Development Of Next Generation Drugs For Chronic Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$632,726.00
Summary
Chronic myeloid leukaemia (CML) is one of the four most common types of leukaemia. With current therapies, 15–20% of patients newly diagnosed for CML will die in the next five years, and it is therefore vitally important to discover new treatments. The aim of this project is to develop a new generation of drugs to treat CML based on new approaches (i.e., different type of molecules and different binding site) that can combat the resistance acquired to the current treatments.
We aim to develop a new class of cholesterol-lowering drugs by blocking the interaction between a protein in the blood called PCSK9 and its receptor, which is implicated in cholesterol absorption. We will do this by designing small stable peptides (mini proteins) that mimic part of the receptor and have the potential to interfere with the normal PCSK9 binding process. These drugs should be less expensive and potentially less immunogenic than competing therapies based on antibodies.
Development Of Peptide-based Scaffolds For Intracellular Cancer Targets
Funder
National Health and Medical Research Council
Funding Amount
$1,479,836.00
Summary
The overall aim of this project is to develop peptide-based drugs that are able to cross cell membranes and inhibit specific targets inside cells leading to more effective, safer and cost effective drugs for cancer. One potential outcome of the project will be new drug leads to treat melanoma and leukemia that are likely to be less toxic, more potent and less likely to develop resistance than current treatments.
Selective Targeting Of Microbes By Peptides Of The Innate Immune System.
Funder
National Health and Medical Research Council
Funding Amount
$626,644.00
Summary
Cytolytic antimicrobial peptides (AMPs) are key components of the innate immune system of many organisms including man. They act by disrupting the outer membranes of bacteria, fungi and enveloped viruses. These simple peptides are highly specific and increasingly seen as a new source of antibiotic agents capable of combating the rising resistance to current drugs. Our aim is to determine the mechanism by which cytolytic AMPs act and to understand the factors that give rise to membrane and cell s ....Cytolytic antimicrobial peptides (AMPs) are key components of the innate immune system of many organisms including man. They act by disrupting the outer membranes of bacteria, fungi and enveloped viruses. These simple peptides are highly specific and increasingly seen as a new source of antibiotic agents capable of combating the rising resistance to current drugs. Our aim is to determine the mechanism by which cytolytic AMPs act and to understand the factors that give rise to membrane and cell specificity.Read moreRead less
A new source of bivalent molecules from nature. This project aims to describe a new class of naturally occurring multivalent molecules termed secreted cysteine-rich repeat proteins (SCREPs). Multivalency is a key feature of molecular interaction in biology, underlying the high specificity and potency found in many proteins. Focusing on bivalent peptides, the project will generate a database of bioactive SCREPs with similarity to known bioactive peptides, and develop new recombinant methods for t ....A new source of bivalent molecules from nature. This project aims to describe a new class of naturally occurring multivalent molecules termed secreted cysteine-rich repeat proteins (SCREPs). Multivalency is a key feature of molecular interaction in biology, underlying the high specificity and potency found in many proteins. Focusing on bivalent peptides, the project will generate a database of bioactive SCREPs with similarity to known bioactive peptides, and develop new recombinant methods for their production. The project will use advanced nuclear magnetic resonance spectroscopy to characterise members of this new class, providing new insights into the design of bivalent and multivalent peptides and establishing a new source of molecules with applications in the rapidly growing biotechnology sector.Read moreRead less
Molecular Interactions with an antibiotic target in DNA replication. This project aims to develop and use new technologies to address mechanistic aspects of anti-bacterial compounds in development, and of the development of resistance to them. The project will focus on the sliding clamp subunit of the bacterial replicative polymerase by studying its association with many other proteins in vitro and in vivo, using novel techniques in solid-state NMR, single-molecule fluorescence and molecular mic ....Molecular Interactions with an antibiotic target in DNA replication. This project aims to develop and use new technologies to address mechanistic aspects of anti-bacterial compounds in development, and of the development of resistance to them. The project will focus on the sliding clamp subunit of the bacterial replicative polymerase by studying its association with many other proteins in vitro and in vivo, using novel techniques in solid-state NMR, single-molecule fluorescence and molecular microbiology. The outcomes are expected to be an increased understanding of bacterial DNA replication and mechanisms of antibiotic action and resistance. This project expects to generate new knowledge to assist in combatting antibiotic resistance in Gram-negative bacterial pathogens.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120102857
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Innovative chemical tools for the isolation, biochemical and structural analysis of biological macromolecular assemblies. This project will develop a new approach for determining the three dimensional structures of protein complexes. This project will demonstrate this approach by determining the structure of a protein complex involved in gene regulation and disease.
Australian Laureate Fellowships - Grant ID: FL150100146
Funder
Australian Research Council
Funding Amount
$2,977,310.00
Summary
Taking Australia from the farm to the pharm. Taking Australian from the farm to the pharm: This fellowship project aims to design novel drugs based on cyclic peptides that will be expressed in the seeds of plants to produce bio-pills — saving money for patients and the health care system. Plants produce unique cyclic peptides (mini-proteins) to protect themselves from pests and pathogens. This project aims to chemically redesign these peptides to produce stable protein-based pharmaceuticals that ....Taking Australia from the farm to the pharm. Taking Australian from the farm to the pharm: This fellowship project aims to design novel drugs based on cyclic peptides that will be expressed in the seeds of plants to produce bio-pills — saving money for patients and the health care system. Plants produce unique cyclic peptides (mini-proteins) to protect themselves from pests and pathogens. This project aims to chemically redesign these peptides to produce stable protein-based pharmaceuticals that can be eaten. It is hoped that these designer pharmaceuticals will be inexpensive, effective, easy to ingest and without the side effects of traditional drugs. The outcomes of this project are anticipated to be high-value drugs and agri-chemicals which will open up new high-value crops for Australian farmers and a new Australian ‘pharming’ industry.Read moreRead less
Understanding peptide bond formation in non-ribosomal peptide biosynthesis. This project aims to uncover the origins of selectivity exhibited by the biosynthetic machinery that produces non-ribosomal peptides through advancing our understanding of how the central peptide synthesis domain functions. This project intends to generate new knowledge about peptide biosynthesis using a highly interdisciplinary approach and essential tools that have been developed. The anticipated outcomes of this proje ....Understanding peptide bond formation in non-ribosomal peptide biosynthesis. This project aims to uncover the origins of selectivity exhibited by the biosynthetic machinery that produces non-ribosomal peptides through advancing our understanding of how the central peptide synthesis domain functions. This project intends to generate new knowledge about peptide biosynthesis using a highly interdisciplinary approach and essential tools that have been developed. The anticipated outcomes of this project will be an enhanced understanding of the structural basis for substrate selection exhibited during peptide synthesis, revealing the specificity code of these key domains. This knowledge is vital for future efforts to reengineer such biosynthetic peptide assembly lines to produce new bioactive peptides.Read moreRead less
The chemistry and biology of circular proteins. This project aims to develop plant-derived ultra-stable cyclic peptides for pharmaceutical and agricultural applications. The project will use innovative new methodologies for discovery, chemical synthesis and engineering of these molecules. It is expected that the project will contribute to high value biotechnology and agricultural industries in Australia. The proposed outcomes will include fundamental new knowledge on the biosynthesis of circular ....The chemistry and biology of circular proteins. This project aims to develop plant-derived ultra-stable cyclic peptides for pharmaceutical and agricultural applications. The project will use innovative new methodologies for discovery, chemical synthesis and engineering of these molecules. It is expected that the project will contribute to high value biotechnology and agricultural industries in Australia. The proposed outcomes will include fundamental new knowledge on the biosynthesis of circular proteins in plants, new approaches for their discovery and technologies for applying them as drug leads and agricultural products.Read moreRead less