The migration of cancer cells (metastasis) is responsible for most cancer deaths. Central to this is dynamic organisation of the actin cytoskeleton _ an internal structure that provides cell shape and enables movement. We have identified a family of small molecules (called miR-200) that regulates this actin cytoskeleton through specifically downregulating various genes. We are investigating the nature of these genes and their role in cell motility _ an underlying pre-requisite of metastasis.
How Intestinal Motility Activates Sensory Pathways
Funder
National Health and Medical Research Council
Funding Amount
$555,875.00
Summary
Pain and discomfort from the gut are common and unpleasant. We understand how gut sensory nerve cells work, at the cellular, molecular and genetic level. However, movement of the gut wall and contents are the major cause of activation of sensory neurons. We know little about which particular patterns of movement cause pain. This is crucial information for accurately diagnosing human gut disorders, for monitoring effectiveness of treatments and for identifying potential new drug targets.
Mechanical Factors In Normal Human Colonic Motility
Funder
National Health and Medical Research Council
Funding Amount
$650,023.00
Summary
Abnormal human colonic contractions cause significant medical, societal and financial burdens. Diagnosis and treatment of motility disorders requires an understanding of normal colonic contractility against which to measure dysfunction. Through state-of-the-art recording and analytical techniques, developed by the applicants, this project will provide the first clear description of normal human colonic motor patterns and how they are generated.
Glucose is a critical fuel for living organisms and its presence in the gut triggers nerves that slow stomach emptying. However, little is known of how glucose is actually detected in the gut. We have established that sweet taste molecules of the tongue are also present in the gut, where they may detect glucose. This research will measure the expression and function of these molecules in the gut of humans and mice, and reveal key information on their potential as targets in health and disease.
Stimulant laxatives are widely used and usually very effective in the short term, but how they work is very poorly understood. Our recent work has shown that they selectively excite sensory pathways from the colon which then trigger defaecation. This points to an undiscovered mechanism that potently affects colonic sensation and motility. This is likely to be a target for new treatments for other colonic disorders such as Irritable bowel syndrome and faecal incontinence.
Understanding The Role Of The Atypical Cadherin Fat4 In Lymphatic Vascular Development
Funder
National Health and Medical Research Council
Funding Amount
$1,006,248.00
Summary
This application will define the role of a large cell adhesion molecule, FAT4, in lymphatic vascular development. By understanding how FAT4 functions in lymphatic vessels, we will gain insight to the mechanisms by which mutations in the gene that encodes this protein cause a human lymphoedema syndrome.
Use of mitochondrial electron transport chain mutants to evaluate how non-phosphorylating respiration influences plant metabolite profiles and stress tolerance. This project uses transgenic plant technology to elucidate how mitochondrial function impacts on the profile of metabolites in plant cell and tissues and whether altering these profiles influences a plant's ability tog row in harsh conditions. It will contribute to our fundamental knowledge of plant metabolism using a metabolomic anaylsi ....Use of mitochondrial electron transport chain mutants to evaluate how non-phosphorylating respiration influences plant metabolite profiles and stress tolerance. This project uses transgenic plant technology to elucidate how mitochondrial function impacts on the profile of metabolites in plant cell and tissues and whether altering these profiles influences a plant's ability tog row in harsh conditions. It will contribute to our fundamental knowledge of plant metabolism using a metabolomic anaylsis of plant stress response. This will be achieved using new high-throughput technologies, allowing reliable qualitative and quantitative analysis of large numbers of samples. This approach will compliment existing genomic and proteomic analyses of plants exposed to abiotic stress.Read moreRead less
Target Of Rapamycin control of nutrient uptake. This project aims to study nutrient uptake in eukaryotes. It is expected to generate new knowledge of critical and conserved features of environmental and Target Of Rapamycin (TOR)-mediated control of nutrient uptake, specifically endocytosis, building on novel preliminary data that identifies novel TOR control points. The expected outcomes include new insights into mechanisms controlling nutrient uptake and fostering institutional collaboration. T ....Target Of Rapamycin control of nutrient uptake. This project aims to study nutrient uptake in eukaryotes. It is expected to generate new knowledge of critical and conserved features of environmental and Target Of Rapamycin (TOR)-mediated control of nutrient uptake, specifically endocytosis, building on novel preliminary data that identifies novel TOR control points. The expected outcomes include new insights into mechanisms controlling nutrient uptake and fostering institutional collaboration. This knowledge is highly relevant to any industry or research project utilising living organisms, as nutrient availability supports survival, cell growth and proliferation.Read moreRead less
Mechanisms Of Premature Cranial Fusion: Role Of Retinol Binding Protein 4 In Osteogenesis And Suture Fusion
Funder
National Health and Medical Research Council
Funding Amount
$555,855.00
Summary
Craniosynostosis is a condition where the skull bones fuse prematurely, affecting skull shape, vision and cognition. It occurs in 1 in 2,500 births. The only treatment is surgery, which is life-threatening, costly and may need to be repeated. By studying how fusion happens in this project we may be able to devise therapies to minimize the risks and need for re-operation. Here, we hope to show that modification of a single substance in the skull of mouse models can prevent premature bone fusion.
Mechanisms controlling enteroendocrine hormone secretion in human duodenum. This project aims to gain a deeper understanding of nutrient sensing pathways present in enteroendocrine cells within the human intestine. These cells control digestive function, blood glucose levels and food intake and are thus critical to digestion. This project will endeavour to be the first to assess the biology of human enteroendocrine cells and will use innovative approaches to deeply assess function from the level ....Mechanisms controlling enteroendocrine hormone secretion in human duodenum. This project aims to gain a deeper understanding of nutrient sensing pathways present in enteroendocrine cells within the human intestine. These cells control digestive function, blood glucose levels and food intake and are thus critical to digestion. This project will endeavour to be the first to assess the biology of human enteroendocrine cells and will use innovative approaches to deeply assess function from the level of the individual to isolated enteroendocrine cells.Read moreRead less