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.
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.
Ketol-acid Reductoisomerase: An Important Antituberculosis Drug Target
Funder
National Health and Medical Research Council
Funding Amount
$690,113.00
Summary
Due to the increasing prevalence of drug resistance, new antituberculosis medications are urgently needed. Here, we will use rational structure-based approaches to design new inhibitors of ketolacid reductoisomerase (KARI), an enzyme whose activity is essential to the survival of this pathogen that resides in the lungs of humans. These inhibitors will be converted into prodrug formulations for optimal activity in cell-based assays and in mice infected with this pathogen.
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.
Professor Michael Parker from St Vincent’s Institute in Melbourne is one of Australia’s leading structural biologists. He will use his Fellowship to help establish a Cancer Structural Biology Centre to provide early stage drug discovery tools which will aid many of Australia’s leading cancer researchers to translate their basic discoveries into drugs. This work will utilise key major infrastructure investments including the Australian Synchrotron.
Investigating The Substrate Specificity Of The Master Kinase LKB1 And The Pharmacological Targeting Of Its Substrate NUAK2 To Treat Cancers
Funder
National Health and Medical Research Council
Funding Amount
$384,768.00
Summary
Kinases are key regulators of cell signaling and emerging drug targets. LKB1 kinase specifically activates a set of substrates to modulate cellular processes, and its substrate NUAK2 is a novel target for cancer. I will elucidate the structural basis of how LKB1 recognizes its substrates and develop inhibitors targeting LKB1-NUAK2 interaction for cancer treatment. My project will provide key insights into kinase-dependent signaling and establish a new framework for therapeutics development.
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.
Structural Studies Of The Molecular Machinery Regulating Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$638,517.00
Summary
Our bodies use a process called Programmed Cell Death to remove unwanted or dangerous cells. This work aims to understand the machinery that regulates this process at the molecular level. These insights will inform the development of drugs aimed at either initiating cell death when required, for example in cancer, or at inhibiting it when excessive cell death causes disease.
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.