Mimetics Of Natural Triggers Of Innate Immunity As Vaccines
Funder
National Health and Medical Research Council
Funding Amount
$241,650.00
Summary
Knowledge of what properties of an antigen allow it to induce an immune response is central to our understanding of how we fight disease and how we can vaccinate effectively against disease. The fact that an antigen is foreign to the host is not in itself sufficient for it to initiate the series of events that must take place in order to activate B and T lymphocytes, the cells involved in immunity. For vaccine purposes, antigens must be delivered with substances called adjuvants to be effective. ....Knowledge of what properties of an antigen allow it to induce an immune response is central to our understanding of how we fight disease and how we can vaccinate effectively against disease. The fact that an antigen is foreign to the host is not in itself sufficient for it to initiate the series of events that must take place in order to activate B and T lymphocytes, the cells involved in immunity. For vaccine purposes, antigens must be delivered with substances called adjuvants to be effective. There is very little known about how adjuvants actually work but many of the highly effective experimental adjuvants contain an immunostimulant which is usually either whole dead bacteria or components of the cell walls of bacteria or other organisms. From evidence emerging in the literature and our own experimental observations, we have begun to understand the requirements for and the chain of events leading to immune response induction. The interaction of certain lipid-containing groups, present on antigens from pathogenic organisms, with a specialised type of cell, the dendritic cell, is a key event in this process. We have designed synthetic mimics of lipid-containing moieties from bacteria and coupled them to unrelated parts of viral proteins. We showed that these lipopeptides can elicit potent anti-viral immune responses and long lived memory responses. The experiments outlined in this proposal will examine the interaction of these and other second generation lipopeptides with dendritic cells. We will determine whether these can bind to particular molecules on the dendritic cell surface to initiate a specific series of signals leading to immune induction and if so we will seek to use different lipid groups to trigger the immune response in different and predictable ways. The outcomes of this work may have a major impact on the design of new vaccines as well as increase our understanding of how the immune system is triggered to respond to invading organisms.Read moreRead less
Randomised Controlled Trial Of Therapeutic Pulmonary Lavage In Meconium Aspiration Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$182,550.00
Summary
Meconium aspiration syndrome (MAS) is a serious respiratory disease of full term infants, which can lead to very severe respiratory failure. It is caused by the inhalation of meconium, the secretion of the fetal intestine, into the lung at or prior to delivery. As a result, the airways and air sacs within the lung are damaged, leading to difficulty with breathing and poor oxygen levels. About one-third of all infants with MAS require mechanical ventilation in the first days of life, and are ofte ....Meconium aspiration syndrome (MAS) is a serious respiratory disease of full term infants, which can lead to very severe respiratory failure. It is caused by the inhalation of meconium, the secretion of the fetal intestine, into the lung at or prior to delivery. As a result, the airways and air sacs within the lung are damaged, leading to difficulty with breathing and poor oxygen levels. About one-third of all infants with MAS require mechanical ventilation in the first days of life, and are often extremely difficult to manage. At present, the main treatments given to a ventilated infant with severe MAS are supportive, rather than curative. Lung cleansing procedures are not part of routine care in this condition, even though removal of meconium from the lung may reduce the amount of damage that occurs. This project is a randomised controlled trial of a lung cleansing procedure called lung lavage in ventilated infants with severe MAS. During the lung lavage, a quantity of cleansing fluid containing a natural substance called surfactant is introduced into the lung, and then removed by suctioning. This procedure cleanses the lung of some of the meconium, and in preliminary testing, appears to be safe and well-tolerated even in the sickest infants. In the proposed trial, we will randomly allocate ventilated infants with severe MAS to receive either a lung lavage procedure, or routine care. This will take place within 24 hours of birth. We are looking to see whether the lavage procedure shortens the duration of ventilation, oxygen therapy or hospitalisation. Because there are only a small number of ventilated infants with MAS at any one centre per year, we will involve as many Australian neonatal intensive care units as we can in the study. We aim to enrol 66 infants in the trial, of whom half will receive lavage therapy.Read moreRead less
Impact Of The Refugee Application Process On The Psychiatric Status Of Traumatized Asylum Seekers: A Prospective Study
Funder
National Health and Medical Research Council
Funding Amount
$147,859.00
Summary
Although the numbers of persons who identify themselves as fleeing from persecution (asylum seekers) residing in Western countries has increased substantially in the last decade, very little research has been undertaken on the psychiatric and physical health of this group. The only studies published in professional journals have been produced by members of the applicant team. The results indicate that approximately 50% have suffered gross human rights violations including torture, detention in c ....Although the numbers of persons who identify themselves as fleeing from persecution (asylum seekers) residing in Western countries has increased substantially in the last decade, very little research has been undertaken on the psychiatric and physical health of this group. The only studies published in professional journals have been produced by members of the applicant team. The results indicate that approximately 50% have suffered gross human rights violations including torture, detention in concentration camps and brainwashing, and 37% are affected by ongoing posttraumatic stress disorder (PTSD) - terrifying memories of past abuses, avoidance of experiences that trigger such memories, social withdrawal, and constant anxiety. The research has also shown that psychiatric symptoms may be worsened by the fears and insecurities associated with the asylum seeking process, but the exact impact of stresses such as rejection of their primary application at 2-3 months, could not be determined. We therefore aim to conduct the first study of its kind that traces the impact of such stresses on the mental health of asylum seekers. In addition, we will track asylum seekers' general health problems and the difficulties they may experience in accessing basic medical health services. This evidence will provide scientific confirmation of how stress can worsen PTSD; indicate that some asylum seekers may be in special need of support throughout the asylum assessment process; assist policy makers to re-assess the methods and processs of assessing asylum claims; and provide impetus to establishing better services for the medical and psychiatric problems faced by asylum seekers.Read moreRead less
MICROFABRICATED DEVICES: A SIGNIFICANT ADVANCE FOR THE DETECTION AND MOLECULAR ANALYSES OF CIRCULATING CANCER CELLS?
Funder
National Health and Medical Research Council
Funding Amount
$422,107.00
Summary
Using advanced microfabrication concepts, this project aims to develop a platform technology able to capture tumour cells circulating in the blood of cancer patients. Although present only in extremely small numbers, these cells provide invaluable insights into the pathophysiology of the disease and consequently provide vital diagnostic and prognostic information. Molecular analyses of these cancer cells could ultimately enable the design of improved and personalized cancer treatment.