Improving Muscular Dystrophy By Targeting The ADAMTS5 Metalloproteinase
Funder
National Health and Medical Research Council
Funding Amount
$658,571.00
Summary
Muscular dystrophy is a devastating childhood disorder. There is no cure and no effective therapy to stop the disease progressing to early death. Our pilot data show that muscular dystrophy in a mouse model is dramatically improved when the Adamts5 gene is inactivated. ADAMTS5 is an enzyme that remodels the extracellular matrix around cells. This suggests that inhibiting ADAMTS5 may be a new way to treat muscular dystrophy. We will test this idea in mice with muscular dystrophy
Functional Analysis Of The Toxoplasma Myosin Driving Tissue Dissemination And Host Cell Invasion
Funder
National Health and Medical Research Council
Funding Amount
$763,241.00
Summary
The single-celled parasite Toxoplasma gondii is the cause of Toxoplasmosis and is an important basis of eye disease, congenital birth defects and illness in immunocompromised individuals. To perpetuate infection T. gondii moves through tissue and invades host cells using a molecular motor, termed the 'glideosome'. We will reveal how the glideosome produces the force required for movement and characterise its critical features. Our work will provide a foundation in which to model novel drugs that ....The single-celled parasite Toxoplasma gondii is the cause of Toxoplasmosis and is an important basis of eye disease, congenital birth defects and illness in immunocompromised individuals. To perpetuate infection T. gondii moves through tissue and invades host cells using a molecular motor, termed the 'glideosome'. We will reveal how the glideosome produces the force required for movement and characterise its critical features. Our work will provide a foundation in which to model novel drugs that could be designed to treat Toxoplasmosis.Read moreRead less
Genetic Programs Orchestrated By AP-1 Transcription Factors In Colorectal Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$599,941.00
Summary
Colorectal cancer (CRC) is the third most common cancer worldwide. About half of all patients diagnosed with the disease die as a result of its spread in the body. This project will investigate the role that a specific DNA-binding protein plays in orchestrating gene expression programs required for CRCs to spread. The research will provide new insights into underlying mechanisms of CRC progression as well as identify new therapeutic targets for aggressive forms of the disease.
Characterisation Of Two Novel Markers Of Osteosarcoma Metastasis As Potential Therapeutic Targets
Funder
National Health and Medical Research Council
Funding Amount
$624,500.00
Summary
Osteosarcoma (OS) is the most common bone tumour in children and adolescents. In spite of aggressive chemotherapy, OS tumours that metastasise to the lungs result in dismal long-term survivals of only 10-20%. For these patients, new treatment options are desperately needed. In this proposal we show compelling data identifying two new markers of OS metastasis. This research aims to validate the suitability of these novel markers as therapeutic targets to prevent OS metastasis.
Mechanistic Basis Of AP-1-regulated Gene Expression During Colorectal Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$597,802.00
Summary
The spread of colorectal cancers in the body poses a major clinical problem for which current treatment options are inadequate. This project aims to unravel how a specific DNA-binding protein regulates the expression of genes involved in the spread of these cancers. The research is expected to provide a better mechanistic understanding of how disease progression occurs and to identify novel strategies to treat aggressive tumours.
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.
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.
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.