Wheat Proteins, The Duodenal Microbiome And Immune Activation In The Aetiopathogenesis Of Non-coeliac Gluten Sensitivity And Functional Dyspepsia
Funder
National Health and Medical Research Council
Funding Amount
$1,997,150.00
Summary
Functional dyspepsia, characterised by troublesome pain in the upper abdomen, or an inability to finish a regular sized meal, is common, affecting up to 15% of Australians. There are no effective treatments. This project will evaluate the role of diet, in particular wheat, as a driver of the subtle inflammation and disturbances in the microbiome seen in the small intestine of functional dyspepsia patients, and test whether a gluten or wheat free diet is an effective treatment option.
Crohn’s disease (CD), an inflammatory disorder of the gut, is thought to result from an inappropriate response to an environmental trigger, likely gut bacteria. This project will assess differences in microbial communities and host gene expression of early- and late-stage CD tissues. A greater understanding of the differences in mucosal gene expression induced by specific bacteria may provide insights into the pathophysiology of CD, and could conceivably guide therapeutic choices in the future.
Construction And Immunogenic Evaluation Of Recombinant HBsAg-S Virus-like Particles Containing B And T Cell Epitopes Of
Funder
National Health and Medical Research Council
Funding Amount
$170,000.00
Summary
Helicobacter pylori is a significant human pathogen impacting on the health and well being of not only thousands of Australians, but also millions of people world-wide. However, the task of developing a vaccine against H. pylori remains important. Vaccination is the most effective mechanism to prevent disease associated with this infection, particularly gastric cancer, one of the most common causes of cancer death world-wide. However, current attempts to develop an effective vaccine for humans h ....Helicobacter pylori is a significant human pathogen impacting on the health and well being of not only thousands of Australians, but also millions of people world-wide. However, the task of developing a vaccine against H. pylori remains important. Vaccination is the most effective mechanism to prevent disease associated with this infection, particularly gastric cancer, one of the most common causes of cancer death world-wide. However, current attempts to develop an effective vaccine for humans has been limited by the non-availability of an effective and safe adjuvant. The aim is to construct a recombinant Virus-Like Particle which can be used as a safe and effective vaccine against Helicobacter pylori infections. We specifically aim to: · determine the most efficacious singular or combinatorial route-s of delivery of Virus-Like Particles (VLPs) which will induce the desired Th2 and B cell responses in mice · define the Th2 and B cell epitopes of H.pylori Kat A carboxyl terminus that can be used to construct chimeric HBsAg-S-Kat A VLPs · determine if the induction of desired immunological responses in mice are protective against wild type challengeRead moreRead less
Haemolysins And Haemoglobinases As Anti-hookworm Vaccines.
Funder
National Health and Medical Research Council
Funding Amount
$322,951.00
Summary
To meet its growth and reproductive requirements, hookworms must be able to utilise host haemoglobin located in the red blood cells. To puncture the red blood cell membrane, and break down the exposed haemoglobin into small peptides or single amino acids; the hookworm uses proteases called haemolysins and haemoglobinases. Identifying these proteases and disrupting their function may lead to reduced worm burdens, size and fecundity. Therefore these proteases could be ideal vaccine candidates.
CCR9 Expressing T Helper Cells In Immunity And Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
We have identified a unique subset of immune cells in autoimmune lesions named Tccr9 cells. You find these cells in the gut, but when the body shifts into disease mode, Tccr9 cells disseminate to the accessory organs of the digestive system. Understanding the relationship between gut Tccr9 cells and the Tccr9 cells that contribute to chronic inflammation and autoimmunity is the focus of this research proposal.
Interleukin 37 – A Novel Cytokine Therapy For Necrotizing Enterocolitis In The Preterm
Funder
National Health and Medical Research Council
Funding Amount
$748,848.00
Summary
Neonatologists are adept at keeping extremely premature babies alive. But the price is a rising incidence of life-threatening diseases that include necrotising enterocolitis (NEC), a progressive and destructive intestinal inflammation that may require surgery, after which just 30% survive. We have created highly potent variants of the anti-inflammatory molecule interleukin 37 whose actions will improve our understanding of NEC pathogenesis and reveal their therapeutic potential in NEC.
Diet And The Gut Microbiota As The Basis For Food Allergies
Funder
National Health and Medical Research Council
Funding Amount
$669,091.00
Summary
Diet and the composition of the gut microbiota represent new avenues to prevent or treat human diseases. We propose that allergies in western countries result from altered gut homeostasis. This application seeks to understand all the molecules involved, and to discover new bacteria that associate with, or protect from allergies.
The development of protective immunity is essential to fight infection. This depends on a small number of master regulatory transcription factors that drive the differentiation of precursor cells into mature immune cells such as NK, T and dendritic cells. This proposal will provide a fundamental advance in our understanding of immune cells and impact strategies aimed at the prevention and treatment of pathogen infections.
Immune Regulation, Cellular Trafficking And Chemokine Receptors In Intestinal Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$204,750.00
Summary
The intestine is exposed to a vast array of foreign substances, or antigens, from food to the abundant bacteria that populate the gut. The gut immune system has developed elaborate and poorly understood mechanisms for preventing inflammation in response to these antigens. A breakdown in these control mechanisms may be partly responsible for the chronic intestinal diseases known as inflammatory bowel diseases, which cause abdominal pain, diarrhoea and bleeding. A recently described immune cell ty ....The intestine is exposed to a vast array of foreign substances, or antigens, from food to the abundant bacteria that populate the gut. The gut immune system has developed elaborate and poorly understood mechanisms for preventing inflammation in response to these antigens. A breakdown in these control mechanisms may be partly responsible for the chronic intestinal diseases known as inflammatory bowel diseases, which cause abdominal pain, diarrhoea and bleeding. A recently described immune cell type, known as a regulatory T cell (T reg), is a powerful candidate cell as a master controller of intestinal inflammation. We know that T cells move to various sites in the body under the influence of hormone-like proteins known as chemokines, but the existence of T reg cells in the intestine, their characteristics, their behaviour and their specific response to chemokines, are all unknown. These studies aim to examine the presence and nature of T reg cells in human and mouse intestine, in both health and inflammation, and to explore how these cells migrate into the gut under the influence of chemokines. This knowledge will help in our understanding of intestinal immunity and endogenous regulation of immune responses, and will provide new targets for treatment of inflammatory bowel disease, and potentially other inflammatory diseases.Read moreRead less