Macrophages are important cells at the front-line of immunity where one of their main roles is to release anti-bacterial proteins. We will study the macrophage molecules, subcellular organelles and pathways that help to release these proteins to kill bacteria and fight infection. Our studies will identify new cellular targets for boosting immunity and treating inherited diseases with defective macrophage function.
Macrophages are white blood cells that provide front line defence against infection by initiating inflammatory responses by ingesting or phagocytosing microbes and by releasing soluble messengers (cytokines) to recruit other immune cells. These defensive functions require extensive trafficking of proteins within the macrophages. Protein trafficking is orchestrated in part by a family of membrane fusion proteins called SNAREs. By defining the relevant SNAREs, we have recently discovered a much ac ....Macrophages are white blood cells that provide front line defence against infection by initiating inflammatory responses by ingesting or phagocytosing microbes and by releasing soluble messengers (cytokines) to recruit other immune cells. These defensive functions require extensive trafficking of proteins within the macrophages. Protein trafficking is orchestrated in part by a family of membrane fusion proteins called SNAREs. By defining the relevant SNAREs, we have recently discovered a much acclaimed and novel pathway that allows efficient, combined cytokine secretion and phagocytosis in macrophages. Our studies proposed here will now expand on this discovery by comparing the phagocytic process, in terms of SNARE-mediated membrane and cytokine trafficking, for a wide range of microbes, highlighting differences that could provide new avenues for drug development. Moreover, since our strategy of using SNAREs to investigate and map trafficking pathways has proven so successful, we will now launch a major large-scale initiative to study ALL SNARE-mediated trafficking pathways in macrophages using a discovery pipeline of assays, including live cell imaging, we have developed. This will provide valuable information on many SNAREs including those associated with disease, and will elucidate trafficking pathways governing all macrophage actions in immunity, including cytokine secretion and antigen presentation. All of these pathways are highly relevant to current drug targets being used clinically or studied in inflammatory disease and for the development of vaccines.Read moreRead less
Role Of IGF Binding Protein-3 (IGFBP-3) And IGFBP-5 As Modulators Of Nuclear Hormone Signalling
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain ....The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain cells perform specialised functions. In test-tube experiments, IGFBP-3 and IGFBP-5 interact directly with the receptors that regulate the effects of these hormones. If the same thing happens inside the cell, IGFBP-3 and IGFBP-5 could change the way these receptors respond to signals from outside the cell. We will investigate what effect these IGFBPs have in living cells and in whole animals and how this may relate to human disease. If we are able to understand how IGFBP-3 and IGFBP-5 affect the way cells respond to vitamin A and D, then we may be able to develop new ways to treat certain human diseases.Read moreRead less
The role of the immune system in pain is emerging from recent discoveries, and may hold the key to novel pain treatments. Most people experience brief gut infections from food or contagion without long-term consequences. Many others suffer symptoms for years afterwards - probably the best example of immune-based pain. Our project investigates how immune cells communicate with sensory nerves, and how these communications change from both angles after gut infection or inflammation.
Transient Receptor Potential Channels (TRPs) As Transducers And Targets In Primary Visceral Afferents
Funder
National Health and Medical Research Council
Funding Amount
$669,130.00
Summary
Transient receptor potential, or TRP channels, are involved in generating many of the sensations we perceive, such as heat, cold, touch and pain. Some TRP channels are specialized to signal pain from visceral organs, which we must investigate if we are to find treatments for visceral pain, which are currently lacking.
Cognitive Impairments And Post Traumatic Stress Symptoms In Children With Traumatic Brain Injury: A Longitudinal Study
Funder
National Health and Medical Research Council
Funding Amount
$482,250.00
Summary
Traumatic brain injury in children is common with more than 2000 new cases a year in Queensland and Victoria alone. Many children who experience a brain injury go on to have long-term difficulties such as significant educational and social problems. Post-traumatic stress occurs in children following traumatic physical injury. However it is not clear to what extent this is so for children who have received a traumatic brain injury. Furthermore, when there is a traumatic brain injury and traumatic ....Traumatic brain injury in children is common with more than 2000 new cases a year in Queensland and Victoria alone. Many children who experience a brain injury go on to have long-term difficulties such as significant educational and social problems. Post-traumatic stress occurs in children following traumatic physical injury. However it is not clear to what extent this is so for children who have received a traumatic brain injury. Furthermore, when there is a traumatic brain injury and traumatic stress, it is not clear how these interact, how they influence long-term outcomes, and what factors such as pre-injury functioning and family support and distress mediate outcomes. These issues are very important since effective rehabilitation of children following traumatic brain injury is essential to maximise long-term functioning and minimise disability. To be effective, rehabilitation must be guided by the knowledge about key factors that determine the recovery process. This study aims to provide answers to these questions by following two cohorts of children (aged 6-14) over 18 months after receiving a traumatic brain injury. In total 240 children will be recruited from Brisbane and Melbourne hospitals. They will be assessed at three, six, twelve and eighteen months post-injury using measures of cognitive, psychological and social functioning. Information on parent distress and behaviours will also be obtained. The information obtained will provide the basis for the development of a specific rehabilitation strategy for children with traumatic brain injury, including information on strategies to help prevent any confounding impact of post-traumatic stress on recovery.Read moreRead less
20 Year Study Of Skin Cancer In A Queensland Community
Funder
National Health and Medical Research Council
Funding Amount
$396,415.00
Summary
Skin cancers are by far the commonest cancers diagnosed in Australia. Even though it is known that sun exposure in excess causes skin cancers there are complexities about the causes, especially of basal cell carcinoma (BCC) -the major type of skin cancer- that are still not understood. Relative intensity of sun exposure and perhaps its timing with respect to age in life may well be critical factors. We aim to study these causes in very great detail by collating information that has been gathered ....Skin cancers are by far the commonest cancers diagnosed in Australia. Even though it is known that sun exposure in excess causes skin cancers there are complexities about the causes, especially of basal cell carcinoma (BCC) -the major type of skin cancer- that are still not understood. Relative intensity of sun exposure and perhaps its timing with respect to age in life may well be critical factors. We aim to study these causes in very great detail by collating information that has been gathered over a 20 year period in a community-based skin cancer study in Nambour, Qld as well as performing some laboratory tests on skin cancer tissue collected from participants. This 3-year project will enable the full realisation of the potential of this esource-20 years in the making- with its wealth of information for answering questions about skin cancer decelopment and preventability. It should finally provide us with a clearer rationale for 'prevention of skin cancer' than is currently available. In addition we shall assess the costs of treatment of skin cancer in general and for the individual, and how much preventive practices for skin cancer might save the health budget, by using the releavnt data collected from this community sample.Read moreRead less
Mothers' History Of Mental Health Impairment And Its Impact During Mid-Life
Funder
National Health and Medical Research Council
Funding Amount
$421,580.00
Summary
There have been few specific studies of the health of women in mid-life. In mid-life, mental health impairment and health problems associated with biological and social transitions (e.g. menopause) are major concerns. National estimates indicate that between 15% and 20% of women in the mid-life age range have experienced a mental illness in the past year. The proportion of women experiencing a combination of emotional and physical symptoms, frequently associated with the menopause, is likely to ....There have been few specific studies of the health of women in mid-life. In mid-life, mental health impairment and health problems associated with biological and social transitions (e.g. menopause) are major concerns. National estimates indicate that between 15% and 20% of women in the mid-life age range have experienced a mental illness in the past year. The proportion of women experiencing a combination of emotional and physical symptoms, frequently associated with the menopause, is likely to be somewhat higher. This proposal involves merging information collected initially from 1981 onwards, with data on the mother's mental and physical health, to be collected in this follow-up. Women in this study (8556) were enrolled at their first obstetrical visit and they have been followed up shortly after the birth, when the child was 6 months, 5 years and 14 years. On each occasion extensive information has been obtained on the mother's mental and physical health, as well as on the child's health and development. This study will examine the chronicity of the mother's mental health symptoms over a 21-year period, and assess the association between her early mental health, the child's health and her current health status. This is the only large Australian cohort study to have followed a sample of women for 21 years. It will permit us to understand more of how women's health changes over time and the factors associated with these changes. It will provide the first large-scale study of factors influencing women's health transition through the menopause.Read moreRead less
Development Of Quality Indicators For The Frail Elderly In Acute Care
Funder
National Health and Medical Research Council
Funding Amount
$372,311.00
Summary
Frail older people are particularly vulnerable to a range of mishaps while in hospital. Good care can reduce the frequency and extent of these problems. Quality indicators (QIs) assist hospitals, and clinical service units within them, to appraise their performance, and to compare it to other hospitals. QIs for the measurement of outcomes for the frail aged in the acute care setting do not exist in Australia or overseas. We aim to develop these indicators during this study.