I am a research scientist measuring inhaled and exhaled bioaerosols, such as viruses and allergens, to determine their clinical role in human respiratory diseases, particularly asthma.
Mechanisms And Treatment Of Early Life Chlamydial Infection And Associated Asthma
Funder
National Health and Medical Research Council
Funding Amount
$616,195.00
Summary
Asthma is a serious respiratory disease that results from certain immune responses to allergens and there are no cures. Immune responses and lung structure may be permanently altered by respiratory chlamydial infection early in life that leads to reduced lung function and asthma but how this occurs is unknown. In this project we will determine how early life infections affect immune responses, lung function and asthma and test novel treatments and preventions for infection-associated asthma.
Fine Mapping Of Genes Underlying Asthma And Eosinophilia
Funder
National Health and Medical Research Council
Funding Amount
$278,000.00
Summary
Asthma is the fourth most common chronic disease in Australia, and is increasing in incidence. Genetic factors are known to be important modifiers of disease risk, and several genes have been reported in the literature as being involved in either causing asthma or altering response to therapy. Immunoglobulin E (IgE) level and eosinophil count are two factors known to be increased in the blood of asthmatics. In two studies by our group, one of asthma in families, the other of healthy adolescent t ....Asthma is the fourth most common chronic disease in Australia, and is increasing in incidence. Genetic factors are known to be important modifiers of disease risk, and several genes have been reported in the literature as being involved in either causing asthma or altering response to therapy. Immunoglobulin E (IgE) level and eosinophil count are two factors known to be increased in the blood of asthmatics. In two studies by our group, one of asthma in families, the other of healthy adolescent twins, we showed these measures to be genetically linked to two different regions in the genome. Closer examination of these regions found several genes that might be responsible for the linkage. In the present study, we plan to test which of these candidate genes actually causes elevated IgE level or eosinophil count. The approach is to compare the frequency of a putative gene in a child expressing that phenotype to that in their parents. Each child receives one copy of a gene from the father, and one from the mother, making up a complete genotype (two possibly different versions or alleles of the gene). Since each parent transmitted only one allele to the child, the remaining allele from each parent can be used to create a normal control genotype, that is guaranteed to come from the same ethnic background as the asthmatic child. Therefore, we will collect replacement blood samples in those familes where all the previously DNA has been used up in our earlier study. We will extract DNA, and measure the genotypes of parents and children at the 6 genes in our two regions that we think most likely to be involved in eosinophil count or IgE level. This family based test will allow us to decide which genes are genuinely associated with asthma in our population. We will also test if these genes interact with other genes thought to be asthma risk factors. Identification of novel genes involved in asthma will help understand and ultimately treat this condition.Read moreRead less
Role Of Zinc In The Respiratory Epithelium And Asthma
Funder
National Health and Medical Research Council
Funding Amount
$224,250.00
Summary
This project will use a panel of Zinquin-derived Zn fluorophores developed in our laboratory, as well as probes for the mammalian family of vesicular ZnT transporters, to carry out a study of the normal physiology of Zn in the respiratory system and potential abnormalities of this in patients with chronic inflammatory respiratory disease (asthma, COPD, chronic smoking). Chronic inflammatory diseases of the respiratory tract affect a significant proportion of the Australian community. For example ....This project will use a panel of Zinquin-derived Zn fluorophores developed in our laboratory, as well as probes for the mammalian family of vesicular ZnT transporters, to carry out a study of the normal physiology of Zn in the respiratory system and potential abnormalities of this in patients with chronic inflammatory respiratory disease (asthma, COPD, chronic smoking). Chronic inflammatory diseases of the respiratory tract affect a significant proportion of the Australian community. For example, asthma affects 12% of adults and amongst these, 15% waken weekly or more often with their asthma while 6% are hospitalized annually. There is a need to understand the basic mechanisms underlying these diseases so that new strategies can be developed to modify bronchocondtriction and inflammation. The project will provide new knowledge concerning the physiology of Zn in the respiratory epithelium and interactions between Zn deficiency and oxidants on injury in the respiratory tract. The usefulness of easily accessible nasal epithelial cells as a measure of Zn and Zn transporter levels deeper in the respiratory tract will be assessed. The project encompasses a number of fields and utilizes in vitro cellular and animal models, as well as tissues from human subjects.Read moreRead less
Many approaches to the prevention and treatment of allergy and associated asthma are dependent on the identification of the allergens producing the inflammation. This applies to new methods of determining the exposure to allergens and measuring the effectiveness of procedures which minimise allergen exposure. Diagnostic and immunotherapeutic measures require reliable preparations of allergens. The presence of important allergens in extracts however can be variable and often low so it important t ....Many approaches to the prevention and treatment of allergy and associated asthma are dependent on the identification of the allergens producing the inflammation. This applies to new methods of determining the exposure to allergens and measuring the effectiveness of procedures which minimise allergen exposure. Diagnostic and immunotherapeutic measures require reliable preparations of allergens. The presence of important allergens in extracts however can be variable and often low so it important that the allergens be identified and monitored. It is also important that new forms of immunotherapy being developed consider the responses to all allergens. Allergy to the cat is, behind house dust mite, the second most frequent allergy associated with asthma in most developed countries and brief exposure to a cat frequently induces life-threatening attacks. Almost all of the study of cat allergens have concentrated on a single allergen called Fel d 1. Although it importance is undisputed critical reading of the literature show it is only responsible for 50% of the IgE binding in cat extracts and recent work on cross allergy to cat and dogs and experimental therapy based on Fel d 1 point to the importance of other allergens. Experience with other source of allergens has shown that at least several allergens are usually important. It is also apparent from other studies that some allergens which are difficult to detect in extracts, and cannot be readily studied by immunochemistry are important. This project will use both cDNA cloning and immunochemistry to identify and characterize the other cat allergens and determine there relative importance. In particular it intended that they can be used, along with Fel d 1, to develop new types of immunotherapy.Read moreRead less
Inhibition Of Allergic Airway Inflammation By Nanoparticles
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
Inhaled air pollution particulate matter causes asthma exacerbations, with 'ultrafine' nanoparticles thought to play a major role. Unexpectedly, we recently found that, by contrast, administration of inert ultrafine nanoparticles prevents allergic airway inflammation. We will identify the key particle physical and chemical properties associated with this novel type of disease inhibition, study particle effects in clinically-relevant disease models and identify mechanisms of action.
Mimotopes For The Investigation And Therapy Of Allergic Disease
Funder
National Health and Medical Research Council
Funding Amount
$203,296.00
Summary
10% of children now use regular asthma medication. The current treatments dampen allergic inflammation but 25% of asthmatic children, all under high medication, need multiple visits to the doctor, emergency treatment or hospitalisation,. Immunotherapy has, since 1911, used repeated injections of allergens. The end result has often been successful and lasting but the response has been unpredictable and requires years of multi-injection treatment. The challenge is to develop effective, applicable ....10% of children now use regular asthma medication. The current treatments dampen allergic inflammation but 25% of asthmatic children, all under high medication, need multiple visits to the doctor, emergency treatment or hospitalisation,. Immunotherapy has, since 1911, used repeated injections of allergens. The end result has often been successful and lasting but the response has been unpredictable and requires years of multi-injection treatment. The challenge is to develop effective, applicable immunotherapy which, like vaccines use few injections. Mimotopes provide a new opportunity. Studying the parts of the allergens recognized by the immune system (epitopes) can reveal important phenomena undetectable with whole allergens; and single epitopes may be a powerful avenue to effective immunotherapy. The therapy can be targeted to a selected arm of the immune system for maximal effect and the immediate side effects induced by cross linking antibodies with two epitopes can be avoided. Allergens interact with two types of lymphocyte, the T and B cells. T-cell epitopes can be easily studied because they comprise short regions of proteins which can be synthesized. B-cell (and antibody) epitopes are shapes formed by the interaction of several parts of a protein which cannot be represented by a simple sequence. The mimotope technology uses random peptides to obtain a shape which mimics the B-cell epitope. Here mimotopes will be produced and used to study the common specificities recognized in allergic responses to house dust mite allergens to develop new types of therapy. Importantly recent information shows that B-cell epitopes can be used to modify both T and B-cell function.Read moreRead less