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
Containment Potential And Risk Of Spread Of Artemisinin Resistant Plasmodium Falciparum
Funder
National Health and Medical Research Council
Funding Amount
$381,762.00
Summary
Significant gains have been made in the past decade in reducing falciparum malaria morbidity and mortality using artemisinin-base combination therapy (ACT) and insecticidal nets. However the recent emergence of artemisinin resistance threatens these achievements. This project will develop and use a mathematical model of malaria transmission incorporating resistance to the drugs in ACTs to investigate the probability and rate of spread of resistance into new areas endemic for malaria.
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.
The Role Of Parasite Adhesins In Plasmodium Falciparum Invasion Of Human Erythrocytes
Funder
National Health and Medical Research Council
Funding Amount
$385,434.00
Summary
Invasion of red blood cells is essential for the survival of malaria parasite within the human host. Red blood cell invasion is mediated by recognition of parasite proteins to specific blood surface receptors. My research focuses on understanding these parasite protein-host receptor interactions with emphasis on translating these findings as novel approaches for the prevention and treatment of malaria.
T-follicular Helper Cell Subsets That Induce Protective Anti-Plasmodium Falciparum Antibodies
Funder
National Health and Medical Research Council
Funding Amount
$456,262.00
Summary
Malaria claims at least half a million lives each year, the majority of them in children under the age of 5 years. In order to development effective vaccines malaria it is critically important that we increase our understanding of the key mechanisms governing the induction of protective immune responses in naturally exposed populations. This project will examine the role of one important cell subset - T-follicular helper cells - in the development of immunity against malaria.
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.
Effector Export In P. Falciparum Infected Human Erythrocytes
Funder
National Health and Medical Research Council
Funding Amount
$1,066,920.00
Summary
We will investigate malaria, a parasitic disease that kills over 450,000 people a year. We will explore how the parasite identifies, invades and remodels the host cells in which it lives, scavenging nutrients and hiding from the immune system. We will characterize the proteins involved in these critical events, as they are potential targets for drugs. We will study how parasites cause disease and how the host responds to infection.
A Novel Approach To Identify The Specific Antibody Characteristics Important For Protection From Malaria In Pregnant Women
Funder
National Health and Medical Research Council
Funding Amount
$1,011,223.00
Summary
Antibody protects against malaria, but the specific characteristics of protective antibody are unknown. Pregnant women lack antibody to parasite protein called VAR2CSA, explaining their malaria susceptibility. Using samples from vaccine trials and clinical studies in pregnant women, and a ‘Systems Serology’ approach, we will determine which naturally-acquired or vaccine induced antibodies protect pregnant women from malaria, and how variation in VAR2CSA sequences affects this protection.
Breaking Malaria's Lethal Grip: Targeting The Assembly Of An Adhesive Complex On Infected Red Blood Cells
Funder
National Health and Medical Research Council
Funding Amount
$817,426.00
Summary
The malaria parasite, Plasmodium falciparum, infects the red blood cells of its human victims. It causes them to stick to blood vessel walls in the brain, causing severe cerebral complications and death. Adhesion is mediated by a Velcro-like protein that is presented at the red blood cell surface. This project will fully elucidate the pathway for trafficking of the adhesion protein to the red blood cell surface with a view to finding new ways of interfering with malaria disease.