Mitochondrial Quality Control In Parkinson’s Disease: The Molecular Mechanisms Of PINK1 And Parkin
Funder
National Health and Medical Research Council
Funding Amount
$558,721.00
Summary
Parkinson’s disease is a degenerative disorder of the central nervous system in which the underlying cause is mostly unknown. To pave the way to a better understanding of what goes wrong, this study will investigate the function of PINK1 and Parkin, two genes that are mutated in inherited forms of the disease that play important roles in maintaining cellular health. The results of this study will be used in exploring new therapeutic targets for the treatment of Parkinson’s disease symptoms.
Biochemical Investigation Of Ubiquitination By The Fanconi Anaemia Pathway
Funder
National Health and Medical Research Council
Funding Amount
$603,447.00
Summary
Fanconi anaemia is an inherited disorder with greatly elevated risk of leukaemia and cancers. The causal genes are ‘tumour suppressors’ that protect us from cancer by a complex function in repair of damage to our DNA. This study aims to understand how this DNA repair function protects us from cancer, and may influence some forms of new forms of cancer treatment.
How Burkholderia Pseudomallei Subverts Host Ubiquitination And Autophagy Pathways
Funder
National Health and Medical Research Council
Funding Amount
$472,260.00
Summary
Burkholderia pseudomallei is a bacterial organism found in soil and water that is the causative agent of melioidosis, a serious invasive disease of humans and animals occurring in tropical areas including northern Australia. Mortality is high owing to only limited treatment options being available. By defining the molecular mechanisms how B. pseudomallei evades removal from infected cells, we aim to identify specific bacterial targets that may form the basis of future prevention strategies.
Legionella bacteria are the major cause of Legionnaire’s Disease, a common form of acute pneumonia. Here we will study how the bacteria avoid killing in human cells by establishing an intracellular niche that is sequestered from the normal host cell defence pathways. In particular we hope to understand how the bacteria regulate a major protein modification pathway called ubiquitination.
Defining The Role Of The Ubiquitin Protein Ligase Nedd4 In Vascular Development.
Funder
National Health and Medical Research Council
Funding Amount
$702,166.00
Summary
Blood and lymphatic vessels are vital components of the cardiovascular system. Abnormalities in the growth and development of these vessels are associated with human disorders including cancer and cardiovascular disease. The focus of this application is to characterise the role of the ubiquitin protein ligase Nedd4 in vascular development, with the aim of identifying targets to which novel therapeutics for the treatment of blood and lymphatic vascular diseases could be generated.
Nedd4-2: A New Player In Polycystic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$671,995.00
Summary
Polycystic kidney disease (PKD) is a life threatening disorder affecting over 12 million people worldwide. This project is based on our discovery of a new gene that controls PKD. Using kidney specific gene knockout, biochemical and cellular approaches we will now address how this gene controls PKD. The results from this study will lead to better understanding of the underlying mechanisms that cause PKD, thus providing possible new targets for therapeutic interventions.
Host-virus Protein Complexes In The Immune System Response To Influenza
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
This proposal will investigate the inhibition of the human immune response by viruses. Specifically, an enzyme, TRIM25, which ubiquitinates proteins important for signalling the viral immune response has recently been shown to be inhibited by the non-structural influenza protein NS1. The mechanism of this inhibition is unknown and is thus the subject of this project.
Tipping The Inflammatory Response Of TNF In Favour Of Death
Funder
National Health and Medical Research Council
Funding Amount
$660,403.00
Summary
Cancer cells promote their own growth by exploiting the body’s natural defence. This natural defence is termed inflammation and cancer cells utilise inflammation to grow and metastasise. We have identified two exciting proteins that are required for cancer cells to stay alive. Under conditions that drive inflammation, if we remove these proteins cancer cells now activate their death signals and die. Our discovery provides new opportunities on fundamental ways by which cancer cells can be killed.
The body tightly controls when and where proteins are made. Likewise once a protein has performed its function, it must be removed. Targeted proteolysis serves to reset the cell so that it can respond anew to stimuli that trigger growth and cell development. The Siah proteins are a family of proteins that control the turnover of other proteins. Siah proteins are remarkably highly conserved in evolution, and counterparts of the human proteins can be found in fruitflies, worms and plants. There ar ....The body tightly controls when and where proteins are made. Likewise once a protein has performed its function, it must be removed. Targeted proteolysis serves to reset the cell so that it can respond anew to stimuli that trigger growth and cell development. The Siah proteins are a family of proteins that control the turnover of other proteins. Siah proteins are remarkably highly conserved in evolution, and counterparts of the human proteins can be found in fruitflies, worms and plants. There are three different types of Siah protein in mice and this study investigates the function of the each protein by creating mice that lack one or more of these proteins. Our work to date has revealed that the Siah genes are involved in growth and fertility of mammals. The genes are also important for cell division, which implicates them in proliferative diseases such as cancer.Read moreRead less