Electrical activity in early enteric neuron development. Intestinal movements and secretion are critical to the good health and nutrition of both humans and animals. These functions are regulated by a large nervous system contained within the intestinal wall, the enteric nervous system. This project will identify how enteric nerve cells develop and how their behaviour influences the development of other enteric nerve cells. This is will provide an important base for more applied research aime ....Electrical activity in early enteric neuron development. Intestinal movements and secretion are critical to the good health and nutrition of both humans and animals. These functions are regulated by a large nervous system contained within the intestinal wall, the enteric nervous system. This project will identify how enteric nerve cells develop and how their behaviour influences the development of other enteric nerve cells. This is will provide an important base for more applied research aimed at developing treatments for diseases like chronic constipation and irritable bowel syndrome. It will also contribute to the growing knowledge about how epigenetic factors can modify genetically programmed development within the nervous system.Read moreRead less
Cell cycle and enteric neuron and glial differentiation. Enteric neurons arise from a very small starting population of precursor (neural crest) cells, most of which emigrate from the hindbrain, and colonise the developing gut. Over a protracted period of time the precursors proliferate and differentiate into glia and many different types of neurons. Cell cycle exit is a critical event in the development of many neuron types, largely because the time at which cells exit from the cell cycle lim ....Cell cycle and enteric neuron and glial differentiation. Enteric neurons arise from a very small starting population of precursor (neural crest) cells, most of which emigrate from the hindbrain, and colonise the developing gut. Over a protracted period of time the precursors proliferate and differentiate into glia and many different types of neurons. Cell cycle exit is a critical event in the development of many neuron types, largely because the time at which cells exit from the cell cycle limits the number of neurons that will be generated. We will determine whether exit from the cell cycle contributes to the differentiation and specification of enteric neurons and glia.Read moreRead less
Role of Histone deacetylase 3 (HDAC3) in intestinal epithelial cell homeostasis and tumorigenesis. Colon cancer is the most common cancer that affects men and women in Australia. Annually, in Victoria alone, more than 3400 people are diagnosed with colon cancer. Colon cancer arises through the accumulation of mutations in key genes over time. Identification of cancer causing genes provides the basis for the design of new cancer therapies. We recently identified a gene called Histone deacetylase ....Role of Histone deacetylase 3 (HDAC3) in intestinal epithelial cell homeostasis and tumorigenesis. Colon cancer is the most common cancer that affects men and women in Australia. Annually, in Victoria alone, more than 3400 people are diagnosed with colon cancer. Colon cancer arises through the accumulation of mutations in key genes over time. Identification of cancer causing genes provides the basis for the design of new cancer therapies. We recently identified a gene called Histone deacetylase 3 (HDAC3) as potentially involved in promoting colon cancer. The current proposal will now extend and validate this finding in mice. Importantly, drugs which inhibit HDAC3 have recently been developed for the treatment of cutaneous T-cell lymphoma. Defining the role HDAC3 plays in colon cancer will justify testing these drugs in colon cancer patients.Read moreRead less
Molecular signals that regulate the regenerative properties of intestinal epithelial cells. Most cancer deaths are due to the cancer spreading to other organs. Cancer is much more difficult to treat once it has spread to other organs in the body where the cancer cells can exist in a dormant state. Dormant cancer cells evade conventional anticancer treatment and can remain dormant for a very long time before they change back to a 'tumour-growing' state. An understanding of how the cancer initiati ....Molecular signals that regulate the regenerative properties of intestinal epithelial cells. Most cancer deaths are due to the cancer spreading to other organs. Cancer is much more difficult to treat once it has spread to other organs in the body where the cancer cells can exist in a dormant state. Dormant cancer cells evade conventional anticancer treatment and can remain dormant for a very long time before they change back to a 'tumour-growing' state. An understanding of how the cancer initiating (stem cell) property of tumour cells is maintained offers potential novel avenues to eliminate persistent cancer cells. This knowledge will ultimately lead to better management and treatment of cancer, and increase survival. An understanding of stem cell behaviour is also central to the control of degenerative conditions.Read moreRead less
The role of retinoic acid signalling in the development of the oesophageal epithelium. Oesophageal adenocarcinoma (OAC) is a disease with increasing incidence. The majority of patients with OAC are diagnosed when the cancer is at a late stage and therefore treatment options are limited, meaning the disease is almost invariably fatal. OAC arises from the precancerous condition, Barrett's oesophagus, which occurs as a consequence of chronic reflux, although the key processes driving its developmen ....The role of retinoic acid signalling in the development of the oesophageal epithelium. Oesophageal adenocarcinoma (OAC) is a disease with increasing incidence. The majority of patients with OAC are diagnosed when the cancer is at a late stage and therefore treatment options are limited, meaning the disease is almost invariably fatal. OAC arises from the precancerous condition, Barrett's oesophagus, which occurs as a consequence of chronic reflux, although the key processes driving its development are unknown. This project aims to better understand the critical first step in the progression to cancer and thus expand the scope for the development of therapies, particularly those aimed at early intervention, and tools that predict progression.Read moreRead less
The role of virulence factors of Clostridium difficile in food animals. Disease caused by the bacterium Clostridium difficile are a significant food production animal and public health problem in many countries. Specific animal and human public health resources have been allocated in many countries in efforts to mitigate the growing epidemics. The study proposed in this application presents a significant opportunity to learn about the virulence factors of animal strains of this bacterium about w ....The role of virulence factors of Clostridium difficile in food animals. Disease caused by the bacterium Clostridium difficile are a significant food production animal and public health problem in many countries. Specific animal and human public health resources have been allocated in many countries in efforts to mitigate the growing epidemics. The study proposed in this application presents a significant opportunity to learn about the virulence factors of animal strains of this bacterium about which very little is known. This project will lead to rationally designed preventative and treatment strategies that apply to both animals and humans, thereby impeding epidemics caused by C. difficile in Australia.Read moreRead less
Fundamental theoretical and experimental investigation of cartilage mechanics. Arthritis and chronic joint symptoms are one of the leading causes of disability in the community, yet a fundamental understanding of joint mechanics has yet to be realised. The aim of this project is to develop a new state-of-the-art mathematical model describing cartilage behaviour in humans. The model will explain how activities like walking maintain healthy cartilage by transferring growth factors through the tiss ....Fundamental theoretical and experimental investigation of cartilage mechanics. Arthritis and chronic joint symptoms are one of the leading causes of disability in the community, yet a fundamental understanding of joint mechanics has yet to be realised. The aim of this project is to develop a new state-of-the-art mathematical model describing cartilage behaviour in humans. The model will explain how activities like walking maintain healthy cartilage by transferring growth factors through the tissue, and quantitatively explain how wear is minimised in cartilage through weeping lubrication. This model will progress our understanding of cartilage mechanics in health and disease, and so help Australians age well and productively.Read moreRead less
Reg growth factors in gastric regeneration and disease. This project will obtain a more detailed knowledge of the role that growth factors play in helping the lining of the stomach repair itself after damage caused by disease. Growth factors may also play a role in causing stomach cancer. To do this we will examine the expression of growth factors in number of stomach diseases and cancer and assay the ability of growth factors to promote the growth of stomach cells.
This work is that it will co ....Reg growth factors in gastric regeneration and disease. This project will obtain a more detailed knowledge of the role that growth factors play in helping the lining of the stomach repair itself after damage caused by disease. Growth factors may also play a role in causing stomach cancer. To do this we will examine the expression of growth factors in number of stomach diseases and cancer and assay the ability of growth factors to promote the growth of stomach cells.
This work is that it will contribute to our knowledge of how cell growth in the stomach is controlled under normal circumstances and in the very common pathological conditions of tissue damage, inflammation and cancer. It may also help us understand how inflammation can in some circumstances lead to cancer.Read moreRead less
New genes and models for inflammatory bowel disease. Inflammatory bowel disease affecting millions of people world-wide and results in a significant economic burden ($100M in Australia per year). In collaboration with Australia’s largest biotechnology company, CSL, we will use a novel approach to discover the causes of inflammatory bowel disease. This work will lead to the development of new animal models of inflammatory bowel disease that are vital for analysing the disease and testing treatmen ....New genes and models for inflammatory bowel disease. Inflammatory bowel disease affecting millions of people world-wide and results in a significant economic burden ($100M in Australia per year). In collaboration with Australia’s largest biotechnology company, CSL, we will use a novel approach to discover the causes of inflammatory bowel disease. This work will lead to the development of new animal models of inflammatory bowel disease that are vital for analysing the disease and testing treatment options. In addition, this work may lead to new approaches to treating this disease. The project will result in a greater understanding of inflammatory bowel disease, the training of highly skilled scientists and potentially lead to economically valuable knowledge.Read moreRead less
Natural Therapeutic Products from Shark Bile. Scymnol and its sulfate are natural therapeutic products from shark bile with highly potent anti-oxidant and liver-protective activities. The Industry Partner and Macrides have co-patented the synthesis of scymnol to avoid using scarce natural resources. However, unresolved problems in scale-up of production have prevented them from supplying the growing demands of cosmetic and health food companies. Our research group has recently developed a potent ....Natural Therapeutic Products from Shark Bile. Scymnol and its sulfate are natural therapeutic products from shark bile with highly potent anti-oxidant and liver-protective activities. The Industry Partner and Macrides have co-patented the synthesis of scymnol to avoid using scarce natural resources. However, unresolved problems in scale-up of production have prevented them from supplying the growing demands of cosmetic and health food companies. Our research group has recently developed a potential synthetic route for scymnol sulfate. The present project aims to develop a commercially-viable scale-up of this synthesis for manufacturing scymnol and scymnol sulfate to solve current supply problems; and to provide essential safety information for their appropriate use; and evaluate potential new therapeutic uses.Read moreRead less