Epilepsy is a devastating disease with many patients poorly treated. We have identified a novel ion channel target in the brain that reduces seizure susceptibility. The aim of this proposal is to fully explore this target in a number of epilepsy mouse models using both pharmacology and molecular techniques.
Identifying Brain Pathways Responsible For Stress Induced Obesity
Funder
National Health and Medical Research Council
Funding Amount
$895,663.00
Summary
Obesity-associated diseases are leading causes of death and are expected to increase as the obesity epidemic worsens. New evidence also shows that stress, an ever-increasing factor of life, can when combined with high caloric food lead and accelerate the development of obesity. The results from this study will help to identify new agents that may help reduce body weight and fat mass particular under conditions of increased stress.
Molecular Characterization Of V-ATPase V0 Domain Subunits E1 And E2 In Osteoclast
Funder
National Health and Medical Research Council
Funding Amount
$558,909.00
Summary
Osteoporotic fractures in the elderly are often linked to increased mortality rates. Excess bone resorption is a major contributor to the onset of the disease. The proposed project focuses on the investigation of the molecular mechanisms of acid secretion that is required for the bone degradation in body. The project will examine the role of the proton pump in bone resorption and seek potential targets for the treatment of osteoporosis.
Epigenetic Regulation Of L1 Retrotransposition In Mouse Models Of Abnormal Human Neurobiology
Funder
National Health and Medical Research Council
Funding Amount
$417,812.00
Summary
Retrotransposons are mobile genes that copy-and-paste themselves to spread in DNA. Until very recently, they were thought to only be active in sperm and egg. In our recent work, we demonstrated that they also move in the brain. In the current study, we will use cutting-edge technologies to determine how retrotransposons change the genetic makeup of neurons in neurodevelopmentally impaired mice to predict whether these mutations would also be present in human brain disorders.
Deciphering The Overlapping Roles Of SSB1 And SSB2 In The Regulation Of Haematopoiesis And Intestinal Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$996,631.00
Summary
Our work centres on elucidating the role of two newly identified and related single-stranded DNA binding protein (Ssb1 and Ssb2) in development of blood and gut system. When both genes are deleted mice die with 8 days of knockdown due to bone marrow failure and intestinal atrophy. Our double knockout model parallels the consequences of radiation damage on blood and gut system. Toxicity to these systems is a significant hindrance in delivering anti-tumor therapy.
Problems in learning, memory and other complex mental processes are common to many brain disorders. This project will study the impact of mutations on a family of genes reported in autism and schizophrenia, on complex cognitive behaviours using novel behavioural technologies. This will not only shed fundamental insights into the specific mental processes regulated by these genes and their role in disease, but importantly provide novel targets for the development of therapies.
Novel Therapeutic Approaches To Ovarian Clear Cell Cancer
Funder
National Health and Medical Research Council
Funding Amount
$500,920.00
Summary
Our study aims to develop novel therapies for clear cell ovarian cancer, a disease that is generally resistant to conventional therapies. We have found unexpected parallels between kidney cancer and ovarian clear cell cancer, and this has been used to better treat patients. This study investigates the underlying molecular changes the control ovarian clear cell cancer growth.
Vitamin D Synthesis Within Osteoblasts Increases Bone Mineral By Regulating Remodelling: Is This The Link Between Vitamin D Status And Fractures?
Funder
National Health and Medical Research Council
Funding Amount
$627,082.00
Summary
This project will contribute to understanding mechanism of vitamin D action within bone to modulate bone resorption and offers the exciting prospect of identifying the mechanism by which an adequate vitamin D status can reduce the risk of osteoporotic hip fractures. Thus, this project has great potential to improve community health by being able to recommend vitamin D supplementation made on the basis of maintaining normal bone cell function with psarticular reference to modulating bone resorpti ....This project will contribute to understanding mechanism of vitamin D action within bone to modulate bone resorption and offers the exciting prospect of identifying the mechanism by which an adequate vitamin D status can reduce the risk of osteoporotic hip fractures. Thus, this project has great potential to improve community health by being able to recommend vitamin D supplementation made on the basis of maintaining normal bone cell function with psarticular reference to modulating bone resorption.Read moreRead less
Functional Dissection Of The Malaria RhopH Complex And Its Contribution To New Permeation Pathways
Funder
National Health and Medical Research Council
Funding Amount
$604,718.00
Summary
The ability of Plasmodium to invade and remodel its host erythrocyte are the most significant contributors to its ability to cause the disease malaria. This project aims to understand how proteins secreted from a specialized rhoptry organelle during erythrocyte invasion help Plasmodium to remodel the erythrocyte so that the parasite can gain access to the vital nutrients it requires for survival. This research will validate whether drugs targeting the rhoptry proteins are viable drug targets.
Defining The Apoptotic And Therapeutic Activities Of Histone Deacetylase Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$694,627.00
Summary
HDAC inhibitors (HDACi) are new chemotherapeutic drugs that kill tumors cells through a cell suicide process called apoptosis. We have used a mouse model of human blood cancers to show that these inhibitors can be used safely to severely limit the growth and spread of blood cancers. HDACi have the ability to inhibit multiple different target proteins (HDACs) and we aim to identify the key HDACs that cancer cells require to remain viable. Such information will lead to a more targeted or rational ....HDAC inhibitors (HDACi) are new chemotherapeutic drugs that kill tumors cells through a cell suicide process called apoptosis. We have used a mouse model of human blood cancers to show that these inhibitors can be used safely to severely limit the growth and spread of blood cancers. HDACi have the ability to inhibit multiple different target proteins (HDACs) and we aim to identify the key HDACs that cancer cells require to remain viable. Such information will lead to a more targeted or rational approach to chemotherapy using HDACi.Read moreRead less