Structure-function Relationships Of Rye Grass Pollen Allergens And Preparation Of Hypoallergenic Mutants For Therapy
Funder
National Health and Medical Research Council
Funding Amount
$223,928.00
Summary
Grass pollen is an important cause of allergy (eg. hayfever, allergic asthma) world-wide affecting up to 30% of the population. In Australia, rye grass pollen is a clinically significant health problem costing $83-160 million per annum. At present, the main treatment of seasonal allergy is by pharmacotherapy with the use of crude extracts in specific immunotherapy which often causes large and annoying local skin reactions and may even cause anaphylaxis. Moreover, the use of crude extracts in dia ....Grass pollen is an important cause of allergy (eg. hayfever, allergic asthma) world-wide affecting up to 30% of the population. In Australia, rye grass pollen is a clinically significant health problem costing $83-160 million per annum. At present, the main treatment of seasonal allergy is by pharmacotherapy with the use of crude extracts in specific immunotherapy which often causes large and annoying local skin reactions and may even cause anaphylaxis. Moreover, the use of crude extracts in diagnosis of allergy among some atopic individuals may be inaccurate or ineffective. In the last eight years of my research, I have contributed significantly to the identification, characterisation and molecular cloning of grass pollen allergens. In this proposal, I aim to evaluate recombinant rye grass pollen allergens as standardised and more effective diagnostic reagents and, through the identification and better understanding of the allergenic segments of these proteins, to prepare recombinant mutants of the same proteins which are no londer allergenic. Avaliability of such non-allergenic protein reagents will provide safer immunotherapy in the future. Moreover, since the biolgical role, function and structure of such allergens in the grass pollen still remain largely unknown, I will aim to investigate this with the clinically significant allergens of rye grass pollen. Determination of biological function and structure of such allergens will allow their importance for the pollen-plant to be determined and, since function may be relevant to sensitisation of suceptible individuals to these allergens, these findings will stimulate the development of novel concepts in allergen prevention and therapy.Read moreRead less
Fine Mapping And Characterisation Of Polymorphic Immunoregulatory Genes In The Central MHC
Funder
National Health and Medical Research Council
Funding Amount
$529,656.00
Summary
The major histocompatibility complex (MHC) is a group of genes that is usually inherited as a block. The group includes the HLA genes which can serve as markers for neighbouring genes that are less well characterised. For example, some variant forms (polymorphisms) of the HLA genes mark differences in susceptibility to diabetes, lupus and IgA deficiency. We propose that this may be caused by variations in the neighbouring uncharacterised genes affecting control of persistent inflammation of vari ....The major histocompatibility complex (MHC) is a group of genes that is usually inherited as a block. The group includes the HLA genes which can serve as markers for neighbouring genes that are less well characterised. For example, some variant forms (polymorphisms) of the HLA genes mark differences in susceptibility to diabetes, lupus and IgA deficiency. We propose that this may be caused by variations in the neighbouring uncharacterised genes affecting control of persistent inflammation of various target organs. Evidence so far suggests a gene in the central MHC may be responsible. In this project we will study DNA from patients who have unusual combinations of HLA and other MHC genes, to further define which part of the MHC contains the critical immunoregulatory genes. Most genes in the MHC have now been identified by the Human Genome Project, so we will be able to select the most promising candidates in the region of interest. We will then use DNA of known HLA types to determine if the candidate genes vary between individuals. The function of interesting genes will then be investigated by creating cell lines carrying part of the gene in the reverse (anti-sense) orientation. This generates a reverse messenger (m) RNA which binds the normal mRNA and prevents synthesis of the protein. We will then examine which responses of the resultant cell lines are abnormal (eg: production of inflammatory mediators or cytokines). Having elucidated the functions our genes, we will overexpress each version that occurs in patients in cultured cells and look for differences in function. In parallel with this work, we will use laboratory mice with known combinations of MHC genes to establish the effects of particular genes in a live animal.Read moreRead less