Characterisation Of Anti-HBs Responses In Patients Undergoing Functional Hepatitis B Cure: Implication For Future Therapies
Funder
National Health and Medical Research Council
Funding Amount
$723,649.00
Summary
The hepatitis B virus causes liver cirrhosis and liver cancer. There is no cure for hepatitis B. However, a small number of patients can naturally rid themselves of the virus. We have identified 14 of these individuals and discovered that they have a unique immune response that is responsible for these “natural” cures. We plan to characterise this immune response and turn it into a therapeutic vaccine which can be used to cure patients who are still chronically infected.
Investigating The Host Determinants Of Viral Clearance Versus Collateral Pathology In Chronic Infection
Funder
National Health and Medical Research Council
Funding Amount
$1,250,756.00
Summary
Hepatitis B virus has infected over 2 billion people. Some people control the virus but it remains incurable and there is a lifelong risk of liver cancer. Understanding how host cells interact with the virus, the mechanisms the cells use in an attempt to eliminate the virus and the mechanisms the virus uses to sabotage these responses, will provide insights that could lead to therapies. Potential therapies could be applicable to other infections like HIV-1 and tuberculosis.
Determinants Of Sustained Virological Response After Discontinuation Of Long-term Nucleoside Analogue Therapy In Chronic Hepatitis B Patients
Funder
National Health and Medical Research Council
Funding Amount
$976,778.00
Summary
Guidelines currently recommend lifelong treatment for patients with chronic hepatitis B, with associated cost and risks of drug resistance and side effects. It has recently been suggested that up to 50% of patients may safely and successfully stop drug after long-term treatment. Our project will identify which patients can safely stop treatment, by performing detailed studies of the human immune system and the hepatitis B virus. This will be an important advance for patient care.
How Do Cross-reactive Memory B Cells Affect Influenza Vaccine Titers?
Funder
National Health and Medical Research Council
Funding Amount
$798,049.00
Summary
Influenza vaccines are updated frequently to protect against the highly variable influenza virus. Despite careful selection of vaccine viruses, most influenza vaccines provide only modest protection and protection is poor some years. In turn, the response to vaccination varies between individuals. This probably reflects complex and variable histories of influenza infection and vaccination. The project investigates how past influenza exposure influences vaccine responses and effectiveness.
New Drug Combinations To Enhance Elimination Of Hepatitis B Infection
Funder
National Health and Medical Research Council
Funding Amount
$888,304.00
Summary
We have developed a therapy that kills hepatitis B virus infected cells and promotes elimination of infection. We are now testing novel drugs that can be used to maximise the efficacy of our new treatment to promote better outcomes that may be translated to other infections.
Targeting RCAN1 To Treat Type 2 Diabetes And Obesity
Funder
National Health and Medical Research Council
Funding Amount
$814,468.00
Summary
Obesity and impaired insulin secretion are significant contributors to Type 2 diabetes. In this project we demonstrate that a protein called RCAN1 contributes to both fat mass and insulin secretion and that this contribution is exacerbated in obesity and in Type 2 diabetes. We will identify how RCAN1 controls these major metabolic pathways with outcomes including the development of new therapeutics for obesity and Type 2 diabetes.
Long Term Persistence Of HIV In The Liver And The Clinical Impact On HIV-HBV Co-infection
Funder
National Health and Medical Research Council
Funding Amount
$1,393,245.00
Summary
This grant will address a major question in HIV cure research - the role of the liver as an HIV reservoir and the impact of HIV persistence in HIV-infected patients on suppressive antiretroviral therapy (ART) on liver disease, in the setting of HIV-HBV co-infection. We will trial a novel intervention to reduce HIV infection of the liver that could potentially reduce chronic liver disease in this setting.
Brain Protection: A new therapeutic approach for Multiple Sclerosis In Multiple Sclerosis (MS), the immune system mistakenly attacks the brain. The immune attacks destroy myelin, the protective coat around electrical cables in the brain (demyelination). Current treatments for MS are only partially effective, and work by reducing the number and severity of these attacks. However, MS-related permanent disability in the majority of sufferers is due to the development of progressive MS, and current ....Brain Protection: A new therapeutic approach for Multiple Sclerosis In Multiple Sclerosis (MS), the immune system mistakenly attacks the brain. The immune attacks destroy myelin, the protective coat around electrical cables in the brain (demyelination). Current treatments for MS are only partially effective, and work by reducing the number and severity of these attacks. However, MS-related permanent disability in the majority of sufferers is due to the development of progressive MS, and current therapies do not reduce this progression. It is believed that one major cause of this permanent disability is permanent myelin loss. Interestingly, we have already shown that the growth factor LIF is made by the body during MS-like inflammation, and that it limits damage by directly protecting myelin-producing cells. However, the bodies own LIF production during inflammation is sub-maximal, because myelin protection can be enhanced by giving additional therapeutic LIF. This suggests that (1) The brain produces a defence response to harmful inflammation and that (2) This defence response can be enhanced therapeutically. We therefore want to define exactly how LIF enhances myelin survival. We have measured the response to LIF in myelin-producing cells, and have discovered that it strongly stimulates the production of the small protein galanin. We will now assess if galanin itself protects myelin and myelin-producing cells, and we will test this both in isolated cells and whole animal models. If galanin production is a major mechanism by which the body tries to limit the damage from abnormal inflammation during MS, then medications that mimic the action of galanin (which are already under development for different reasons) could become a major new therapy for Multiple Sclerosis.Read moreRead less
Cytokine Signalling And Insulin Resistance In Obesity.
Funder
National Health and Medical Research Council
Funding Amount
$512,065.00
Summary
Western communities are experiencing an epidemic of obesity that is contributing to diabetes, heart disease, and premature death. This project is investigating why being overweight and obese causes diabetes. Improved understanding about how hormones regulates the body's storage and breakdown of fat and responsiveness to insulin will enable the development of new medicines for the treatment of obesity and the prevention of diabetes.