Post-GWAS Functional Characterisation Of Breast Cancer Susceptibility Loci
Funder
National Health and Medical Research Council
Funding Amount
$764,632.00
Summary
Recent studies have identified regions within the human genome in which DNA sequence variations are associated with an increased risk of breast cancer. Several of these regions do not contain any known genes, suggesting that regulatory DNA sequences are responsible for the associated risk. The aim of this proposal is to identify and characterise these DNA sequences. Understanding how sequences variations in these regions contribute to breast cancer will provide novel avenues for therapy.
Estrogen signalling in gonadotropes. Estrogen action is a normal prerequisite for cyclic function of reproduction in the female, but little is known about how this important hormone acts in the relevant cells of the pituitary gland (gonadotropes). In order to gain information on normal function, we will conduct studies on gonadotropes treated with estrogen in a range of paradigms. The information will be valuable in understanding normal reproduction, but will also form the basis of further studi ....Estrogen signalling in gonadotropes. Estrogen action is a normal prerequisite for cyclic function of reproduction in the female, but little is known about how this important hormone acts in the relevant cells of the pituitary gland (gonadotropes). In order to gain information on normal function, we will conduct studies on gonadotropes treated with estrogen in a range of paradigms. The information will be valuable in understanding normal reproduction, but will also form the basis of further studies to investigate the effects of drugs that affect estrogen action and environmental estrogens. Read moreRead less
Evolution of nervous system patterning processes: characterisation of homologs of key Drosophila regulatory genes from the coral Acropora. Defining the common mechanisms of nervous system development is one of the major goals of modern biology, but is presently being addressed largely by comparisons between a few very advanced (and therefore specialised) animals. Comparative data from a lower animal is urgently needed, and will clarify many aspects of nervous system evolution and development. Th ....Evolution of nervous system patterning processes: characterisation of homologs of key Drosophila regulatory genes from the coral Acropora. Defining the common mechanisms of nervous system development is one of the major goals of modern biology, but is presently being addressed largely by comparisons between a few very advanced (and therefore specialised) animals. Comparative data from a lower animal is urgently needed, and will clarify many aspects of nervous system evolution and development. The pioneering work carried out on Acropora in this laboratory suggests that it is perhaps the best choice currently available for this purpose. This project will use Acropora to address fundamental questions about the evolution of nervous system developmental processes.Read moreRead less
Sustaining neuronal communication through bulk endocytosis. Brain activities such as learning and memory rely on the ability of neurons to communicate. This research will improve our understanding of how synaptic vesicles recycle during periods of intense synaptic activity. This is a fundamental process relevant to neuronal communication, insulin release, hormone secretion, and allergic responses in health and disease and therefore has broad significance. This work will enhance Australia's exist ....Sustaining neuronal communication through bulk endocytosis. Brain activities such as learning and memory rely on the ability of neurons to communicate. This research will improve our understanding of how synaptic vesicles recycle during periods of intense synaptic activity. This is a fundamental process relevant to neuronal communication, insulin release, hormone secretion, and allergic responses in health and disease and therefore has broad significance. This work will enhance Australia's existing strength in cell biology and neuroscience and provide high quality training for an undergraduate student and post-doctoral scientist.Read moreRead less
Depression and Diabetes: Prevalence, diagnosis and help-seeking: Influence on depression, glycemic control and quality of life. Depression has been reported to be twice as prevalent and more persistent in individuals with diabetes than in the general population. The current research will investigate the point-prevalence of depression in a large sample of Australian diabetic outpatients using a case-finding instrument (CES-D) and follow-up structured clinical interview where appropriate. Demogr ....Depression and Diabetes: Prevalence, diagnosis and help-seeking: Influence on depression, glycemic control and quality of life. Depression has been reported to be twice as prevalent and more persistent in individuals with diabetes than in the general population. The current research will investigate the point-prevalence of depression in a large sample of Australian diabetic outpatients using a case-finding instrument (CES-D) and follow-up structured clinical interview where appropriate. Demographic, medical, and psychological correlates of depressiono will be investigated. The effects of the screening procedure and diagnosis on help-seeking behaviour, course of the depression, self-care, and glycemic control as well as qualtiy of life will be evaluated after six months.Read moreRead less
The function of menin in mammalian development. This project aims to determine the role of a ubiquitous transcriptional co-regulator, menin, in mammalian development. Mice that lack menin through targeted deletion of the gene die during embryogenesis, but the cause is unknown, although is likely to be due to the abnormal expression of genes usually regulated by this factor. We will determine which genes are inappropriately expressed and responsible for the accompanying developmental defects. Thi ....The function of menin in mammalian development. This project aims to determine the role of a ubiquitous transcriptional co-regulator, menin, in mammalian development. Mice that lack menin through targeted deletion of the gene die during embryogenesis, but the cause is unknown, although is likely to be due to the abnormal expression of genes usually regulated by this factor. We will determine which genes are inappropriately expressed and responsible for the accompanying developmental defects. This knowledge will help us understand the process of development in mammals, including birth defects in humans.Read moreRead less
Understanding and regulating autoimmune disease through the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) family transcription factor, v-rel reticuloendotheliosis viral oncogene homolog B (RelB). This program is well-aligned with the national research priority: Promoting and Maintaining Good Health. The disabling conditions rheumatoid arthritis and type 1 diabetes affect over 1% of Australia's population. They are incurable, so disability and the need for treatment p ....Understanding and regulating autoimmune disease through the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) family transcription factor, v-rel reticuloendotheliosis viral oncogene homolog B (RelB). This program is well-aligned with the national research priority: Promoting and Maintaining Good Health. The disabling conditions rheumatoid arthritis and type 1 diabetes affect over 1% of Australia's population. They are incurable, so disability and the need for treatment persist into old age and life expectancy is reduced. The program focuses on more effective and safer treatment, and future disease prevention, with immune therapy. This will have social and economic benefits to Australia. The research will advance Australia's intellectual leadership in Immunology, providing research training and career opportunities, and will lead to strong collaborations between basic scientists, clinicians and industry.Read moreRead less
Investigating Post-transcriptional Gene Regulation In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
In this program, I will enhance our understanding of cancer gene regulation and provide novel avenues for the treatment of aggressive tumours. Using own data and that from collaborators, I will determine patterns of gene regulation in blood cancers and identify markers that predict disease outcome. I aim to understand how gene regulation can transform healthy cells into tumour cells and whether personalised treatment can kill tumour cells more effectively and prevent relapse and metastasis.
Macrophage Polarisation And Control Of Pulmonary Inflammation.
Funder
National Health and Medical Research Council
Funding Amount
$895,494.00
Summary
As key immune cells, macrophages are polarised to phenotypes that turn inflammation on or off. In cystic fibrosis, defective macrophage polarisation enhances inflammation and prevents lung repair. We are defining the molecules and cellular pathways that control this process and identifying targets for existing drugs that can be used to reprogram macrophages and restore lung repair to improve patient outcomes.