Analysis Of Viral And Cellular Gene Expression During Human Cytomegalovirus Latent Infection Of Hematopoietic Cells
Funder
National Health and Medical Research Council
Funding Amount
$407,545.00
Summary
Human cytomegalovirus (HCMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing HCMV disease. Like other herpesviruses, after initial infection HCMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body a ....Human cytomegalovirus (HCMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing HCMV disease. Like other herpesviruses, after initial infection HCMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body and no infectious virus is made. However, when conditions are right the virus can awaken (ie reactivate) from its latent state, producing new infectious virus and disease. It is in immunosuppressed individuals such as transplant patients that viral latency and reactivation are of most medical concern, yet viral latency remains very poorly understood. This project has three major components. Firstly, we aim to continue studies which are defining what viral genes are active (ie expressed) during latent infection. Identification of these genes and determination of how they function may have profound implications to our understanding of latency. Secondly, we will examine how human cells are affected when they become latently infected. A new and exciting technology called DNA microarray now makes it possible to examine the expression of many thousands of genes in a single experiment. For the first time, we will be able to determine how the cell changes during latency and reactivation. The study of viral and cellular gene expression during latency may contribute to the development of drugs which interfere with the viruses ability to become latent or reactivate. Thirdly, we have preliminary results which suggest that latent HCMV may actively avoid detection by the immune system. In this project we also aim to determine the mechanism by which the virus interferes with the expression of molecules which are an essential component of our immune system.Read moreRead less
Viral And Host Cell Gene Expression During The Establishment And Maintenance Phases Of Human Cytomegalovirus Latency
Funder
National Health and Medical Research Council
Funding Amount
$149,250.00
Summary
Human cytomegalovirus (CMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing CMV disease. Like other herpesviruses, after initial infection CMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body and ....Human cytomegalovirus (CMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing CMV disease. Like other herpesviruses, after initial infection CMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body and no infectious virus is made. However, when conditions are right the virus can awaken (ie reactivate) from its latent state, producing new infectious virus and disease. It is in immunosuppressed individuals such as transplant patients that viral latency and reactivation are of most medical concern, yet viral latency remains very poorly understood. The overall aim of these studies is to provide a much better understanding of how CMV latency is established and maintained, with the ultimate goal of making advances for the design of anti-viral therapies to disrupt these processes. This project has three major components: Firstly, we aim to identify and characterise viral gene expression during the establishment of latency and these findings will have profound implications to our understanding of latency. Secondly, we will examine how human cells are affected when they become latently infected. A new and exciting technology called DNA microarray now makes it possible to examine the expression of many thousands of genes in a single experiment. For the first time, we will be able to determine how the cell changes during the establishment and maintenance phases of latency. Thirdly, we will apply microarray technologies to determine how human cell genes are altered in response to the expression of individual viral genes that are active during the latent phase of infection.Read moreRead less
New Drugs To Counteract The Side Effects And Premature Ageing Caused By Chemotherapy
Funder
National Health and Medical Research Council
Funding Amount
$577,658.00
Summary
During cancer treatment, commonly used chemotherapy drugs cause profound side effects that include pain, nausea, heart problems, hair loss and can affect almost every system in the body. Even after chemotherapy treatment has stopped, cancer survivors face an increased risk of diseases which resemble the effects of old age. We are testing newly discovered anti-ageing molecules for their ability to reduce these side effects, and drastically improve the quality of life for cancer patients.
Deciphering Mechanisms Of Liver Allograft Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$520,964.00
Summary
The liver has paradoxical properties: it is the site of effective immune responses to pathogens, but under some circumstances, it is known to induce harmless immune responses. Liver transplants are more readily accepted than other organ grafts in the absence of immunosuppressive drugs but little is known about the mechanisms that prevent an effective response. This proposal aims to unravel these mechanisms. This project will have important implications for transplantation studies.
Understanding The Mechanisms For Ameliorating/preventing Antipsychotic-induced Obesity In Early Life
Funder
National Health and Medical Research Council
Funding Amount
$576,496.00
Summary
There has been a sharp worldwide increase during the last decade in antipsychotic prescriptions (mostly “off-label”) to paediatric patients. One important issue is that antipsychotic drugs were developed for adult patients and normally have serious side-effects. This project will not only reveal the mechanisms of antipsychotic-induced obesity side-effects in youth, but will also explore intervention strategies for preventing antipsychotic-induced weight gain/obesity in paediatric patients.
Long-term Nerve Damage In Cancer Survivors: Identification Of Risk Factors And Optimal Assessment Strategies
Funder
National Health and Medical Research Council
Funding Amount
$850,172.00
Summary
Nerve damage following chemotherapy treatment leads to early treatment cessation and long-lasting disability, developing with commonly used chemotherapies. There is a critical need to understand the mechanisms, optimize clinical assessment and develop interventions to prevent nerve damage. This project is designed to detect the impact of long-term nerve damage in cancer survivors and develop a risk profile based on clinical, neurophysiological and genetic factors.
Benefit Of 2D-strain Surveillance In Improving Cardiovascular Outcomes In Cancer Patients Undergoing Cardiotoxic Chemotherapy
Funder
National Health and Medical Research Council
Funding Amount
$2,391,979.00
Summary
Cancer survivors are susceptible to heart failure (HF) caused by heart muscle damage from chemotherapy. The current testing for this problem is based on a measure that cannot identify minor changes of cardiac function. Cardiac strain is a sensitive new marker of cardiac function which is predictive of overt dysfunction & HF. This study seeks to identify whether strain can be used to assign treatments that lead to improved cardiac function and are eventually associated with a reduction in HF.
Preserving Ovarian Function During Chemotherapy And Old Age
Funder
National Health and Medical Research Council
Funding Amount
$425,048.00
Summary
Chemotherapy treatment and the natural ageing process leads to ovarian failure and infertility. For young cancer survivors, chemotherapy induced infertility is devastating, and like aged women, leads to hormonal changes that lead to osteoporosis, diabetes, obesity, and neurodegeneration. Here, a new class of molecules will be tested for their ability to prevent and reverse infertility folllowing chemotherapy treatment, and in old age. These findings will improve the healthy lifespan of women.
Managing an ageing population for income adequacy and fiscal sustainability. This project aims to improve understanding of the impacts of existing key reforms intended to ease fiscal pressures associated with population ageing. The right mix of retirement income policies is vital to Australia's fiscal sustainability, however the effectiveness of existing policies is unknown. The project expects to identify impacts of key reforms on employment, re-training, income, savings and future retirement i ....Managing an ageing population for income adequacy and fiscal sustainability. This project aims to improve understanding of the impacts of existing key reforms intended to ease fiscal pressures associated with population ageing. The right mix of retirement income policies is vital to Australia's fiscal sustainability, however the effectiveness of existing policies is unknown. The project expects to identify impacts of key reforms on employment, re-training, income, savings and future retirement income and public pension receipt. The project will develop a new tax records-based dataset to facilitate future research on tax and welfare systems.Read moreRead less