Migration And Differentiation Of Enteric Neuron Precursors
Funder
National Health and Medical Research Council
Funding Amount
$385,116.00
Summary
There are many millions of nerve cells within the wall of the intestine, and they control many intestinal functions, including motility. During development, these nerve cells arise from cells which migrate away from the developing brain and first enter the stomach. The migratory cells are called neural crest cells. After entering the stomach, neural crest cells migrate within the wall of the gastrointestinal tract, until they reach the far (anal) end. In embryonic mice, this colonisation of the ....There are many millions of nerve cells within the wall of the intestine, and they control many intestinal functions, including motility. During development, these nerve cells arise from cells which migrate away from the developing brain and first enter the stomach. The migratory cells are called neural crest cells. After entering the stomach, neural crest cells migrate within the wall of the gastrointestinal tract, until they reach the far (anal) end. In embryonic mice, this colonisation of the entire small and large intestines by neural crest cells takes over 4 days, and in humans the process probably takes at least one week. It is essential that the neural crest cells colonise the entire gastrointestinal tract, since regions of intestine lacking neural crest cells (and hence nerve cells) cannot function and intestinal contents build up in front of the region lacking nerve cells. This condition is found in some babies (Hirschsprung's disease), and it can only be treated by surgically removing the region lacking nerve cells. It is therefore essential that migratory neural crest cells colonise the entire gastrointestinal tract. Currently, little is known about the mechanisms controlling the migration of neural crest cells, and whether a) particular molecules within the gut wall are important for migration, and-or b) the migratory behaviour of the neural crest cells is regulated mostly by the neural crest cells themselves. In this study we will take time-lapse images of neural crest cells migrating through the gut of embryonic mice to identify the factors that are important for the migration. After the neural crest cells have colonised the entire intestine, they develop into different types of nerve cells. We will also examine some of the factors affecting the development of different types of nerve cells.Read moreRead less
Identification of novel antigens for vaccination and immunotherapy against the human gastric pathogen, Helicobacter pylori. The bacterium Helicobacter pylori is a significant human pathogen which infects the stomach where it is the major cause of stomach and duodenal ulcers, plus two types of cancer. This project proposes to utilise a novel strategy to identify potential vaccine targets on the bacterial surface with the aim to develop an effective vaccine against this organism. Such a vaccine wo ....Identification of novel antigens for vaccination and immunotherapy against the human gastric pathogen, Helicobacter pylori. The bacterium Helicobacter pylori is a significant human pathogen which infects the stomach where it is the major cause of stomach and duodenal ulcers, plus two types of cancer. This project proposes to utilise a novel strategy to identify potential vaccine targets on the bacterial surface with the aim to develop an effective vaccine against this organism. Such a vaccine would protect against the development of stomach cancer, hence saving lives, plus significantly reduce the incidence of stomach ulcers, thereby reducing suffering of individuals and providing financial benefits to employers.Read moreRead less
Defining how serotonin regulates gut motility. This project aims to deepen knowledge of gastrointestinal physiology, and reveal the mechanisms by which the major gastrointestinal signalling molecule, serotonin, regulates gut peristalsis. Almost all of the serotonin in our body is made in the gastrointestinal tract where it controls many functions, including how our gut wall contracts during peristalsis. Proper control of gut peristalsis and the transit of material through our bowel is important ....Defining how serotonin regulates gut motility. This project aims to deepen knowledge of gastrointestinal physiology, and reveal the mechanisms by which the major gastrointestinal signalling molecule, serotonin, regulates gut peristalsis. Almost all of the serotonin in our body is made in the gastrointestinal tract where it controls many functions, including how our gut wall contracts during peristalsis. Proper control of gut peristalsis and the transit of material through our bowel is important for our health. This project expects to define how serotonin controls peristalsis, where in the bowel this serotonin comes from, how serotonin communicates with the nervous system in our gastrointestinal tract, and how the cells that synthesise gut serotonin respond to contraction to trigger the secretion of serotonin.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
Barrett's oesophagus (BO) is a condition that arises in some patients with chronic reflux (heartburn) and increases the risk of developing cancer of the oesophagus. However, the exact mechanisms involved in its development are unknown. This project aims to investigate how a protein called sonic hedgehog might be involved using novel cell culturing techniques that allow us to model the growth of oesophageal tissue in the laboratory. This could lead to development of new therapies for treating BO.
Functions Of FZD7 In The Intestine And Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$644,761.00
Summary
Wnt proteins are a family of signaling molecules that are critical for the function of normal and cancerous epithelial cells in the gut. However, the cell surface receptor that transmits Wnt signals is not known. Our research strongly implicates one Wnt receptor (FZD7). Here we test this using innovative mouse and cell line models. We wish to understand how Wnt-driven processes are activated. This knowledge will lead to novel avenues to block aberrant activation of Wnt signalling in cancer cells
Discovery Early Career Researcher Award - Grant ID: DE180100261
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Understanding interactions between gut epithelial stem cells and neurons. This project aims to investigate the interaction between gut neurons and the epithelial stem cell compartment, as well as the relationship between age-related loss of enteric neurons and changes in gut epithelial stem cells. This project will include novel co-culturing of organoids and enteric neurospheres, which will identify mechanisms by which nerves influence the epithelia. The outcome of the project will be a better u ....Understanding interactions between gut epithelial stem cells and neurons. This project aims to investigate the interaction between gut neurons and the epithelial stem cell compartment, as well as the relationship between age-related loss of enteric neurons and changes in gut epithelial stem cells. This project will include novel co-culturing of organoids and enteric neurospheres, which will identify mechanisms by which nerves influence the epithelia. The outcome of the project will be a better understanding of the biology of the body’s most highly proliferative, long-lived stem cells, intestinal epithelial stem cells. This could have significant long term impact on the quality of life in an ageing population.Read moreRead less