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
Functional Evaluation Of BRCA1 & BRCA2 Unclassified Sequence Variants And Identification Of Critical Pathogenic Domains.
Funder
National Health and Medical Research Council
Funding Amount
$331,312.00
Summary
The major genes that predispose to hereditary breast cancer are called BRCA1 and BRCA2. Most mutations in these genes cause the protein product to be truncated and inactive. However there are many families in which such truncating mutations are not found, but instead there are sequence changes that slightly alter the protein product. It is often difficult to predict whether these sequence variants are likely to cause hereditary breast cancer simply by looking at the position and nature of the se ....The major genes that predispose to hereditary breast cancer are called BRCA1 and BRCA2. Most mutations in these genes cause the protein product to be truncated and inactive. However there are many families in which such truncating mutations are not found, but instead there are sequence changes that slightly alter the protein product. It is often difficult to predict whether these sequence variants are likely to cause hereditary breast cancer simply by looking at the position and nature of the sequence change. Consequently, it is not possible to offer informative genetic counselling to these women or their at-risk family members. Assessment of the potential pathogenicity and functional significance of these unclassified sequence variants will be directly useful with regard to the clinical management of these women and their families, and will develop our current understanding of how different domains of these genes contribute to their role as cancer susceptibility genes.Read moreRead less
Evaluation Of Unclassified Variants Of BRCA1 And BRCA2 Using A Multifactorial Approach
Funder
National Health and Medical Research Council
Funding Amount
$456,495.00
Summary
The major genes that predispose to hereditary breast cancer are called BRCA1 and BRCA2. Most mutations in these genes cause the protein product to be truncated and inactive. However there are many families in which such truncating mutations are not found, but instead there are sequence changes that may slightly alter the protein product. It is often difficult to predict whether these sequence variants are likely to cause hereditary breast cancer simply by looking at the position and nature of th ....The major genes that predispose to hereditary breast cancer are called BRCA1 and BRCA2. Most mutations in these genes cause the protein product to be truncated and inactive. However there are many families in which such truncating mutations are not found, but instead there are sequence changes that may slightly alter the protein product. It is often difficult to predict whether these sequence variants are likely to cause hereditary breast cancer simply by looking at the position and nature of the sequence change. Consequently, it is not possible to offer informative genetic counselling to these women or their at-risk family members. Assessment of the potential pathogenicity and functional significance of these unclassified sequence variants will be directly useful with regard to the clinical management of these women and their families, and will develop our current understanding of how different domains of these genes contribute to their role as cancer susceptibility genes. In addition, some of our experiments to classify variants may be useful as a screening tool to identify carriers of mutations, and so prioritize them for mutation screening.Read moreRead less
Phylogeny As A Basis For Molecular Identification Of Pathogenic Fungi
Funder
National Health and Medical Research Council
Funding Amount
$440,750.00
Summary
Pathogenic fungi are becoming increasingly important in causing potentially life-threatening diseases in immunocompromised hosts (e.g. AIDS, transplant patients). Many of the emerging fungal pathogens are inherently resistent to triazole antifungal drugs and clinical responses to established drugs remain suboptimal, despite apparent sensitivity in the laboratory. Current techniques of fungal identification are insensitive, unspecific, slow, labour-intensive and require skilled personnel for the ....Pathogenic fungi are becoming increasingly important in causing potentially life-threatening diseases in immunocompromised hosts (e.g. AIDS, transplant patients). Many of the emerging fungal pathogens are inherently resistent to triazole antifungal drugs and clinical responses to established drugs remain suboptimal, despite apparent sensitivity in the laboratory. Current techniques of fungal identification are insensitive, unspecific, slow, labour-intensive and require skilled personnel for the ID of less common fungi. To improve clinical outcomes by prompt selection-initiation of the best antifungal regimes, and to truncate the interval from initiation of therapy to cure, early, accurate identification of the causative agent is crucial, making a fast identification to the species level after culture or direct from clinical specimens a necessity. A correct fungal identification can only be achieved if the phylogenetic relationships between the pathogenic organisms and their taxonomy is resolved. Gene detection is more reproducible than detection of morphological and biochemical differences. The proposal focuses on the establishment of an accurate phylogenetic system of pathogenic fungi, which will form the basis of a universally applicable molecular identification system and to develop a molecular reference database for human pathogenic fungi. This project will contribute sequence data of pathogenic fungi to the Tree of Life project. This project unites expertise in classical mycology, molecular biology, bioinformatics and infectious diseases, to develop an accurate phylogeny of medically important fungi, providing a unique opportunity to establish a quality controlled reference database accessible via the world-wide-web. This will provide a faster and more accurate ID of pathogenic fungi, which will lead to better clinical treatment.Read moreRead less