The Role Of Stem-progenitor Cells In Regeneration Of Mouse Endometrium.
Funder
National Health and Medical Research Council
Funding Amount
$311,938.00
Summary
The endometrium (lining of the uterus) undergoes breakdown and re-growth each month as part of the menstrual cycle. This restorative process is not well understood. For the first time stem cells have been identified within human endometrium that are likely to be responsible for its remarkable regeneration. The aim of this project is to identify stem cells within the mouse endometrium, to use as a model to understand how the endometrium restores each month after menstruation.
We have discovered a single tumour factor which causes cancer cachexia, a wasting condition that is one of the worst complications of malignancy, for which there is no current effective treatment. We have developed antibodies which effectively block this condition in preclinical models and have produced human/humanised version of this. This application is to characterise these human antibodies to allow us proceed to clinical trials.
Central Neural Circuits Subserving Nutrient–activated Thermogenesis - The Basis Of Post Prandial Energy Expenditure
Funder
National Health and Medical Research Council
Funding Amount
$766,207.00
Summary
Studies of “energy burning” brown fat, including its importance in the determination of obesity in humans and the potential to increase its capacity by turning white fat into brown-like fat are currently foremost in obesity research. Here we study the detail of brain pathways that dictate brown fat activity after a meal resulting in the burning of ingested calories and reduction of body weight. The results will give us a better idea of how we can harness brown fat to combat obesity.
Genetic analysis of cohesin function and regulation in Drosophila. In yeast, a multiprotein complex, called cohesin, holds newly replicated chromatids together until the cell is ready to partition each chromatid into its daughter cells. We and others have shown that cohesins are regulated differently in animal cells. We propose to combine classical genetic analyses with two new and innovative techniques, time-lapse confocal microscopy of fluorescent proteins in living cells and gene-specific kno ....Genetic analysis of cohesin function and regulation in Drosophila. In yeast, a multiprotein complex, called cohesin, holds newly replicated chromatids together until the cell is ready to partition each chromatid into its daughter cells. We and others have shown that cohesins are regulated differently in animal cells. We propose to combine classical genetic analyses with two new and innovative techniques, time-lapse confocal microscopy of fluorescent proteins in living cells and gene-specific knockout techniques to study key cohesin regulators in Drosophila. These studies will provide us with novel insights into how multicellular organisms regulate the structure and stability of their chromosomes.Read moreRead less
The Cytochrome P450 Gene Super-family in Drosophila melanogaster; Gene Function and Insecticide Resistance. The cytochrome P450 (Cyp) gene super-family is represented by over 90 sequences in the genome of the vinegar fly, Drosophila melanogaster. To date, four Cyp genes are found to be involved in insecticide resistance. The function of the majority of Cyp genes is unknown. This project will investigate the function and regulation of D. melanogaster Cyp genes, linking the fly's genotype to its ....The Cytochrome P450 Gene Super-family in Drosophila melanogaster; Gene Function and Insecticide Resistance. The cytochrome P450 (Cyp) gene super-family is represented by over 90 sequences in the genome of the vinegar fly, Drosophila melanogaster. To date, four Cyp genes are found to be involved in insecticide resistance. The function of the majority of Cyp genes is unknown. This project will investigate the function and regulation of D. melanogaster Cyp genes, linking the fly's genotype to its phenotype. By studying the effects of Cyp genes on fly survival, Cyp gene expression and regulation, and expressing selected Cyp genes in a yeast expression system, we will enhance our understanding of Cyp gene function and evolution.Read moreRead less
Central Neural Regulation Of Brown Fat Function – Glucose Sensing And CNS Pathways
Funder
National Health and Medical Research Council
Funding Amount
$761,942.00
Summary
Our research aims to identify how specific brain cells detect changes in glucose levels and how ageing and diet affect their function. We identified a subset of nerve cells that detect changes in glucose and the “hunger” hormone ghrelin, their ability to do so adapting with age and nutritional status. This project will investigate the potential of these nerve cells as targets for therapeutic and diet- intervention strategies to target obesity, diabetes and promote healthy ageing.
Deadly Commute - Targeting The Trafficking Mechanisms That Licence Inflammatory Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$774,544.00
Summary
MLKL is a protein naturally found inside cells. MLKL is activated by inflammation. Once activated, MLKL relocates to the outer periphery of cells and kills them. Gut cells are especially vulnerable to death-by-MLKL and this problem causes Inflammatory Bowel Disease. Using cutting edge microscopy, we have discovered how MLKL moves to the periphery of cells prior to killing them. We will test if blocking this movement of MLKL to the cell periphery stops gut death and Inflammatory Bowel Disease.
Functional characterization of SSB2: a novel single-stranded DNA binding protein. Defects in the DNA damage response pathway underpin many human genetic disorders and diseases. A detailed understanding of this pathway has enormous implications for future medicine. The proposed research will lead to functional characterization of a new protein, identify new concepts in DNA damage repair pathways, train young researchers and place Australia among the leaders in this internationally significant and ....Functional characterization of SSB2: a novel single-stranded DNA binding protein. Defects in the DNA damage response pathway underpin many human genetic disorders and diseases. A detailed understanding of this pathway has enormous implications for future medicine. The proposed research will lead to functional characterization of a new protein, identify new concepts in DNA damage repair pathways, train young researchers and place Australia among the leaders in this internationally significant and highly competitive area of research. It will underpin the national research priority of Promoting and Maintaining Good Health and help Australia capitalise on a plethora of opportunities for future economic and health benefits.Read moreRead less
Novel roles for importin alpha proteins in the nucleus. The project will provide fundamental new information about how changes in cell function are influenced by importin (IMP) alpha proteins, both through changes in gene transcription and through alterations to intracellular transport. These findings will inform areas of national priority that include Aging Well, Aging Productively with specific regard to cellular stress responses, and A Healthy Start to Life in the context of production of hea ....Novel roles for importin alpha proteins in the nucleus. The project will provide fundamental new information about how changes in cell function are influenced by importin (IMP) alpha proteins, both through changes in gene transcription and through alterations to intracellular transport. These findings will inform areas of national priority that include Aging Well, Aging Productively with specific regard to cellular stress responses, and A Healthy Start to Life in the context of production of healthy, genetically intact sperm. This project draws together an international team to investigate a phenomenon with implications for new understanding of normal developmental processes and the response of cells/tissues to disease conditions.Read moreRead less
To study the genetic alterations that give rise to cancer. In particular, exploring how too little death of cells can lead to a tumour. If too few cells in a tissue die, a tumour may develop there. The team is exploring how the cell death process is normally controlled. They plan to characterise the molecules inside cells that determine whether a cell lives or dies and hope that better understanding of those molecules will help to explain how tumours arise. It could also lead to new drugs that c ....To study the genetic alterations that give rise to cancer. In particular, exploring how too little death of cells can lead to a tumour. If too few cells in a tissue die, a tumour may develop there. The team is exploring how the cell death process is normally controlled. They plan to characterise the molecules inside cells that determine whether a cell lives or dies and hope that better understanding of those molecules will help to explain how tumours arise. It could also lead to new drugs that can kill tumour cells more effectively by directly triggering the normal death switch of the cell.Read moreRead less