Aurora Kinase: Molecular, Cellular And Functional Studies Deciphering Its Role In Stroke Injury
Funder
National Health and Medical Research Council
Funding Amount
$580,993.00
Summary
In stroke patients, oxygen deprivation indirectly induces massive nerve cell death by activating an enzyme called aurora kinase A (AURKA). We aim at unravelling (i) how AURKA is activated by oxygen deprivation, (ii) where the activated AURKA is localised in cells, and (iii) how the activated AURKA induces nerve cell death.The study will benefit development of therapeutic strategies to protect against brain damage in stroke since this is novel and different target for drug targeting.
Benefits And Safety Of IRon Supplementation With MAlaria Chemoprevention To Children In Malawi (IRMA) - A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$3,064,309.00
Summary
Anaemia and malaria frequently coexist in low income settings e.g. sub-Saharan Africa and Asia. Iron interventions aim to reduce anaemia but exacerbate malaria. We aim to test whether iron is made safe by coadministering malaria prevention, and whether these interventions improve child health outcomes especially cognitive development, while ensuring malaria resistance does not emerge.
In 2013 there were ~200 million clinical cases of malaria, causing ~600,000 deaths. All antimalarial drugs are now associated with malaria parasite resistance. Thus, new therapies are urgently needed, including new drugs to prevent this disease. We have made the exciting discovery that an existing antimalarial drug can kill malaria parasites in a unique, previously unknown, manner. Here, we will investigate how this occurs and develop new drug candidates for malaria prevention.
The Mezzanine T Cell Response: Intervening At The Coal Face
Funder
National Health and Medical Research Council
Funding Amount
$765,585.00
Summary
In an initial immune response, specialised cells in lymph nodes tell T cells to multiply; the stimulated T cells depart and enter target tissue (e.g. lung in the case of flu). We describe a new response whereby the target tissue itself can tell T cells to multiply further. This response in target tissues reveals a new way of altering immune responses. This is especially important as in many diseases, the primary lymph node response has already occurred, so cannot be therapeutically intervened.
A Longitudinal Neuroimaging Study Investigating Reorganisation Of Cerebellar-cerebral Networks In Friedreich Ataxia
Funder
National Health and Medical Research Council
Funding Amount
$816,908.00
Summary
Friedreich ataxia (FRDA) causes debilitating motor and cognitive deficits. We propose a longitudinal multi-modal magnetic resonance (MR) imaging study to measure different types of tissue in the brain in this disease. We seek to understand how the brain reorganises itself due to cell loss in the spinal cord, cerebellum and cerebral cortex. This study will establish sensitivity of a range of MR imaging measures as potential biomarkers for use in large multi-centre drug trials in this disease.
Targeting Adenosine Mediated Immunosuppression To Enhance CAR T Cell Activity
Funder
National Health and Medical Research Council
Funding Amount
$633,447.00
Summary
The use of white blood cells genetically engineered to eradicate cancer cells specifically has been a major breakthrough in cancer treatment. These cells (CAR T cells) are very effective in blood cancers, but do not currently work well in other cancers. This is due to the immune suppressing nature of the cancer environment. I propose to use strategies to overcome this by genetically reprogramming the CAR T cells to be resistant to suppression by the cancer and therefore be more effective.
Interplay Between Metabolic Reprogramming And Oncogenic Signalling In The Cellular Response To Chemotherapy
Funder
National Health and Medical Research Council
Funding Amount
$654,035.00
Summary
Chemotherapy resistance is a major barrier to the treatment of triple-negative breast cancer (TNBC). We seek to uncover an intimate link between cell metabolism and oncogenic signalling pathways in regulating the cellular response to chemotherapy. Our studies will identify a critical mechanism limiting the therapeutic efficacy of chemotherapy and investigate combination therapy strategies that could improve the treatment of TNBC.
A Simple Method To Improve Stem Cell Transplant Therapy
Funder
National Health and Medical Research Council
Funding Amount
$831,652.00
Summary
Despite the success of hematopoietic stem cell transplantation and years of promise, almost all other stem cell therapies are considered experimental and remain in preclinical or early-phase clinical testing. This study aims to improve the efficiency of stem cell transplantation by manipulating cellular metabolism prior to transplantation, if effective these results may offer hope to patients suffering from a broad range of disorders.
Evaluating Cancer Screening: Context, Evidence, Values And Ethics
Funder
National Health and Medical Research Council
Funding Amount
$572,460.00
Summary
The research and clinical communities are divided over whether certain forms of cancer screening do more harm than good. This project asks: What is the right thing to do about cancer screening now? Using robust qualitative methodologies, we will study real cases of cancer screening and analyse their ethical implications. Drawing on this data and analysis, we will produce tools to help policy-makers, consumers and professionals make good decisions about cancer screening in future.
A New Function For An Old Enzyme: Src Protein Kinase Directs Excitotoxic Neuronal Death In Stroke
Funder
National Health and Medical Research Council
Funding Amount
$513,975.00
Summary
In our previous investigation of how brain cells die in patients suffering from stroke, we found that stroke causes aberrant activation of an enzyme called Src in the affected brain cells. Furthermore, this aberrantly activated Src directs the brain cells to undergo cell death. Our proposal, which aims to decipher this neurotoxic mechanism of the aberrantly activated Src will benefit development of new therapeutic strategies to reduce brain damage in stroke patients.