Stress-induced Genomic Instability As A Driver Of Adaptive Responses In Human Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$690,426.00
Summary
Growing experimental evidence suggests human cancer cells use evolutionary conserved programs to regulate their mutation rates in response to pharmacological agents, accelerating adaptation and the emergence of resistance. The purpose of our study is to identify the common molecular pathways and genetic mechanisms driving the regulation of mutation rates. Targeting of these pathways using a new generation of “anti-evolution” drugs is an attractive possibility for novel therapeutic approaches.
Optimising disease surveillance to support decision-making. COVID-19 has demonstrated the critical role of epidemic data and analytics in guiding government response to pandemic threats, reducing disease and saving lives. The demand for epidemic analytics for response to threats of national significance will only grow. The goals of this project are to 1) determine the combination(s) of surveillance methods that provide the most useful data for epidemic analysis and 2) translate these findings in ....Optimising disease surveillance to support decision-making. COVID-19 has demonstrated the critical role of epidemic data and analytics in guiding government response to pandemic threats, reducing disease and saving lives. The demand for epidemic analytics for response to threats of national significance will only grow. The goals of this project are to 1) determine the combination(s) of surveillance methods that provide the most useful data for epidemic analysis and 2) translate these findings into the blueprint for a next-generation infectious disease surveillance system for Australia. We will use a simulation-evaluation approach, coupling methods from infectious disease modelling with those from information theory optimal design. Outcomes will enable more tailored and effective pandemic response.Read moreRead less
Norovirus Infection At The Stress Granule-PKR-p-elF2α Axis
Funder
National Health and Medical Research Council
Funding Amount
$505,967.00
Summary
This project application will aim to investigate and understand how viruses that cause vomiting and diarrhoea are able to infect, proliferate and spread within the human body. It aims to address how viruses are able to avoid and replicate in the presence of an effective immune response. We have evidence showing that Noroviruses are able to exploit certain antiviral proteins to paradoxically aid in virus replication and survival.
THE EFFECT OF STRESS AND ENVIRONMENTAL ENRICHMENT ON DISEASE PROGRESSION IN MESIAL TEMPORAL LOBE EPILEPSY
Funder
National Health and Medical Research Council
Funding Amount
$578,201.00
Summary
Mesial temporal lobe epilepsy, the most common form of drug-resistant epilepsy in adults, is a progressive neurodegenerative condition for which there is currently no effective disease modifying treatment. This proposal will explore whether co-morbid stress accelerates disease progression in MTLE, and whether targeting stress pathways by medical and environmental manipulations can mitigate against this.
Testing A Tailored, Evidence-based Education Intervention To Enhance Outcomes For Patients Commencing Chemotherapy
Funder
National Health and Medical Research Council
Funding Amount
$311,250.00
Summary
This project tests an innovative education program aimed at reducing the physical and psychosocial burden experienced during a course of cancer chemotherapy. The aim of the study is to reduce the burden and distress associated with cancer chemotherapy. Cancer chemotherapy is associated with physical (nausea, fatigue, hair loss, infection) and psychosocial (fear, anxiety, worry about family) effects that cause significant distress. Patients experience a highly level of pre-treatment anxiety and f ....This project tests an innovative education program aimed at reducing the physical and psychosocial burden experienced during a course of cancer chemotherapy. The aim of the study is to reduce the burden and distress associated with cancer chemotherapy. Cancer chemotherapy is associated with physical (nausea, fatigue, hair loss, infection) and psychosocial (fear, anxiety, worry about family) effects that cause significant distress. Patients experience a highly level of pre-treatment anxiety and for many this distress lasts across the course of treatment. Over the past decade there has been a dramatic shift in chemotherapy delivery to the outpatient setting. This means that patients are now responsibile for monitoring their own health at home and may need to use self-care strategies to deal with the many adverse effects of treatment. Pre-treatment education has usually focused on providing information about the facts of treatment, i.e. likelihood of nausea, rather than preparing the patient for the experience of treatment or helping them to manage the self-care demands associated with receiving treatment in the outpatient setting. The innovative education program tested here is the first of its type to draw on high level research evidence about preparing patients for potentially threatening medical procedures, tailoring this education to the individual situation of the patient and coaching the patient to implement evidence-based self-care behaviours and to use stress reduction techniques across the course of treatment.Read moreRead less
Modulating Immune Responses By Targeting Dendritic Cells Using Dendritic Cell Specific Markers.
Funder
National Health and Medical Research Council
Funding Amount
$197,750.00
Summary
The ability to modulate immune responses would have major health benefits. Dendritic cells (DC) are key regulators of the immune system. Different types of DC possess different cell surface molecules and have differing regulatory functions. We have identified four novel DC surface molecules that can be used to target different types of DC. We aim to use antibodies against these molecules to either enhance the effectiveness of vaccines or to suppress autoimmune diseases.
Unravelling The Mechanism Of MHC Class-I Associated Drug Hypersensitivities
Funder
National Health and Medical Research Council
Funding Amount
$566,308.00
Summary
Some drugs cause adverse reactions that are life threatening. We think these reactions are mediated by killer T cells as they are genetically controlled by immune response genes that normally guide immunity to microbes. We will study immune reactions to the drug abacavir, used to treat HIV (AIDS); allopurinol used to prevent gout and carbamazepine, used to treat epilepsy. The study may also help devise better treatments for patients who experience severe forms of these reactions.
The Mezzanine T Cell Response: Intervening At The Coal Face
Funder
National Health and Medical Research Council
Funding Amount
$765,585.00
Summary
In an initial immune response, specialised cells in lymph nodes tell T cells to multiply; the stimulated T cells depart and enter target tissue (e.g. lung in the case of flu). We describe a new response whereby the target tissue itself can tell T cells to multiply further. This response in target tissues reveals a new way of altering immune responses. This is especially important as in many diseases, the primary lymph node response has already occurred, so cannot be therapeutically intervened.
C-Jun N-terminal Kinase Actions In The Response To Stress
Funder
National Health and Medical Research Council
Funding Amount
$480,127.00
Summary
All cells in our body sense and respond to stressful changes in our environment. We are focused on enzymes called JNKs that relay this information, and so form part of the key response pathways. JNKs are now being evaluated as new drug targets for the treatment of diseases including diabetes and stroke, but we know very little about how JNKs work in stressed cells. We will define new partners for the JNKs and in so doing reveal new information on the stress-activated events they regulate.
A Cluster RCT Of A Novel Psychological Intervention To Reduce Depression Among At-risk Older Adults Transitioning To Residential Aged Care
Funder
National Health and Medical Research Council
Funding Amount
$893,152.00
Summary
Depression is common in aged care facilities, with many older adults finding the transition extremely difficult. We have developed a simple intervention to help new residents, including those with dementia, to adjust to life in aged care. This program focuses on key aspects of psychological wellbeing, and is designed for widespread use in aged care. We will evaluate the intervention to determine if it is superior to current care approaches in reducing depression and improving quality of life.