A study of the nongenomic action of Vitamin D: proposed role of the nuclear VDR and downstream signalling molecules. Vitamin D (1,25D) activates genes in the nucleus through the vitamin D receptor (VDR). 1,25D can also elicit rapid responses at the plasma membrane. This action is critical to the activation of nuclear genes. We hypothesise that a proportion of the nuclear VDR is located at the plasma membrane where it stimulates downstream signalling molecules eg Ras, ERK1/2 and ERK5. We plan to ....A study of the nongenomic action of Vitamin D: proposed role of the nuclear VDR and downstream signalling molecules. Vitamin D (1,25D) activates genes in the nucleus through the vitamin D receptor (VDR). 1,25D can also elicit rapid responses at the plasma membrane. This action is critical to the activation of nuclear genes. We hypothesise that a proportion of the nuclear VDR is located at the plasma membrane where it stimulates downstream signalling molecules eg Ras, ERK1/2 and ERK5. We plan to explore this hypothesis and to identify the signalling molecules. We will also investigate our novel finding that a specific Ras isoform is involved in ERK5 activation. The work will provide new information on signalling pathways.Read moreRead less
Targeting MicroRNA-driven Mesenchymal To Epithelial Transition To Suppress Prostate Cancer Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$741,831.00
Summary
Prostate cancer kills ~3,000 men per year in Australia. The development of metastasis is the major cause of prostate cancer-associated death and has limited treatment options. In this study, we will characterise the role of a group of molecules, termed microRNAs, in prostate cancer metastasis. We will also test whether targeting microRNAs using novel drugs termed antagomiRs is an effective strategy to inhibit metastasis and thereby improve prostate cancer mortality.
Structure And Function Of Antimicrobial Therapies And Their Interaction With Upper Respiratory Biofilms
Funder
National Health and Medical Research Council
Funding Amount
$320,891.00
Summary
Bacterial infections of the upper respiratory tract are a major public health problem affecting millions of Australians. Commonly prescribed antibiotics are often not able to eradicate all bacteria as the bacteria often reside in a protective, self-produced gel-like matrix known as biofilm. This Fellowship aims to unravel the interaction of modern anti-infective therapeutics with the biofilm for the development of the next generation of safe and efficacious anti-biofilm strategies.
The Role Of UPF3B And Nonsense Mediated MRNA Decay Surveillance In The Pathology Of Intellectual Disability.
Funder
National Health and Medical Research Council
Funding Amount
$789,954.00
Summary
Proper functioning of the nonsense mediated mRNA decay (NMD or 'mRNA police') is crucial for any cell to ensure normal development and function. When NMD is compromised the outcome is learning and memory problems, autism or schizophrenia. Under this project we study malfunctioning NMD using stem and neuronal cells derived from patients' skin cells. Some of the affected genes might be considered for therapeutic interventions. NMD is relevant to 1000s of human disorders and as such it is of fundam ....Proper functioning of the nonsense mediated mRNA decay (NMD or 'mRNA police') is crucial for any cell to ensure normal development and function. When NMD is compromised the outcome is learning and memory problems, autism or schizophrenia. Under this project we study malfunctioning NMD using stem and neuronal cells derived from patients' skin cells. Some of the affected genes might be considered for therapeutic interventions. NMD is relevant to 1000s of human disorders and as such it is of fundamental importance.Read moreRead less
About one in eight known genetic disorders involve DNA alteration that activates a cellular quality control mechanism that disables the affected gene. This mechanism is more efficient in some individuals than others. It can influence disease outcomes and severity. We will engineer and apply tools and models to measure and manipulate this crucial cellular mechanism. This will allow us to predict disease severity as well as to intervene where a manipulation of this mechanism will be beneficial.
Regulatory mechanisms for calcium release-activated calcium channels. Store-operated calcium channels play a central role in the functions of all animal cells. They participate in generating the cellular responses to hormones, growth factors and other physiological stimuli. The aims of this project are to elucidate the mechanisms that regulate the activity of store-operated channels and how their properties can be modulated by different pharmacological agents. Using chiefly the techniques of ele ....Regulatory mechanisms for calcium release-activated calcium channels. Store-operated calcium channels play a central role in the functions of all animal cells. They participate in generating the cellular responses to hormones, growth factors and other physiological stimuli. The aims of this project are to elucidate the mechanisms that regulate the activity of store-operated channels and how their properties can be modulated by different pharmacological agents. Using chiefly the techniques of electrophysiology and molecular biology we expect to learn the fundamental mechanisms that modulate the opening and closing of store-operated calcium channels and to gain an important information that can be used for determining the molecular structure of these channelsRead moreRead less
Second messenger-activated calcium channels in liver cells. This project concerns second messenger-activated calcium channels, part of the family of hormone-activated calcium channels which are essential to the functions of all animal cells. The aims are to elucidate the properties of a novel "large conductance" Ca2+ channel (using maitotoxin as an artificial activator), an inositol 1,4,5-trisphosphate-activated calcium channel, and the calcium channel formed by the transient receptor potential ....Second messenger-activated calcium channels in liver cells. This project concerns second messenger-activated calcium channels, part of the family of hormone-activated calcium channels which are essential to the functions of all animal cells. The aims are to elucidate the properties of a novel "large conductance" Ca2+ channel (using maitotoxin as an artificial activator), an inositol 1,4,5-trisphosphate-activated calcium channel, and the calcium channel formed by the transient receptor potential-1 (TRP-1) protein in hepatocytes. The electrophysiological properties, mechanisms of activation and intracellular trafficking of the channels will be investigated. It is anticipated the results will provide basic information on the physiological functions of second messenger-activated calcium channels. This will benefit the understanding of liver function, hepatotoxicity in animals, animal production and the development of pharmaceuticals in animal husbandary.Read moreRead less
Identification Of Genes For X-linked Mental Retardation.
Funder
National Health and Medical Research Council
Funding Amount
$675,228.00
Summary
We propose to identify novel heritable causes of intellectual disability using 22 large and well-characterised families from Australia. In these families we have refined the location of the genetic defect to the chromosome X and excluded the contribution of all so far known genes. We will achieve this using the technology of massive parallel sequencing. At the completion of the project we will have identified novel causes of intellectual disability and devised tests to identify them.
The bHLH.PAS transcription factors: Determinants of dimerization specificity and high affinity DNA binding. This program of fundamental research will advance our knowledge of the way essential proteins act to correctly regulate critical biological processes. A detailed understanding of these processes at the molecular level has the potential to contribute to the design of pharmaceutical compounds to assist in the treatment of diseases such as ischaemia, myocardial infarction and tumour progress ....The bHLH.PAS transcription factors: Determinants of dimerization specificity and high affinity DNA binding. This program of fundamental research will advance our knowledge of the way essential proteins act to correctly regulate critical biological processes. A detailed understanding of these processes at the molecular level has the potential to contribute to the design of pharmaceutical compounds to assist in the treatment of diseases such as ischaemia, myocardial infarction and tumour progression. The work will contribute to the training of one or more graduate students in a technologically advancing and internationally competitive field.Read moreRead less