Identifying Novel Antimalarial Targets Using ENU Mutagenesis In The Mouse
Funder
National Health and Medical Research Council
Funding Amount
$760,170.00
Summary
Malaria is estimated to cause 1.2 million deaths per year. The malarial parasite has developed resistance to most drugs and new drugs are needed. We aim to mimic the protective red blood cell diseases common in human populations in malarial endemic areas by identifying host targets that are important in parasite growth.
Molecular Regulation Of Pluripotency In The Mammalian Germline
Funder
National Health and Medical Research Council
Funding Amount
$611,935.00
Summary
Germ cells generate sperm in males or oocytes in females. In males, germ cell numbers are tightly controlled in the embryo, with too few germ cells causing infertility, and unrestrained germ cell numbers leading to testicular cancer. We have discovered a molecular mechanism that regulates germ cells in the embryo, and propose to study in mice how this regulation is accomplished and the consequences of defective regulation, in order to learn more about how infertility and testis cancer arise.
6% of Australian men are infertile. Of these cases 50% are thought to be genetic in origin. Within this project we will replicate high-confidence genetic variants associated with human male infertility in the mouse. Doing so will allow the assignment of definitive genotype-phenotype correlations and the formulation of high confidence advice for clinicians and patients. It will also provide a means to define the mechanism of action and the tools for future pro-fertility treatments.
Deciphering Mechanisms Of Disease Evolution In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$845,093.00
Summary
In many patients, cancers are ever-changing, even after they have formed. This explains why many cancers can spread beyond the point of cure by surgery and why they can become resistant to treatments. This project will use patient melanomas and laboratory modelling to understand how melanomas change as they grow and spread. The results will be used to identify the nature of evolutionary changes in cancer in order to predict and even exploit them in treatment.
Integrative Bioinformatic And Experimental Approaches To Define Novel Roles For Genes That Typically Regulate Axon Guidance In Pancreatic Cancer Initiation
Funder
National Health and Medical Research Council
Funding Amount
$587,955.00
Summary
Early detection and intervention would have a dramatic effect on improving the outcomes for pancreatic cancer. This however relies on understanding how the cancer is initiated. New analysis of more than 100 tumours identified aberrations in genes that typically regulate how the nervous system is positioned during development. We want to use novel bioinformatic approaches and a unique experimental method with cells in culture to rapidly and accurately find out which of these genes drives a normal ....Early detection and intervention would have a dramatic effect on improving the outcomes for pancreatic cancer. This however relies on understanding how the cancer is initiated. New analysis of more than 100 tumours identified aberrations in genes that typically regulate how the nervous system is positioned during development. We want to use novel bioinformatic approaches and a unique experimental method with cells in culture to rapidly and accurately find out which of these genes drives a normal pancreatic cell to become a tumour cell.Read moreRead less
Obesity is a major global public health concern and there is a desperate need to identify new targets to treat obesity. By targeting the lesser investigated CART pathway and identifying the elusive CART receptor this could make a significant inroad to the understanding of the causes of appetite control and the development of obesity.
Role Of ZEB/NuRD Interactions In Haematopoiesis And Lymphoid Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$810,497.00
Summary
Cancers of the blood arise from (epi)genetic changes that enable blood cells to bypass normal survival and growth checkpoints, leading to accumulation of additional mutations that drive full-scale transformation. This grant aims to understand the role of specific transcription factors (that control disease causing genes to be expressed) and how we can use a novel class of epigenetic drugs together with inhibition of these factors to selectively get rid of cancer causing blood cells in the body.
The Role Of Necroptosis In Development, The Immune System And Autoimmune Pathology
Funder
National Health and Medical Research Council
Funding Amount
$454,105.00
Summary
Programmed cell death plays critical roles in development and cell-turnover in the adult. Defects in this process can cause cancer or autoimmune diseases. We will use genetic and biochemical approaches to define the individual roles of necroptosis, a newly described cell death process, and those overlapping with apoptosis in normal development and cell-turnover as well as in cancer and autoimmune diseases. The objective of this work is to identify potential targets for therapeutic intervention i ....Programmed cell death plays critical roles in development and cell-turnover in the adult. Defects in this process can cause cancer or autoimmune diseases. We will use genetic and biochemical approaches to define the individual roles of necroptosis, a newly described cell death process, and those overlapping with apoptosis in normal development and cell-turnover as well as in cancer and autoimmune diseases. The objective of this work is to identify potential targets for therapeutic intervention in cancer or immunopathology.Read moreRead less
A Novel Role For Proteolysis In Promoting Inner Ear Cell Injury And Hearing Loss
Funder
National Health and Medical Research Council
Funding Amount
$972,818.00
Summary
Nearly 40% of hearing loss is attributable to traumatic noise exposure. This project will test a new idea that cells in the inner ear are damaged and die via noise-induced proteolysis, and investigate whether a similar mechanism operates during age-related hearing loss. It will open new avenues for therapies to preserve hearing where trauma is unavoidable, or has occurred through accident or incident.
Targeting Neuroserpin-plasmin Interactions To Protect The Retina In Glaucoma
Funder
National Health and Medical Research Council
Funding Amount
$648,965.00
Summary
Glaucoma causes blindness and despite our best treatment many patients continue to progress. A new approach is needed to protect the cells that die in the retina. We have established that a common protease – plasmin – is involved in the process, and a protein that normally regulates it – neuroserpin – is downregulated in the disease. We aim to modify neuroserpin using an ocular gene therapy approach and show it could be used as a novel therapy in glaucoma.