To Biochemically Trick P-Glycoprotein (Pgp) To Target Resistance Via Lysosomal Pgp
Funder
National Health and Medical Research Council
Funding Amount
$603,848.00
Summary
We have discovered an innovative biochemical strategy whereby our novel compounds exploit and trick a part of the detoxification machinery, that is the transporter, P-glycoprotein, to specifically kill drug resistant cancer cells. Herein, we take advantage of this biochemical mechanism to design novel and safe drugs to selectively target resistant tumours.
Microparticles And Selective Trait Dominance In Multidrug Resistant Cancers
Funder
National Health and Medical Research Council
Funding Amount
$478,115.00
Summary
Multidrug resistance (MDR) is the cause of treatment failure in 90% of patients with metastatic cancer. We recently discovered a novel resistance mechanism in which microparticles provide a vehicle for intercellular transfer of MDR. We now report that MP play an even more significant role in conferring MDR, by the ñre-templatingî of cancer cell traits. This has considerable potential for translation into clinical outcomes with the identification of alternative drug targets and therapeutics for t ....Multidrug resistance (MDR) is the cause of treatment failure in 90% of patients with metastatic cancer. We recently discovered a novel resistance mechanism in which microparticles provide a vehicle for intercellular transfer of MDR. We now report that MP play an even more significant role in conferring MDR, by the ñre-templatingî of cancer cell traits. This has considerable potential for translation into clinical outcomes with the identification of alternative drug targets and therapeutics for the circumvention of MDR clinically.Read moreRead less
Understanding Multidrug Resistance In Cancer: Identification Of The Substrate And Inhibitor Binding Sites In P-glycoprotein
Funder
National Health and Medical Research Council
Funding Amount
$284,343.00
Summary
Cancers expressing the multidrug transporter P-glycoprotein (P-gp) are resistant to chemotherapy. The clinical impact of P-gp is so large that the National Cancer Institute (USA) “profiles” all anticancer drugs for transport by P-gp, primarily because the mechanism of drug binding and transport by P-gp is unknown. The aim of this proposal is to understand the molecular details of how drugs bind to and interact with P-gp, a major step in our understanding of P-gp mediated chemotherapy resistance.
A Mechanistic Approach To Therapy Development For Chronic Traumatic Encephalopathy Using Small And Large Animal Models Of Concussion
Funder
National Health and Medical Research Council
Funding Amount
$492,844.00
Summary
Repeated concussion in athletes has recently been associated with the development of a neurodegenerative disorder known as chronic traumatic encephalopathy (CTE). While the neuropathology seems to be well characterised, the mechanisms associated with CTE development are not. This proposal will demonstrate that mechanically induced release of the neurotransmitter substance P accounts for much of the neuropathology in CTE, and will develop a novel therapy that will prevent such development.
HIV Phenotypes Important For The Establishment Of Persistent Reservoirs In The Central Nervous System And Which Impact Neurotropism And Neuropathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$762,492.00
Summary
This grant will determine whether or not the CNS is a reservoir for HIV and identify the cellular targets of persistent infection and type of HIV-1 present.
Envelope Glycoprotein Determinants Of HIV-1 Subtype C Tropism And Pathogenicity
Funder
National Health and Medical Research Council
Funding Amount
$657,745.00
Summary
HIV-1 subtype C is the most common subtype of HIV-w worldwide, yet we know comparatively little about how it causes disease in humans. This study will elucidate how HIV-1 subtype C evolves in patients to become more pathogenic over time.
Novel HIV-1 Glycoprotein Vaccines With Enhanced Presentation Of Broad Neutralization Epitopes
Funder
National Health and Medical Research Council
Funding Amount
$743,682.00
Summary
A prophylactic vaccine represents the best strategy for blocking HIV-1 transmission but one is not yet available. Current antiviral vaccines rely on neutralizing antibodies (NAbs) that block infection, however, current HIV-1 vaccine formulations do not induce broadly reactive NAbs (bNAbs). We have discovered a novel HIV-1 glycoprotein vaccination candidate with enhanced presentation of bNAb epitopes. We propose to determine if this vaccine induces effective bNAbs in experimental animals.
Studies On The Activation And Immunogenicity Of The HIV-1 Glycoproteins, Gp120-gp41
Funder
National Health and Medical Research Council
Funding Amount
$606,438.00
Summary
More than 34 million people were living with HIV-1 in 2011 with ~7,000 new infections still occurring daily. A prophylactic vaccine for HIV-1 is needed to stop its transmission, however, this goal is yet to be achieved. Our proposed studies will inform the design of prophylactic HIV-1 vaccines that act by making antibodies that neutralize the virus.
Elucidating Unique Molecular Mechanisms Involved In HIV-1 Subtype C Pathogenicity
Funder
National Health and Medical Research Council
Funding Amount
$710,989.00
Summary
Most people infected with human immunodeficiency virus (HIV) have subtype C virus (C-HIV) and live in Southern Africa and Central Asia. These regions are where the HIV pandemic is at its worst. However, we know very little about C-HIV. We have evidence that C-HIV evolves differently compared to other HIV-1 subtypes, which impacts the way it leads to AIDS. This project aims to characterise these unique molecular mechanisms, which may lead to vaccines and drugs that are optimised for C-HIV.
Topical microbicides are urgently required to protect women from the sexual transmission of HIV. Lactic acid is produced by bacteria that are normally present in the healthy female vaginal tract and is more potent in the inactivation of HIV compared to low pH alone. This study seeks to determine how lactic acid inactivates HIV and to undertake laboratory studies to determine its suitability for development as a topical microbicide to prevent HIV transmission.