The Role Of SPARC In Intestinal Extracellular Matrix Changes And Carcinogenesis
Funder
National Health and Medical Research Council
Funding Amount
$526,728.00
Summary
The inflammatory bowel diseases (IBDs), Crohn s disease (CD) and ulcerative colitis (UC), are lifelong, chronic, incurable conditions and the number of patients being diagnosed with these conditions is increasing worldwide. Over recent years there has been the development of new treatments effective in controlling the chronic inflammation of the bowel in many of these patients. There is no evidence, however that these therapies reduce the rate of bowel scarring or the development of bowel cancer ....The inflammatory bowel diseases (IBDs), Crohn s disease (CD) and ulcerative colitis (UC), are lifelong, chronic, incurable conditions and the number of patients being diagnosed with these conditions is increasing worldwide. Over recent years there has been the development of new treatments effective in controlling the chronic inflammation of the bowel in many of these patients. There is no evidence, however that these therapies reduce the rate of bowel scarring or the development of bowel cancer that complicated these conditions. Healing of the bowel inflammation can result in scarring. Whether scarring develops or not hinges on the balance between tissue production and destruction. If production outstrips destruction then scarring may occur, but if this balance can be modified in favour of reduced production then, potentially, healing may proceed without scarring. This project aims to investigate the role of a protein, SPARC, that can regulate scar formation and its interactions with other proteins that can alter scar formation in a mouse model of chronic bowel inflammation. Chronic inflammation of the bowel can also cause the development of colon cancer. Colon cancer is one of the most common cancers in the Australian population. The level of SPARC in the colon cancer at time of initial surgery may predict the risk of disease recurrence. The aim of this study is to determine if SPARC levels can identify those patients at higher risk of cancer recurrence. The role of SPARC will also be examined in a mouse model of colon cancer to determine if increased SPARC levels increased or decrease the rate of cancer growth and its spread.Read moreRead less
Evolution And Function Of A Novel Lateral Flagellar Locus, Flag-2, In Pathogenic Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$465,158.00
Summary
This project will study how the bacteria that cause infant diarrhoea colonize the intestine and induce disease. We have identified a novel genetic region that allows E. coli to survive and persist in the intestine. Similar genes are also present in closely related organisms. This project will help us to undestand how new diseases evolve and emerge and may lead to the development of new vaccines to protect against infant diarrhoea.
Contribution Of Nuclear Targeting Of The NleE-OspZ Family Of Proteins To Escherichia Coli And Shigella Virulence
Funder
National Health and Medical Research Council
Funding Amount
$542,462.00
Summary
This project will study how the bacteria that cause infant diarrhoea colonize the intestine and induce disease. We have identified new bacterial proteins that allow E. coli to manipulate the normal host cell processes involved in killing an invading bacterium. Similar proteins are also present in the closely related organism, Shigella which causes dysentary. We will determine how these proteins act by finding the host cell proteins they bind.
The Role Of MicroRNAs As New Anti-inflammatory Targets For The Treatment Of Asthma
Funder
National Health and Medical Research Council
Funding Amount
$625,655.00
Summary
Asthma is a significant health and economic burden to our society and its prevalence has increased over the last 25 years. New ways of treating asthma are urgently required as current therapeutics treat the symptoms and not the cause of the disease. Asthma is widely thought to be due to the abnormal accumulation of white blood cells (inflammation) in the lungs of diseased individuals. In this project we are exploring new advanced ways to inhibit inflammation and the development of disease.
Galectin-3 And Phagocyte Function In Severe Asthma
Funder
National Health and Medical Research Council
Funding Amount
$698,084.00
Summary
Asthma, a major chronic inflammatory disease affects more than 2 million Australians. Neutrophilic severe asthma is not responsive to current therapies. We have recently made a significant advance in understanding neutrophilic asthma, reporting low levels of a protein called galectin-3 (gal-3). In this project we will explore the role of gal-3 its effect on the resolution of inflammation. This study will result significantly advance the knowledge of the mechanisms of neutrophilic severe asthma.
Therapeutic Potential Of The IL-3-IL-5-GM-CSF Common Beta Receptor To Treat Upper And Lower Allergic Airway
Funder
National Health and Medical Research Council
Funding Amount
$150,442.00
Summary
This research aims to develop new treatments for allergic diseases such as asthma and allergic rhinitis, which remain significant public health problems in Australia. We will develop new therapies with the potential to completely suppress acute and chronic allergic disease targeting a common receptor protein that controls multiple facets of allergic inflammation. We will test antibodies intended to treat human asthma using a novel mouse strain expressing the human form of this receptor.
Role Of IL-3 In Allergic Inflammation: Modulation Of Basophils, Mast Cells, Eosinophils And Remodelling In Asthma.
Funder
National Health and Medical Research Council
Funding Amount
$495,380.00
Summary
Asthma is an important disease in the Australian community. We will investigate how the underlying inflammation in this disease is controlled and will focus our studies on a hormone-like regulator of the immune system called interleukin-3. Our hypothesis is that interleukin-3 regulates basophils, mast cells and remodelling of the airways which are central features of asthma. This study will give a better understanding of how the inflammation is caused and information for new drug targets.
Novel Probiotics And Naturally-sourced Extracts As Treatment Strategies For Chemotherapy-induced
Funder
National Health and Medical Research Council
Funding Amount
$322,183.00
Summary
Intestinal mucositis is a serious disorder associated with chemotherapy treatment in cancer patients. Recently, a new strain of probiotic bacteria has been described with the potential to decrease the severity of intestinal mucositis. However, it is not known whether the live probiotic is necessary for this effect. We will compare the live probiotic, dead probiotic and factors sourced from this probiotic for the potential to decrease the severity of intestinal mucositis. Similarly, there have be ....Intestinal mucositis is a serious disorder associated with chemotherapy treatment in cancer patients. Recently, a new strain of probiotic bacteria has been described with the potential to decrease the severity of intestinal mucositis. However, it is not known whether the live probiotic is necessary for this effect. We will compare the live probiotic, dead probiotic and factors sourced from this probiotic for the potential to decrease the severity of intestinal mucositis. Similarly, there have been anecdotal claims of medicinal application for so-called ‘bioactive’ extracts and formulations derived from a range of mammalian, marine and plant sources. Specifically, Lyprinol (an extract derived from the New Zealand Green-Lipped Mussel), Emu Oil (derived from Emu meat) and the herbal extract Iberogast, have been reported to possess antiinflammatory properties. Indeed, these agents are used widely for the adjunctive relief of symptoms associated with arthritis and joint pain. However, these agents have yet to be tested for their potential to treat or prevent intestinal mucositis. For the first time, utilizing proven, controlled animal model systems, the current submission will explore the therapeutic potential of these agents, alone and in combination with indicated probiotics, for their capacity to treat or prevent mucositis. Should efficacy be demonstrated, a potential mechanism of action will be sought by investigating effects on intestinal stem cells.Read moreRead less
The Role Of MicroRNAs In The Regulation Of Antiviral And Inflammatory Responses During Experimental Rhinovirus Infection
Funder
National Health and Medical Research Council
Funding Amount
$605,096.00
Summary
Asthma exacerbations due to viral infections are a major health and economic burden to our society. Treatment of asthma exacerbations focuses on reducing the symptoms rather than the cause of the disease. Virus-induced asthma exacerbation are widely thought to be due to an abnormal influx of white blood cells into the lungs (inflammation) and an altered anti-viral responses. In this project we will explore novel strategies to inhibit inflammation and to promote the anti-viral response.