called TP53 respond poorly to therapy. Curing these patients is extremely challenging and new therapeutic strategies are desperately needed. Here, we aim to uncover the molecular mechanisms of drug resistance caused by loss of TP53 function and rationally design new therapies that may be curative. To do this, our team of leading scientists and clinicians will study patient samples and pre-clinical models of blood cancer.
Reprogramming Human Fibroblasts Into Induced Trophoblast Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$889,064.00
Summary
We have been able to generate artificial human trophectoderm which is the tissue that creates the placenta. This will allow us to do research in how the genes control the fate of these cells without the need of human embryos or placenta. We anticipate that the derivation and characterising these cells will revolutionise placenta research, which in turn will contribute to the establishment of new therapies for placenta disease and infertility.
Growth Factor Directed Developmental And Pathological Lymphangiogenesis
Funder
National Health and Medical Research Council
Funding Amount
$1,048,507.00
Summary
The formation of new lymphatic vessels occurs in normal development and in diseased tissues in cancer and cardiovascular disease. We have developed an understanding of how lymphatics form in development but we understand far less about how they form in disease. This project will apply multidisciplinary approaches, including genetics and computational biology, to compare how lymphatics form in development and disease. We hope to uncover new ways to manipulate this process for therapeutic gain.
Bring Out Your Dead - How Does Defective Apoptotic Cell Clearance By Tingible Body Macrophages Lead To The Activation Of Self-reactive B Cells In SLE?
Funder
National Health and Medical Research Council
Funding Amount
$721,597.00
Summary
Good housekeeping is critical to the day-to-day running of the immune system. In the case of the germinal centre, a key structure where plasma cells are generated, the ability to clear away dead and dying cells is critical because failure to do so can lead to the spillover of cellular waste and debris into the follicle where they can activate harmful B cells to make autoantibodies and cause disease. Understanding how this happens can lead to new ways to target and treat autoimmune diseases.
Using Immunological Principles To Inform Malaria Vaccine Design
Funder
National Health and Medical Research Council
Funding Amount
$577,763.00
Summary
Malaria kills ~420,000 people each year worldwide. While a vaccine does exist, efficacy is poor and protection wanes rapidly. We have made breakthroughs in understanding the immune response to malaria that allow us to design a new generation of malaria vaccines. Based on this we aim to generate a vaccine that induces sustained levels of high-quality antibodies targeting multiple targets on the parasite and so can provide sustained long-term protection.
Molecular Dissection Of Allergen Sensitisation And Immunotherapy: Direct Application To Precision Medicine In Treatment Of Asthma
Funder
National Health and Medical Research Council
Funding Amount
$1,270,097.00
Summary
Asthma is a major global health burden with huge socioeconomic impact. Most asthmatic patients are allergic. Allergen immunotherapy is the only treatment to alter the natural disease course, but does not work in many treated patients, and robust laboratory biomarkers for patient selection and immune monitoring of treatment success are lacking. Therefore, allergen immunotherapy is not offered to most patients who then rely on medications indefinitely. This research will address these needs.
Identifying An Autism Gene Network Governing Stem Cell Division, Neurogenesis And Cortical Malformation
Funder
National Health and Medical Research Council
Funding Amount
$1,003,589.00
Summary
Failure to produce neural stem cells and new neurons in the embryonic cortex results in cortical malformations and autism, and thus has profound consequences for the individual's survival and quality of life. Here we explore how a unique network of autism proteins maintains stem cell activity and neuronal production, thereby ensuring the fidelity of cortical development.
Hepatitis B is a leading cause of cirrhosis and liver cancer. Treatments for hepatitis B control the virus, but do not cure it, so people stay on treatment for many years. We have identified an exciting new treatment approach by targeting a gene that controls liver metabolism, called TM6SF2. We will target this gene to develop a cure for hepatitis B.
Molecular Regulators Of Adaptive Immunity To Overwhelming Viral Infections
Funder
National Health and Medical Research Council
Funding Amount
$786,898.00
Summary
Diseases caused by overwhelming viral infections, such as COVID-19, are associated with widespread impairments in immunity and constitute a major burden to human health. We have discovered that the molecule c-Myb is essential for the maintenance of immunity during chronic infection. In order to lay the foundations for novel and innovative anti-viral therapies, this project will dissect the molecular pathways regulated by c-Myb that maintain immunity during severe or chronic infection.