Afinity Maturation And Development Of An Anti-inflammatory Monoclonal Antibody
Funder
National Health and Medical Research Council
Funding Amount
$387,489.00
Summary
Antibodies are a relatively new class of drugs that directly target molecular mechanisms of disease. Antibody therapies, such as the breast cancer drug Herceptin, have significantly increased our arsenal of effective therapeutics. In collaboration with G2 Therapies, we will use cutting-edge genetic engineering technology to produce fully human antibodies for the treatment of inflammatory diseases, such as rheumatoid arthritis.
Structural Studies Of The Jak And Abl Kinases: A Prerequisite For Drug Design
Funder
National Health and Medical Research Council
Funding Amount
$360,965.00
Summary
Protein tyrosine kinases (PTK) are a large, pivotal family of signalling molecules implicated in diseases such as cancer and immune related disorders. This fellowship aims to develop more potent kinase inhibitors of a number of PTKs using Cytopia’s drug discovery capability coupled with the X-ray crystallography expertise within Monash University. This innovative approach will permit a rational structure-based drug discovery platform to be established and will lead to the creation of a portfolio ....Protein tyrosine kinases (PTK) are a large, pivotal family of signalling molecules implicated in diseases such as cancer and immune related disorders. This fellowship aims to develop more potent kinase inhibitors of a number of PTKs using Cytopia’s drug discovery capability coupled with the X-ray crystallography expertise within Monash University. This innovative approach will permit a rational structure-based drug discovery platform to be established and will lead to the creation of a portfolio of phase I therapeutics, which will be of substantial benefit in the medical health area.Read moreRead less
Optimising The Therapeutic Efficacy Of Protein-based Drugs Against Lymph-resident Diseases
Funder
National Health and Medical Research Council
Funding Amount
$348,330.00
Summary
Effective treatments for lymphatic diseases (such as HIV and lymph-metastatic cancers) are limited by the lack of drug assess towards the lymphatic sites of disease progression. Improving the access of drugs into lymph therefore has the significant potential to improve the treatment of these illnesses. We will therefore explore a novel approach to improving the lymphatic uptake and retention of protein-based drugs using a useful and widely used biologically compatible polymer.
Bioengineering Of Cyclotides With Angiogenic Properties
Funder
National Health and Medical Research Council
Funding Amount
$488,273.00
Summary
Atherosclerosis, a gradual clogging of the arteries, is the single leading cause of death in Australia, Europe, the USA and Japan. Coronary heart disease (CHD; clogging of the coronary arteries), while secondary to atherosclerosis in most of the world, accounts for nearly 2 million deaths per year in Europe alone. In Australia CHD is the single leading cause of death. This project is aimed at developing lead molecules for the development of therapeutics capable of stimulating revascularization ( ....Atherosclerosis, a gradual clogging of the arteries, is the single leading cause of death in Australia, Europe, the USA and Japan. Coronary heart disease (CHD; clogging of the coronary arteries), while secondary to atherosclerosis in most of the world, accounts for nearly 2 million deaths per year in Europe alone. In Australia CHD is the single leading cause of death. This project is aimed at developing lead molecules for the development of therapeutics capable of stimulating revascularization (that is, opening up blocked vessels to improve blood flow) of tissues with slow or retarded circulation. Such therapeutics would improve the treatment of atherosclerosis and CHD. Peptides, small proteins, are generally not stable enough to be used as drugs. In this project we plan to engineer protein molecules based on an unusually stable family of proteins, known as the cyclotides. We will chemically synthesise analogues of cyclotides that have been altered to incorporate the activities of less stable small peptides that are able to induce therapeutic angiogenesis. Given the prevalence of CHD, the development of effective therapeutics could have a profound impact on the economic cost of the disease, which in the USA amounts to US$133.2 billion per year. This project involves collaboration between researchers from the Institute for Molecular Bioscience, who have expertise in drug design and protein chemistry, and researchers from the Centre for Research in Vascular Biology, who have expertise in vascular biology and vessel engineering. Both of these institutes are part of the University of Queensland.Read moreRead less
Development Of A Novel Orally Active Peptide For The Treatment Of Pain
Funder
National Health and Medical Research Council
Funding Amount
$402,145.00
Summary
Chronic pain from damage to the nervous system is difficult to treat. A new type of drug has recently been developed from sea snail venom to treat chronic pain but is given by injection, which limits its use. Our research has developed a stable molecule that has analgesic activity when ingested. This proposal focuses on further testing to fully establish this molecule's therapeutic potential. This information can then attract a commercial partner to bring the new drug into general use.
Professor Ashley Bush has extensively researched the contribution of metal biochemistry to Alzheimer�s and Parkinson�s diseases. In the current proposal he will lead the clinical testing of a new drug that combats the abnormal accumulation of metals in Alzheimer�s brain pathology, he will search for abnormal metal-interactions with blood proteins as a potential predictive test, and he will study the roles of various brain proteins in regulating metal levels to maintain healthy function.
There is an ongoing need for the development of new anticancer drugs, particularly those directed against solid tumours. In the past plants have been an extremely valuable source of anticancer agents, including the world s best selling anticancer drug, Taxol, isolated from the Pacific Yew tree. However, such molecules are typically complex and often very expensive to manufacture or extract from natural sources. So far very little attention has been paid to protein-based molecules from plants as ....There is an ongoing need for the development of new anticancer drugs, particularly those directed against solid tumours. In the past plants have been an extremely valuable source of anticancer agents, including the world s best selling anticancer drug, Taxol, isolated from the Pacific Yew tree. However, such molecules are typically complex and often very expensive to manufacture or extract from natural sources. So far very little attention has been paid to protein-based molecules from plants as potential anticancer agents because pharmaceutical companies have focused on organic molecules. In principle protein-based molecules could be produced much more cheaply and thus made available more widely to patients than existing drugs. All that is required are the lead molecules, or proteins that display sufficient anticancer activity to be used as the basis for further optimization. We have discovered a family of plant proteins called the cyclotides that have recently been shown to have considerable promise as anticancer agents. In the current project we will use synthetic chemistry to modify selected amino acids on the surface of this new family of proteins to determine which parts of the molecules are responsible for their activity. We will use this information to design improved analogues. The project is a collaboration between researchers at the Institute for Molecular Bioscience, University of Queensland, who have expertise in the required peptide chemistry and researchers and clinicians at Uppsala University, Sweden who have a range of assays and clinical expertise to test the new molecules. Both groups have been centrally involved in the discovery of the cyclotide family of plant proteins and are committed to developing them as exciting new anticancer agents.Read moreRead less
Chronic pain affects 1 in 5 Australians and neuropathic pain is among the most severe forms of chronic pain. Several peptides derived from cone snail venoms have attracted recent attention as potential therapeutic agents for the treatment of neuropathic pain. One of these, conotoxin MVIIA, has recently been approved in the US and Europe and others, including CVID and ACVI, are in various stages of clinical investigation. These small disulfide rich peptides share the attractive features of peptid ....Chronic pain affects 1 in 5 Australians and neuropathic pain is among the most severe forms of chronic pain. Several peptides derived from cone snail venoms have attracted recent attention as potential therapeutic agents for the treatment of neuropathic pain. One of these, conotoxin MVIIA, has recently been approved in the US and Europe and others, including CVID and ACVI, are in various stages of clinical investigation. These small disulfide rich peptides share the attractive features of peptides in general of having exquisite selectivity for particular receptors, but also share the general disadvantages of peptides of short biological half-lives and poor bioavailablility. Stabilisation of these conotoxins has the potential to substantially increase their therapeutic potential. In preliminary studies we have shown that by introducing a circular petide backbone into a conotoxin using a linker sequence we can increase its stability and resistance to enzymatic degradation. We therefore propose that it will be possible to cyclise a wide range of conotoxin molecules and thereby improve their drug like properties. In this project we will use our cyclisation approach to develop new potential treatments for pain from two classes of conotoxins. One of the lead molecules shows oral bioavailability in an animal pain model and potentially represents a major breakthrough in the field of peptide drug delivery.Read moreRead less