A NOVEL MOUSE MODEL TO INVESTIGATE THE MECHANISMS OF VIRUS-INDUCED ARTHRITIS
Funder
National Health and Medical Research Council
Funding Amount
$336,000.00
Summary
We have developed a novel animal model by which to study arthritic disease caused by insect-transmitted viruses known as arboviruses. The existence of this model and novel reagents provides an excellent opportunity to further explore the basic mechanisms of infectious disease in a complete functioning animal, rather than specific cultured cells. The study will use modern approaches in molecular and cellular biology to achieve this goal. The production by our immune systems of soluble mediators ( ....We have developed a novel animal model by which to study arthritic disease caused by insect-transmitted viruses known as arboviruses. The existence of this model and novel reagents provides an excellent opportunity to further explore the basic mechanisms of infectious disease in a complete functioning animal, rather than specific cultured cells. The study will use modern approaches in molecular and cellular biology to achieve this goal. The production by our immune systems of soluble mediators (cytokines-chemokines) and antibodies is an overwhelming positive aspect of our physiological response to infection by microbes. Protection from disease by these immune compounds can happen naturally, or the body's ability to produce these factors can be exploited to our benefit via the administration of vaccines. However, these factors can also be detrimental to the host contributing to severe disease. For instance, work performed almost 40 years ago showed for the first time that under particular conditions, antibodies against viruses can enhance infection, instead of inhibiting infection as normally seen. In the intervening years work by scientists all over the world has associated antibody-dependent enhancement (ADE) of infection to many types of viruses; ADE is even thought to be a risk factor to serious disease with dengue virus, and has been shown in vitro for the AIDS virus and Ebola virus. We have recently discovered a molecular mechanism which explains how antibody enhances viral infection in vitro. In studies on immune cells infected with Ross River Virus (RRV) we found that infection helped by antibody resulted in the specific disruption to the production of cellular chemicals which are toxic to viruses. Are these mechanisms of antibody-enhanced infection also found in animals? Will such mode of infection cause enhanced disease and tissue pathology (arthritis) in animals?Read moreRead less
The Interplay Between Viperin, Peroxisomes And The Cellular Innate Antiviral Response
Funder
National Health and Medical Research Council
Funding Amount
$556,127.00
Summary
Infection with a virus initiates a cellular antiviral response that attempts to limit viral replication, however how this response is regulated is not well understood. In this proposal we will investigate a cellular protein (viperin) that can regulate this process by interaction with peroxisomes to amplify the antiviral response. This work will provide possible targets for therapeutic manipulation of the innate immune response that will be applicable to a wide range of viral infections.
Improving Pain And Movement Outcomes In Symptomatic Knee Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
People fear getting painful knee osteoarthritis (OA) more than any other disease – it is seen as progressive and incurable. It often stops people from moving and staying healthy, resulting in an enormous burden on sufferers and the health care system. This program of research aims to understand what brain & nervous system processes might underlie these pain and movement problems and whether new brain-targeting treatment helps. This will allow us to better match treatment to what patients need.
Imaging The Hepatitis C Virus Life Cycle In Real-time
Funder
National Health and Medical Research Council
Funding Amount
$477,504.00
Summary
Hepatitis C virus (HCV) is a serious viral pathogen that causes significant liver disease. This proposal plans to examine how two proteins from the HCV, core and NS5A, interact with host proteins and pathways to facilitate viral replication and release of HCV; two processes that are poorly understood. Specifically we will tag viral proteins to allow us to investigate the HCV life cycle in living cells and determine the role of core and NS5A in facilitating HCV replication. This proposal may unco ....Hepatitis C virus (HCV) is a serious viral pathogen that causes significant liver disease. This proposal plans to examine how two proteins from the HCV, core and NS5A, interact with host proteins and pathways to facilitate viral replication and release of HCV; two processes that are poorly understood. Specifically we will tag viral proteins to allow us to investigate the HCV life cycle in living cells and determine the role of core and NS5A in facilitating HCV replication. This proposal may uncover novel therapeutic strategies to combat HCV.Read moreRead less
Fall Prevention And Physical Activity Promotion For Older Adults: Cluster Trial Of Effectiveness And Cost-effectiveness
Funder
National Health and Medical Research Council
Funding Amount
$1,291,950.00
Summary
This cluster randomised controlled trial will establish the impact on physical activity and falls of an intervention program that targets both physical activity and falls using assessment, advice and health coaching. The trial will involve 60 established groups of older people, recruited from local chapters of community organisations including Probus, the Older Women’s Network, registered clubs and church groups (estimated average group size of 10; total n = 600).
The Get Healthy Coaching Service To Reduce The Burden Of Low Back Pain: Effectiveness, Cost Effectiveness, And Scalability
Funder
National Health and Medical Research Council
Funding Amount
$1,108,389.00
Summary
Many improve after discharge from treatment for low back pain (LBP), however some experience worsening symptoms and seek costly additional health care. Get Healthy Service® is a free phone-based health coaching service that supports people to remain physically active, however there is no co-ordinated referral pathway to the service. We will test the effectiveness, cost-effectiveness and scalability of a discharge support system linking chronic LBP patients to the Get Healthy Service®.
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.
A Scalable Intervention For Increasing Vigorous Physical Activity Among Older Adolescents: The ‘ Burn To Learn ’ Cluster RCT
Funder
National Health and Medical Research Council
Funding Amount
$636,912.00
Summary
Physical inactivity has been described as a global pandemic and only 15% of Australian adolescents are sufficiently active. The pressure to perform in major school assessments drives many older adolescents to sacrifice physical activity to maximise academic performance. Our team has designed a time-efficient solution to increase physical activity in senior high school students using high intensity interval training which will be evaluated using a cluster randomised controlled trial.
Improving Weight Loss By Intermittent Use Of Very Low Energy Diet: The TANGO Diet Trial (Temporary Phases Of Accelerated Weight Loss For Noticeably Greater Outcomes)
Funder
National Health and Medical Research Council
Funding Amount
$660,736.00
Summary
Very low energy diet (VLED) is being increasingly used for the treatment of obesity, but the resultant weight loss is usually transient, partly because it induces powerful adaptive responses that inhibit weight loss and promote regain. We have shown that 'taking a break from dieting' for 2 weeks reduces these adaptive responses. In this project we will thus test whether weight loss outcomes with VLED can be improved via intermittent use, where periods on the VLED are alternated with 'breaks'.
Assembly And Transport Of Herpes Simplex Virus Within Neurones
Funder
National Health and Medical Research Council
Funding Amount
$475,500.00
Summary
Herpes simplex virus (HSV) enters the human body via the skin before entering the termini of nerve cell processes. It is transported along these processes to the body of the nerve cell. HSV lies dormant within these nerve cell bodies near the spinal cord in most people. Intermittently the virus reactivates and is transported back down the nerve cell processes to the skin where it causes blisters-ulcers or is shed without causing symptoms. The aim of this grant is to determine how HSV is transpor ....Herpes simplex virus (HSV) enters the human body via the skin before entering the termini of nerve cell processes. It is transported along these processes to the body of the nerve cell. HSV lies dormant within these nerve cell bodies near the spinal cord in most people. Intermittently the virus reactivates and is transported back down the nerve cell processes to the skin where it causes blisters-ulcers or is shed without causing symptoms. The aim of this grant is to determine how HSV is transported and assemblied within nerve cells at the molecular level. Recent discoveries have shown how virus transport in nerve cells is dependent on interactions between specific viral proteins and cellular motor proteins. Such information on viral transport and assembly mechanisms will allow development of inhibitors of these processes which may be candidates for use as antivirals for control of recurrent herpes simplex. In addition, this information will allow the virus to be exploited for use in gene therapy to introduce DNA into human nerve cells to correct genetic abnormalities.Read moreRead less