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.
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
Elucidating The Role Of MiR-196 In Formation Of The Axial Skeleton
Funder
National Health and Medical Research Council
Funding Amount
$520,087.00
Summary
Exquisite regulation of gene expression is a fundamental principle underlying growth and development of an embryo as well as homeostasis in the adult. Following the identification of hundreds of microRNAs within the genome which act to modulate gene expression, the challenge and the goal of these studies, is to identify individual microRNAs which contribute significantly to bone formation in the developing embryo.
All cells in the body need to get their energy from somewhere, and the chemical basis of their energy supply varies depends on many factors, including their location and rate of cell division. We have found that an important population of white blood cells that control the character and magnitude of most immune responses appear to use an unusual source of their energy. If true this would provide a range of new opportunities to control the numbers and activities of these cells, a thereby control ....All cells in the body need to get their energy from somewhere, and the chemical basis of their energy supply varies depends on many factors, including their location and rate of cell division. We have found that an important population of white blood cells that control the character and magnitude of most immune responses appear to use an unusual source of their energy. If true this would provide a range of new opportunities to control the numbers and activities of these cells, a thereby control the character and magnitude of immune responses.Read moreRead less
Defining Ubiquitin Ligase Substrates: New Therapeutic Strategies In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$598,163.00
Summary
Current cancer therapies use drugs that target both tumor cells and rapidly growing normal cells – causing side effects and limiting effectiveness. Newer treatments aim to target molecules that are unique to tumor cells, leaving normal cells unharmed. This project will study a process that tags proteins for destruction by a cellular recycling system, which is often disrupted in cancer. This research will not only help us understand how cancer develops, but also identify new targets for therapy.