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.
Design And Delivery Of Peptide-based Anti-cancer Grb7 Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$603,126.00
Summary
The Grb7 protein is overproduced in many types of cancer cells and plays a role in cancer cell growth and spread. The current proposal builds upon the discovery of a peptide-based Grb7 inhibitor that has anti-cancer activity. This proposal is to prepare more potent inhibitor molecules that can efficiently reach the target cancer cells. Such molecules will be used for the study of Grb7 and for the development of a new Grb7-based anti-cancer drug therapy.
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.
Structure-based Design Of Novel Therapeutics For Multi-drug Resistant Neisseria Gonorrhoeae
Funder
National Health and Medical Research Council
Funding Amount
$669,148.00
Summary
Multiple drug resistance (MDR) in bacteria represents one of the most intractable problems facing modern medicine. The recent superbug, MDR-Neisseria gonorrhoeae (MDR-Ng), causes the sexually transmitted infection gonorrhoeae. A multi disciplinary team with expertise in structural biology, medicinal chemistry and bacteriology will establish a comprehensive knowledge base aimed at developing new antibiotics to treat MDR-Ng by targeting a bacterial protein virulence factor.
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.
Structural Biology And Therapeutic Targeting Of Proteins Involved In Infection And Immunity
Funder
National Health and Medical Research Council
Funding Amount
$753,300.00
Summary
Structural biology plays an essential role in uncovering how proteins function at the molecular level, and further facilitates strategies to develop therapeutics targeting the diseases these proteins are involved in. In the proposed work, I will focus on bacterial virulence factors, to develop new antibiotics and vaccination strategies, and proteins involved in innate immunity pathways, to develop therapeutics against a number of associated disorders including chronic inflammatory diseases.
Acetohydroxyacid Synthase: A New Drug Target For Human Fungal Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$536,914.00
Summary
The aim is to discover new compounds that have the ability to reduce the growth of invasive human fungal pathogens including Candida albicans, Cryptococcus neoformans and Aspergillus nidulans. These infectious agents are highly prevalent in hospital patients that are immuno-compromised. The compounds have a common feature in that they prevent the synthesis of valine, leucine and isoleucine which are key metabolites required for the survival of these fungi in the human host.
Structural Studies On The Immune Effector Perforin: Developing Mechanism-based Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$1,116,594.00
Summary
Perforin is an essential weapon deployed by the human immune cells in order to destroy virally infected or cancerous cells. Despite this key role, unwanted or excessive perforin function can result in disease and can severely impact on successful treatment of leukaemia through bone marrow transplantation. This application aims to understand the molecular details of perforin function, and to apply this knowledge to develop perforin inhibitors.
A common characteristic of cancer is the failure of cells to die when they normally would. One of the problems with many cancer therapies is that they rely on the integrity of signalling pathways to the normal ‘death machinery’ of the cell to do their job. By understanding how the molecular death machine operates we are fashioning new drugs that can target it directly, thus bypassing the very pathways that are so frequently disrupted in tumour cells.