Macrophages are a key component of the immune system; thier functions include killing of pathogens as well as cancerous cells. Macrophage lineage cells are derived from stem cells within the bone marrow and thier differentiation, proliferation and survival is mediated by a particular growth factor termed colony stimulating factor-1 (CSF-1). The understanding of how macrophage lineage cells develop will help us to treat many diseases including certain cancers (such as leukemia), arthritis and inf ....Macrophages are a key component of the immune system; thier functions include killing of pathogens as well as cancerous cells. Macrophage lineage cells are derived from stem cells within the bone marrow and thier differentiation, proliferation and survival is mediated by a particular growth factor termed colony stimulating factor-1 (CSF-1). The understanding of how macrophage lineage cells develop will help us to treat many diseases including certain cancers (such as leukemia), arthritis and inflammation, and disorders of the immune system. The action of CSF-1 is mediated by the CSF-1 receptor (CSF-1R) which, when activated, controls gene regulation. In this proposal we will study CSF-1R activation and identify the genes regulated by CSF-1 with a view to characterize genes critical for macrophage development. These genes may provide potential targets for new pharmacological agents.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
Molecular Cloning And Expression Of Cytokine Genes Related To Induction Of Allograft Transplantation Tolerance In Rats
Funder
National Health and Medical Research Council
Funding Amount
$212,371.00
Summary
Cytokines are soluble proteins produced by leucocytes, and in many cases other cell types, which act as chemical communicators between cells, but not as effector molecules in their own right. Most of the cytokines are growth or differentiation factors and they generally act on cells within the haematopoietic system. In this grant application we will focus on the production of cytokines and antibodies to these cytokines, that are likely to be important in organ transplantation tolerance or organ ....Cytokines are soluble proteins produced by leucocytes, and in many cases other cell types, which act as chemical communicators between cells, but not as effector molecules in their own right. Most of the cytokines are growth or differentiation factors and they generally act on cells within the haematopoietic system. In this grant application we will focus on the production of cytokines and antibodies to these cytokines, that are likely to be important in organ transplantation tolerance or organ rejection. We would like to synthesize these cytokines using molecular biological techniques. These biological materials will be used to treat animals and study their biological effect on transplanted graft survival. If the cytokine treatment does prolong graft survival, what is the mechanisms involved in the immune responses will be further studied. Our aim is to develop strategies that couold be applied to help pateints with organ transplants and receive most specific therapies.Read moreRead less
A SYSTEMS BIOLOGY APPROACH TO SCREENING, DIAGNOSIS AND PROGNOSIS FOR LYSOSOMAL STORAGE DISORDERS
Funder
National Health and Medical Research Council
Funding Amount
$900,781.00
Summary
Lysosomal storage disorders (LSD) are inherited and, at present, can only be detected in children after symptoms are obvious. We are developing newborn screening for LSD to detect affected babies before the onset of irreversible symptoms. As most LSD babies appear normal at birth it is important to be able to predict disease severity or rate of disease progression; this will help doctors know when to give therapy, which therapy is best and provide families with appropriate genetic counseling.
Direct And Indirect Assessment Of 5 Ability Structures Underlying 7 Categories Of Childhood Psychopathology
Funder
National Health and Medical Research Council
Funding Amount
$263,311.00
Summary
This research has four main aims. First, we aim to obtain detailed knowledge of how normal children develop a range of different abilities, including motor coordination, language skills, the ability to understand other people, self-control, and general cognitive ability. Second, with this knowledge of normal development we will be able to identify cases in which normal development does not occur and to identify the exact ability area(s) in which development is abnormal. Patterns of abnormal deve ....This research has four main aims. First, we aim to obtain detailed knowledge of how normal children develop a range of different abilities, including motor coordination, language skills, the ability to understand other people, self-control, and general cognitive ability. Second, with this knowledge of normal development we will be able to identify cases in which normal development does not occur and to identify the exact ability area(s) in which development is abnormal. Patterns of abnormal development will be studied in children with one of seven disorders, including Autistic Disorder, Intellectual Disability, and Developmental Coordination Disorder. Third, we will assess whether deficits in some ability correspond to impairments in just one basic psychological structure (e.g., language deficits are related to impairment in the ability to recognise sounds) or whether they can be due to impairments in several structures (e.g., the ability to recognise faces or the ability to maintain attention). Finally, we will investigate whether and how impairments in one or more basic psychological structures can result in deficits in one or more of the ability areas that are the basis for the diagnosis of one or more developmental disorders. This research is expected to lead to an enhanced ability to assess the exact nature of any given developmental disorder which, in turn, should enhance clinical care of the child.Read moreRead less