Targeting Inflammatory Skin Disease Using An Immune-modulatory Human Signal Peptide
Funder
National Health and Medical Research Council
Funding Amount
$698,836.00
Summary
Effective drugs are desperately needed for the improved treatment of inflammatory diseases. We will determine how a modified human peptide, which we have discovered and can make, works to suppress harmful skin inflammation. We will design new formulations to deliver our drug to the skin in order to better treat psoriasis, an autoinflammatory skin disease. We will also trial our new drug in models of atopic dermatitis a debilitating skin disease for which there is limited treatment options.
Understanding The Innate Immune Response To Viral Infection Of The Female Reproductive Tract And Placenta
Funder
National Health and Medical Research Council
Funding Amount
$784,273.00
Summary
Viral infection of the female reproductive tract (FRT) can have a significant impact on FRT health and may cause significant birth defects if the virus infects the placenta and developing fetus. In this application we will investigate the role of a novel molecule termed interferon epsilon and how it impacts viral infection of the FRT, the fetus and how the placenta responds to viral infection. This work will develop innovative antiviral strategies to combat viral infections of the FRT.
Exploiting Anti-capsid Humoral Immunity Induced In Infants Receiving Gene Therapy For Spinal Muscular Atrophy To Engineer The Next Generation Of Gene Transfer Vectors
Funder
National Health and Medical Research Council
Funding Amount
$1,105,993.00
Summary
After 25 years of incremental progress the possibility of treating genetic disease by gene therapy has become a therapeutic reality. This has been achieved by harnessing the gene transfer power of viruses made harmless by genetic engineering. A major limitation is that up to 50% of patients are currently excluded by pre-existing immunity to these powerful tools. Using 'evolution in a dish', we will engineer a new generation of these tools capable of bypassing pre-existing immunity by stealth.
THE IMMUNOLOGICAL LEGACY OF OBESITY ON VIRAL PATHOGENESIS
Funder
National Health and Medical Research Council
Funding Amount
$652,275.00
Summary
Obesity is a key risk factor for severe viral infections. Our preliminary data suggest that in mice this susceptibility is not reduced by weight loss. In this grant we will investigate a) the mechanisms driving the legacy effect of obesity on antiviral immunity b) whether or not we can reverse this legacy effect by treatment with the drug MCC950 and c) the antiviral response of overweight children and adults who have and haven't recently lost weight.
Developing New Immunotherapeutics Through Studying Immune Effectors In Situ
Funder
National Health and Medical Research Council
Funding Amount
$1,369,054.00
Summary
The immune system deploys pore forming proteins to clear viral and bacterial infections and to eliminate cancerous cells. The unwanted activities of these molecules, however, results in chronic disease and in transplant rejection. We aim to understand how pore forming immune weapons interact with our own cells, with the goal of using this information to develop new approaches to treat immune driven disease and to improve the success of transplantation therapy.
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.
Developing An In Vitro Model Of A Human Blastocyst
Funder
National Health and Medical Research Council
Funding Amount
$890,062.00
Summary
Using novel cellular and molecular technologies we propose to develop an artificial model of an early human blastocyst. This will allow us to study the first initial steps in human development without the use of real embryos. Such a model will not only help us decipher the first steps in human development, but we anticipate it will be essential to study how gene mutations and the environment affect this initial step in human development.
Vaccine To Prevent Influenza Virus And Bacterial Super-infection.
Funder
National Health and Medical Research Council
Funding Amount
$707,717.00
Summary
Influenza viruses have the ability to pre-dispose infected hosts toward secondary bacterial complications. The mortality of viral infections that are complicated by a concurrent, or subsequent, bacterial infection (known as a super-infection), is often greater than that of either the virus or the bacteria alone. We will develop a novel multi-pathogen vaccine candidate against the major upper respiratory tract pathogens - Influenza A and Streptococcus pyogenes to prevent super-infections.
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.
Relaxin Receptor Structural Determination To Aid Therapeutic Development
Funder
National Health and Medical Research Council
Funding Amount
$1,249,114.00
Summary
The receptor for the peptide hormone relaxin, RXFP1, is being targeted by numerous drug companies for the treatment of cardiovascular disease. However, the lack of molecular detail of how relaxin binds and activates RXFP1 is hindering new drug development. We will determine the structure of the complex of relaxin bound to RXFP1 and the mechanism by which this activates cells. The knowledge gained will aid in the design of new drugs targeting RXFP1 for the treatment of cardiovascular disease.