Neurons are highly compartmentalized cell-types. In neurodegenerative diseases such as Alzheimer's disease, the protein Tau that serves a distinct function in one cellular compartment (the axon) accumulates in a massively phosphorylated form elsewhere (somatodendritic compartments and their spines) which is believed to impair neuronal functions. We will investigate how Tau is distributed in health and disease, and determine how this distribution is regulated.
Melanoma Resistance To Combination BRAF And MEK Inhibition Is Driven By Reprogramming Of MAPK Signaling
Funder
National Health and Medical Research Council
Funding Amount
$745,082.00
Summary
Until recently, patients with metastatic melanoma were treated with single agent chemotherapy drugs that produce response rates of less than 10%. New drugs targeting the mitogen activated protein kinase (MAPK) pathway have now shown significant activity, but nearly all patients treated with these new inhibitors eventually develop resistance and progress. This project utilises patient tumour samples to examine the mechanisms of resistance and ways of enhancing the targeted inhibition of the MAPK ....Until recently, patients with metastatic melanoma were treated with single agent chemotherapy drugs that produce response rates of less than 10%. New drugs targeting the mitogen activated protein kinase (MAPK) pathway have now shown significant activity, but nearly all patients treated with these new inhibitors eventually develop resistance and progress. This project utilises patient tumour samples to examine the mechanisms of resistance and ways of enhancing the targeted inhibition of the MAPK signaling cascade.Read moreRead less
New drugs targeting the immune system have dramatically improved the survival of melanoma patients. Nevertheless, 30-40% of patients responding to these new inhibitor will develop drug resistance. This project utilizes patient tumour samples to examine the mechanisms of acquired resistance to immune checkpoint inhibitors. This information will accelerate the identification of novel combination therapies to improve patient outcomes.
Site-specific Tau Phosphorylation To Treat And Understand Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$943,902.00
Summary
Alzheimer’s disease (AD) is the most common form of dementia. Unfortunately, current therapies are ineffective. Our laboratory has made an important contribution to understanding the events that lead to brain cell malfunction in AD. I recently found a novel concept that changes the view of AD completely. In the next 3 years, I aim to develop therapeutic tools based on this novel concept and find out more about how it can protect brains from AD.
Finding The Missing Katanin Required For Male Fertility
Funder
National Health and Medical Research Council
Funding Amount
$417,214.00
Summary
Microtubules are a key element of all cells, including in the male germ line. In this project we will define the function of the microtubule severing protein KATNA1 in male fertility. This will be achieved using a unique model and state-of-the-art technologies. This project will have immediate relevance to the 1 in 20 Australian men who suffer from infertility but will also inform KATNA1 function in the many other tissues where KATNA1 is produced.
NOVEL MECHANISMS UNDERLYING THE SPREADING OF TAU PATHOLOGY IN ALZHEIMER’S DISEASE AND OTHER TAUOPATHIES
Funder
National Health and Medical Research Council
Funding Amount
$640,106.00
Summary
Alzheimer’s disease and related dementias affect 230,000 people in Australia, with numbers expected to grow to three times that by 2050. The direct costs for health and residential care alone already exceed $6.6 billion per annum. The underlying pathomechanisms and the processes that drive the progression of neurodegeneration in these devastating disorders remain largely unknown. Here, we will identify novel therapeutic targets and assist in developing therapies for yet incurable diseases.
Targeting Post-synaptic Tau To Treat Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,686,311.00
Summary
We have previously identified post-synaptic tau as being critical in mediating toxicity in Alzheimer's disease brains. This project aims at understanding the exact underlying molecular mechanisms and, more importantly, developing novel drugs to block early toxicity that initiates cascades that eventually lead to brain atrophy and dementia. To achieve this aim, this project will generate and utilize models of Alzheimer's disease in combination with a broad range of latest analytical tools.
Protein Phosphatase 2A Methylation: Regulation And Functional Significance For Tauopathies
Funder
National Health and Medical Research Council
Funding Amount
$470,713.00
Summary
Clinical studies have revealed that low blood levels of the vitamin folate are a risk factor for cognitive impairment, depression and dementia, which are prevalent in the elderly. Deregulation of the protein tau is a key event in Alzheimer’s disease pathogenesis. This project will utilize cell culture and aged mouse models to determine how alterations in folate status and deregulation of protein phosphatase 2A affect the regulation of tau and other key brain processes that become altered in Alzh ....Clinical studies have revealed that low blood levels of the vitamin folate are a risk factor for cognitive impairment, depression and dementia, which are prevalent in the elderly. Deregulation of the protein tau is a key event in Alzheimer’s disease pathogenesis. This project will utilize cell culture and aged mouse models to determine how alterations in folate status and deregulation of protein phosphatase 2A affect the regulation of tau and other key brain processes that become altered in Alzheimer’s disease.Read moreRead less
DISCOVERY OF GENES THAT PROTECT AGAINST TAU-INDUCED NEUROPATHOLOGY
Funder
National Health and Medical Research Council
Funding Amount
$921,764.00
Summary
Dementia incurs $5 billion of direct health costs, affects 300,000 Australians and its incidence is increasing. New treatments are urgently needed. Dementia is associated with tau protein aggregates in the brain. Finding genes that prevent symptoms caused by tau aggregates will help develop new treatments, but identifying such genes has been very difficult and expensive. We will use our world-leading resource to revolutionize gene discovery and identify genes that can protect against dementia.
Trafficking Mechanisms Governing Receptor Availability For Signalling
Funder
National Health and Medical Research Council
Funding Amount
$526,978.00
Summary
Receptors on the cell surface allow cells to respond to their environment. We have recently discovered a new pathway for controlling the amount of receptors displayed on the cell surface, errors within which will lead to defects in development and diseases like cancer. We are studying how this new pathway controls the balance between how much receptors are destroyed after being activated and how much are recycled back for re-use.