Use Of Expression Profiling To Identify Genes Influencing Cardiovascular Risk In The Norfolk Island Population Isolate
Funder
National Health and Medical Research Council
Funding Amount
$697,409.00
Summary
This study will use a unique population isolate from Norfolk Island. We aim to identify genes that play a role in cardiovascular disease risk. Norfolk has a population of ~1200 permanent residents, most of whom are direct descendents of 18th century English Bounty mutineers and Polynesian women. We will undertake gene expression mapping to identify genomic loci that influence cardiovascular disease using samples from this population isolate.
From Linkage To Genes Conferring Susceptibility To Schizophrenia: Investigation Of Candidate Genes On Chromosome 6p
Funder
National Health and Medical Research Council
Funding Amount
$462,250.00
Summary
Schizophrenia is a potentially disabling disorder with severe impact on the individual, the family and the community. The risk that a child born today will develop schizophrenia is about 1%. Genetic factors play a major predisposing role in schizophrenia, but environmental factors contribute as well. The molecular causes of schizophrenia are yet to be discovered, as knowledge about complex brain functions and their disorders is rapidly increasing. The identification and characterisation of genet ....Schizophrenia is a potentially disabling disorder with severe impact on the individual, the family and the community. The risk that a child born today will develop schizophrenia is about 1%. Genetic factors play a major predisposing role in schizophrenia, but environmental factors contribute as well. The molecular causes of schizophrenia are yet to be discovered, as knowledge about complex brain functions and their disorders is rapidly increasing. The identification and characterisation of genetic factors involved in brain function and dysfunction is likely to bring about novel insights into the neural and molecular mechanisms underlying schizophrenia. There is evidence, reported by several groups including our own, that genes, co-segregating with schizophrenia in families are located in a region on chromosome 6p. By fine-grain genetic dissection of this region, we and others have found that the gene coding for the protein dysbindin is associated with schizophrenia. Our aim is to identify the DNA variant(s) in the dysbindin gene, as well as variants in other candidate genes that may be located in chromosome 6p. We will use state-of-the art methods and information on genes and DNA variants, made available through the Human Genome Project. Once genetic variants are identified, we will analyse gene expression in post mortem brain tissue of persons with schizophrenia and study the distribution and function of the proteins coded by the identified genes. Our ultimate goal is to identify specific genetic factors involved in the brain dysfunction characterising schizophrenia. If successful, this should lead to clues about the causes of the disorder. In addition, the study will contribute to the development of methods for early diagnosis and prevention. Possibly, the most important outcome will be the identification of molecular targets for novel and more specific pharmacological treatments that may eventually replace current symptom-oriented antipsychotic medications.Read moreRead less
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
Primary central nervous system (CNS) tumours, arising in the brain and spinal cord, are the leading cause of cancer-related deaths in children less than 15 years of age. Medulloblastomas and other primitive neuroectodermal tumours (PNETs) are the most common form of primary childhood brain tumours, accounting for 25-30% of cases. Despite notable recent advances in our understanding of the molecular genetic basis of malignancies, the pathogenesis of CNS PNETs remains obscure. To address this prob ....Primary central nervous system (CNS) tumours, arising in the brain and spinal cord, are the leading cause of cancer-related deaths in children less than 15 years of age. Medulloblastomas and other primitive neuroectodermal tumours (PNETs) are the most common form of primary childhood brain tumours, accounting for 25-30% of cases. Despite notable recent advances in our understanding of the molecular genetic basis of malignancies, the pathogenesis of CNS PNETs remains obscure. To address this problem, we propose to apply a novel combinatorial approach for the identification of PNET tumour suppressor genes utilising both representational difference analysis (RDA) and microarray expression profiling. Data from this study will help to elucidate the molecular pathways that are compromised in the initiation and growth of PNETs. This information will have direct implications for the development of improved diagnostic and prognostic indicators necessary for the design of more effective therapeutic strategies for the treatment of PNET patients.Read moreRead less
Structural Basis For Inhibition Of Malaria Invasion By Targeting The Apical Membrane Antigen Of Plasmodium Falciparum.
Funder
National Health and Medical Research Council
Funding Amount
$434,134.00
Summary
3 million children die every year from malaria infections. A leading vaccine candidate is a protein from the malaria parasite called AMA1. Humans that have been infected with malaria make antibodies to this protein which can kill parasites, however little is known about how this occurs. We aim to identify regions of the protein that generate antibodies that prevent malaria parasites from invading human cells and help in the search for a vaccine against malaria.