Mechanisms Of Action Of The Trefoil Peptides In Promoting Healing In Models Of Inflammatory Bowel Disease
Funder
National Health and Medical Research Council
Funding Amount
$365,270.00
Summary
Preliminary experiments from our laboratory have shown that members of a family of small proteins called trefoil peptides, found naturally in the stomach, intestine and colon, are able to shorten the healing time of ulcers and reduce inflammation, in an animal model of inflammatory bowel disease. Crohn's disease and ulcerative colitis together make up the human inflammatory bowel diseases, or IBD for short. They afflict many members of the community, are debilitating, expensive to treat, and cur ....Preliminary experiments from our laboratory have shown that members of a family of small proteins called trefoil peptides, found naturally in the stomach, intestine and colon, are able to shorten the healing time of ulcers and reduce inflammation, in an animal model of inflammatory bowel disease. Crohn's disease and ulcerative colitis together make up the human inflammatory bowel diseases, or IBD for short. They afflict many members of the community, are debilitating, expensive to treat, and current treatments like corticosteroids and suppressors of the immune system have unpleasant and health-threatening side effects. There are therefore good reasons for the development of new forms of therapy which will be better tolerated and which are specific in their actions. We believe that the trefoil peptides may be good candidates on which new treatments for inflammatory disease might be based. The studies outlined in this proposal will test the best route of administration, and how often to give trefoil peptides in order to relieve the symptoms of experimental IBD. In addition the effectiveness of the trefoils will be compared to other agents currently used in IBD treatment, or which are known to relieve inflammation or speed the healing of the ulcerated colon. We will also carry out experiments designed to work out the mechanisms by which the trefoils' healing effects are mediated, and finally we will characterise a new member of the trefoil peptide family which we have recently discovered.Read moreRead less
Elucidation Of Mechanisms By Which Fibre Promotes Or Protects From Colorectal Tumorigenesis
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
In a carefully controlled animal model of colon cancer development, dietary fibre can increase or decrease the likelihood of colon cancer development. It depends upon the type of fibre being fed to the animal. The mechanisms by which fibres can increase or decrease the likelihood of colon cancer developing are, however, poorly understood. In this proposal, we will attempt to elucidate at least some of the mechanisms. We plan to define whether animals consuming fibres that increase cancer develop ....In a carefully controlled animal model of colon cancer development, dietary fibre can increase or decrease the likelihood of colon cancer development. It depends upon the type of fibre being fed to the animal. The mechanisms by which fibres can increase or decrease the likelihood of colon cancer developing are, however, poorly understood. In this proposal, we will attempt to elucidate at least some of the mechanisms. We plan to define whether animals consuming fibres that increase cancer development have factors in their faeces that affect the health of the cells that line the colon (the ones that form the cancers). This will be examined in both the test tube and in healthy rats. Whether fibres influence the access of these factors to the lining cells by sequestering or hiding the factors in the jelly-like consistency some fibres produce in the colon will also be examined. The results will help identify conditions in the faeces that alter the susceptibility of colons to developing cancer. By identifying these conditions, we can then apply our knowledge to human subjects, so that we might be able to identify those at a higher or lower risk of developing colon cancer and we can advise and (subsequently prove) ways of modifying diet to reduce the risk of colon cancer.Read moreRead less
Immune Regulation, Effector Function And Human Therapy
Funder
National Health and Medical Research Council
Funding Amount
$11,474,346.00
Summary
The immune system plays an important role in protecting the host from viral and bacterial infections, and inhibits cancer onset and progression. Immune processes proceed through specialised cells in conjunction with soluble factors such as inteferons and interleukins. These soluble factors can regulate the activities of immune cells, and inhibit the growth and survival of aberrant (virus infected, cancer) cells. Unfortunately, the immune system can sometimes lose specificity and attack the host, ....The immune system plays an important role in protecting the host from viral and bacterial infections, and inhibits cancer onset and progression. Immune processes proceed through specialised cells in conjunction with soluble factors such as inteferons and interleukins. These soluble factors can regulate the activities of immune cells, and inhibit the growth and survival of aberrant (virus infected, cancer) cells. Unfortunately, the immune system can sometimes lose specificity and attack the host, resulting in autoimmune diseases such as diabetes. This research team has played a vital role in characterising the specific activities of immune cells and the associated factors. Importantly, they are deciphering the intricate communication networks of these immune components and dissecting their modes of action. By understanding these complex processes, the team aims to harness the unique therapeutic properties of our own immune system and translate their findings into the clinic. The team is developing new immune-based therapies for use, either alone or in combination with existing chemotherapies to fight debilitating human diseases such as cancer and autoimmune disease.Read moreRead less
Discovering How A Novel Anti-malarial Drug Series Rapidly Kills Parasites
Funder
National Health and Medical Research Council
Funding Amount
$672,971.00
Summary
We have developed a new set of highly potent anti-malarial drugs but we do not know how they work. Identifying how these compounds work is important for improving their effectiveness and safety. We will discover how these drugs kill parasites by using a number of cutting edge methods that could also be useful for discovering how other drugs work. Data generated will progress these compounds along the drug development pipeline which urgently needs a constant supply of new antimalarials.
Development Of Peripheral Sensory Pathways In Humans
Funder
National Health and Medical Research Council
Funding Amount
$477,504.00
Summary
To receive the appropriate information about the state of our muscles, joints, organs, and skin we need a properly 'connected' sensory system. Recent evidence suggests traumatic events during early development can alter sensory connections within the spinal cord. This can lead to debilitating movement disorders, digestive diseases, and increased pain. In this study we will examine how peripheral sensory fibres connect with the appropriate nerve cells in the human spinal cord during development.
Investigation Into The Alternative Splicing Of Steroid Hormone Regulated Genes In Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$292,216.00
Summary
Steroid hormones have imortant roles in breast tissue growth and differentiation. We have identified several proteins called PRMT6 and CAPER's , that are involved in steroid hormone signaling and control the alternative splicing of RNA, the process in which several different proteins can be produced from a single gene. Our aim is to study these proteins in an effort to understand how they influence alternative splicing and to identify genes they control in relation to breast cancer.
Targeting Cancer-initiating Cells With DNA Methyltransferase Inhibitors: Single-cell Analysis To Decipher Molecular Mechanisms And Improve Efficacy.
Funder
National Health and Medical Research Council
Funding Amount
$175,000.00
Summary
Certain cancer cells, termed cancer-initiating cells (CICs), have special properties allowing them to drive cancer growth and disease progression. These cells are particularly sensitive to low-dose treatment with drugs called DNA methyltransferase inhibitors. Using cutting-edge "single-cell" technologies this project will determine how these drugs target CICs and identify new ways to increase treatment efficacy. This work will identify new clinical opportunities for prevention of cancer relapse.
Retargeting The Antibiotic Azithromycin As An Antimalarial With Dual Modality.
Funder
National Health and Medical Research Council
Funding Amount
$773,613.00
Summary
Malaria parasites resistant to first-line treatments continue to spread in South East Asia. New drugs need to be developed urgently to ensure alternative treatment strategies are available. We will retarget the safe and widely used antibiotic azithromycin as an antimalarial with dual modalities against parasite invasion and growth inside the host red blood cell. This strategy has significant potential to increase drug efficacy while reducing the chances for the development of resistance.
Understanding And Targeting Coenzyme A Biosynthesis And Utilisation In Plasmodium Falciparum.
Funder
National Health and Medical Research Council
Funding Amount
$556,114.00
Summary
This grant describes a series of studies designed to understand how the human malaria parasite P. falciparum metabolises vitamin B5, an essential molecule for the parasite. We will also carry out experiments to determine how a new series of vitamin B5 analogues we have developed kill the parasite and aim to start developing these compounds into new and much needed antimalarial medications.
Combined Therapy To Ameliorate Ventilatory Instability In Patients With Heart Failure And Sleep Apnea
Funder
National Health and Medical Research Council
Funding Amount
$386,648.00
Summary
Sleep apnea is highly prevalent, particularly in patients with heart failure, and treatment remains limited to applying pressure via a face mask which can be intolerable. Although instability in breathing control is a major cause of apnea in many patients, treatments targeting instability with sufficient efficacy are unavailable. This project will combine two treatments, acetazolamide and oxygen, to powerfully reduce instability and provide relief from sleep apnea in a subgroup of patients.