Molecular Profiling Of Breast Tumour Stem/Progenitor Cells
Funder
National Health and Medical Research Council
Funding Amount
$308,824.00
Summary
Breast cancer is the commonest cancer in women in many countries including Australia, the USA and the UK. The incidence of breast cancer has been increasing over the last decade however mortality from breast cancer has declined. Although there is debate as to the exact reasons for this decline in mortality, it is clear that the introduction of the screening program as well as improvements in treatment have played a significant role. Nevertheless, a proportion of patients will have disseminated d ....Breast cancer is the commonest cancer in women in many countries including Australia, the USA and the UK. The incidence of breast cancer has been increasing over the last decade however mortality from breast cancer has declined. Although there is debate as to the exact reasons for this decline in mortality, it is clear that the introduction of the screening program as well as improvements in treatment have played a significant role. Nevertheless, a proportion of patients will have disseminated disease at presentation and may not fully respond to treatment. In addition a number of patients will go on to form apparent recurrence of the primary tumour and- or distant metastases following what appears to be complete clearance of a tumour. In recent years a new concept has been put forward that might account for some of these recurrences. It is thought that the cells in a tumour do not all divide at the same rate. Instead some cells only divide rarely, and then give rise to other cells which divide rapidly and form the bulk of the tumour. Since these 'tumour stem cells' are slow cycling they will be resistant to existing chemotherapy because this affects rapidly dividing cells. These resistant cells may then go on to form another tumour. We intend to study these 'tumour stem cells' using a range of techniques that will show us how they differ from both the rest of the tumour cells and the different types of normal cells in the breast. By identifying molecules that are different in the tumour stem cells we will then have new targets for therapies that are designed to target these chemotherapy-resistant cells. Such therapies could be used in the future in conjunction with existing therapies to achieve a greater eradication of breast tumours.Read moreRead less
Functional Validation Of FoxP3 Target Genes In Human Regulatory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$545,341.00
Summary
Using DNA based technologies we have focused on rare white blood cells known as regulatory T cells. These cells are policeman of the immune system and are responsible for maintaining balanced immune reactions, and preventing attack against harmless substances. These cells prevent autoimmune disease in healthy individuals, and only by first understanding how they work normally can we investigate and correct the defects in autoimmune diseases such as type 1 diabetes.
Novel Approaches To Nanomedicines For Future Therapies
Funder
National Health and Medical Research Council
Funding Amount
$2,414,215.00
Summary
Nanomedicines have the potential to transform healthcare by targeting significant health issues such as Alzheimer’s, diabetes and Parkinson’s diseases that have mainly eluded successful therapeutic solutions. In addition, nanotechnology has the potential to significantly improve the treatment of chronic pain by repurposing analgesic medications for improved effectiveness without significant side effects. I will target these two areas of research during the next five years.
L1 Retrotransposition: The Missing Link Between Genetics And Environmental Factors In Parkinson's Disease ?
Funder
National Health and Medical Research Council
Funding Amount
$604,644.00
Summary
The study proposed here focuses on understanding the role of specific mobile DNA sequences in the interaction between environmental and genetic risk factors causing Parkinson’s disease (PD) leading to dementia. The project proposes identification of mobile DNA induced mutations in post-mortem human PD patient brain samples. The significance and mechanisms of mobile DNA induced mutations will be then tested in a PD mouse model.
Defining The Changes In Cell Biology Caused By PRESENILIN Truncations Associated With Different Diseases
Funder
National Health and Medical Research Council
Funding Amount
$622,886.00
Summary
Truncations of the PRESENILIN genes in humans can cause two very different diseases: inherited, early onset Alzheimer’s disease (familial Alzheimer's disease) and a skin disease named inherited Acne Inversa. One truncation is also involved in the non-inherited, late onset form of Alzheimer’s disease. Why do these different truncations produce different diseases? Investigating this question will teach us more about the molecular bases of these different diseases. This understanding will be requir ....Truncations of the PRESENILIN genes in humans can cause two very different diseases: inherited, early onset Alzheimer’s disease (familial Alzheimer's disease) and a skin disease named inherited Acne Inversa. One truncation is also involved in the non-inherited, late onset form of Alzheimer’s disease. Why do these different truncations produce different diseases? Investigating this question will teach us more about the molecular bases of these different diseases. This understanding will be required for the development of treatments.Read moreRead less
Translational Control Of Gene Expression And The Choice Between Cell Death And Proliferation
Funder
National Health and Medical Research Council
Funding Amount
$378,000.00
Summary
Proteins carry out most enzymatic and structural functions in a cell. Thus, the kinds of protein molecules that are found in a given cell determine its characteristics and cells respond to changes in their environment by adjusting the abundance of some or many proteins in their collection. The instructions for the assembly of proteins are encoded in the genes and this information is expressed via intermediary molecules called messenger (m)RNA. Both, transcription of the genes into mRNA molecules ....Proteins carry out most enzymatic and structural functions in a cell. Thus, the kinds of protein molecules that are found in a given cell determine its characteristics and cells respond to changes in their environment by adjusting the abundance of some or many proteins in their collection. The instructions for the assembly of proteins are encoded in the genes and this information is expressed via intermediary molecules called messenger (m)RNA. Both, transcription of the genes into mRNA molecules and their subsequent translation by the ribosomes into protein are tightly controlled steps in the gene expression pathway. Erroneous gene expression is a major factor in human disease and dysregulation of translation is linked to a growing spectrum of illnesses such as cancer and cardiovascular disease, viral infection, and less frequent hereditary syndromes. The project proposed here is prompted by emerging evidence for a role of translational regulation in controlling the balance between cell death and survival. Tipping this balance has disastrous consequences for an organism as evidenced by its involvement in many major disorders (e. g. stroke, heart failure, neurodegeneration, AIDS, cancer, autoimmunity). Our aim is to test the hypothesis that a putative translational regulator termed p97-DAP5-NAT1, and a specialised mechanism of translation initiation by internal ribosome entry are important for the maintenance of this balance. To investigate this, we will employ DNA chips, a novel tool from Genomics research that allows the measurement of the levels of thousands of mRNA molecules in a single experiment. It is conceivable that knowledge of these special mechanisms of translation will lead to novel targets for therapeutic intervention, and this work will contribute some of the experimental tools to explore these avenues in the future.Read moreRead less
Genome-wide SNP Analysis Of Fibroblasts Juxtaposed Or Distant From Epithelial Breast And Ovarian Tumours
Funder
National Health and Medical Research Council
Funding Amount
$401,763.00
Summary
In the past it was believed that the driving factor in the process of cancer devlopment was the cancer tissue itself. More recently however, it has become clear that the process is far more complex and that many aspects of human biology can profoundly influence both an individuals presiposition to cancer and the severity of disease. Many laboratories, including our own, have shown that gene mutations frequently occur in cancer tissue but recent studies have suggested that the apparently normal t ....In the past it was believed that the driving factor in the process of cancer devlopment was the cancer tissue itself. More recently however, it has become clear that the process is far more complex and that many aspects of human biology can profoundly influence both an individuals presiposition to cancer and the severity of disease. Many laboratories, including our own, have shown that gene mutations frequently occur in cancer tissue but recent studies have suggested that the apparently normal tissue surrounding the cancer (often referred to stroma) may also contain mutations. This so called 'cancer associated stroma'(CAS) is also thought to harbour genetic mutations and some studies have shown that without these mutations the cancer cannot survive. At present we have only had glimpses of the genetic alterations that may occur in CAS and there is an urgent need to fully understand the interplay between CAS and frankly cancerous tissue. Our laboratory will utilise high density, genome-wide screening technologies to search for novel mutations in CAS from breast and ovarian cancers. A complete understanding of the role stroma plays in cancer development is likely to lead to novel ways of treating and preventing cancer. Consequently, the identification of the full repertoire of stroma-derived cancer promoting genes is emerging as one of the most important areas in cancer research. The identification of these genes could lead to the development of novel diagnostic markers for use in cancer detection, diagnosis and-or prognosis.Read moreRead less
Functional Assessment Of Bioenergetic Defects In Hereditary Spastic Paraplegia
Funder
National Health and Medical Research Council
Funding Amount
$113,322.00
Summary
Hereditary spastic paraplegia (HSP) is a degenerative, hereditary disorder which affects the legs. Currently there are no treatments that target the disease process. We seek to identify the genes responsible for this condition in a group of Australian patients. Cell samples obtained from these patients will be tested for energy defects. We hope to improve our understanding of the underlying disease processes in order to find new ways to prevent, treat and cure this condition.
Developing Species-specific, Structure-targeting Peptides As A Novel Class Of Antibiotics
Funder
National Health and Medical Research Council
Funding Amount
$607,967.00
Summary
Multidrug, antibiotic resistance is a serious global threat. It is a real possibility that in the absence of new antibiotics, common infections could soon become untreatable. This project will develop a novel class of antibiotics that target the core structures of essential bacterial proteins. The successful outcome of this work will also aid the development of specific peptide-based inhibitors for numerous additional diseases, including viral and fungal infections and cancer.