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
Discovery Early Career Researcher Award - Grant ID: DE150100091
Funder
Australian Research Council
Funding Amount
$341,000.00
Summary
Traffic on DNA: interplay between RNA polymerases and DNA-bound proteins. The DNA inside the cell is not just a repository of information, but is an active player in how that information is used. Proteins bind to defined locations on the DNA to control which genes are active, and genes are expressed by RNA polymerases that track along the DNA. Collisions between RNA polymerases and DNA-bound proteins can remove the proteins or block the polymerase. How can these essential processes safely coexis ....Traffic on DNA: interplay between RNA polymerases and DNA-bound proteins. The DNA inside the cell is not just a repository of information, but is an active player in how that information is used. Proteins bind to defined locations on the DNA to control which genes are active, and genes are expressed by RNA polymerases that track along the DNA. Collisions between RNA polymerases and DNA-bound proteins can remove the proteins or block the polymerase. How can these essential processes safely coexist on the DNA? The project aims to integrate systematic experiments using well-defined genetic components and mathematical modelling to understand the 'design' features of DNA and proteins that minimise these traffic problems. A better understanding could inform new strategies for manipulation of gene expression.Read moreRead less
Identification of Biological pathways regulated by circular RNAs. Circular RNAs (circRNAs) are a, recently discovered molecule. circRNAs are highly abundant and expressed in a tissue and disease specific manner. Yet, currently the understanding of how circRNAs regulate biological processes is very poor. This project aims to use pooled shRNA libraries to screen a large panel of cell lines and systematically identify cellular activities that are regulated by circRNAs. The expected outcome of this ....Identification of Biological pathways regulated by circular RNAs. Circular RNAs (circRNAs) are a, recently discovered molecule. circRNAs are highly abundant and expressed in a tissue and disease specific manner. Yet, currently the understanding of how circRNAs regulate biological processes is very poor. This project aims to use pooled shRNA libraries to screen a large panel of cell lines and systematically identify cellular activities that are regulated by circRNAs. The expected outcome of this study will be a catalogue of functionally active circRNAs. Over the past decades, the wealth of knowledge on the function of linear mRNAs has had a significant impact on medicine and agriculture. Similarly understanding how circRNAs regulate cellular activities may have an analogous impact on humans.Read moreRead less
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
Defining how molecular switches program cell identity during development. Aims: This project aims to investigate how molecular switches known as transcription factors, work together to turn genes on or off to program cell identity during development.
Significance: This project expects to generate new knowledge in the area of genetics and developmental biology using collaborative, cutting edge technologies.
Outcomes: Expected outcomes of this project include the identification of new genes impor ....Defining how molecular switches program cell identity during development. Aims: This project aims to investigate how molecular switches known as transcription factors, work together to turn genes on or off to program cell identity during development.
Significance: This project expects to generate new knowledge in the area of genetics and developmental biology using collaborative, cutting edge technologies.
Outcomes: Expected outcomes of this project include the identification of new genes important for programming the identity of cells that comprise our blood vessels, lymphatic vessels and circulating blood cells.
Benefits: Data generated will underpin the development of approaches to program/reprogram stem cells to produce mature cells for transplantation or tissue engineering purposes ex vivo.Read 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
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
Improving water market outcomes through a better understanding of market behaviour. The issue of water resources and their sustainable use is probably the most important issue facing the rural sector. The water reform process and its aim to secure water for the environment will cause economic and social pain and result in structural change within the irrigation sector. Properly functioning water markets will play an instrumental role in facilitating this process by providing water for the envir ....Improving water market outcomes through a better understanding of market behaviour. The issue of water resources and their sustainable use is probably the most important issue facing the rural sector. The water reform process and its aim to secure water for the environment will cause economic and social pain and result in structural change within the irrigation sector. Properly functioning water markets will play an instrumental role in facilitating this process by providing water for the environment and allowing water to move between competing resources. This study will enable policy makers and water managers to optimise the positive outcome of water markets and increase the likely success of programs to purchase environmental water.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE160100620
Funder
Australian Research Council
Funding Amount
$378,000.00
Summary
Mechanisms of controlled gene expression in cells and organisms. The goal of this project is to reveal the nature of a cellular mechanism that has a major influence on gene expression in all eukaryotic cells. How gene expression is controlled is of fundamental importance to all life forms. The project plans to develop molecular tools that enable the visualisation and interrogation of this gene regulatory mechanism in live cells, tissues and whole organisms. The outcomes are anticipated to lead t ....Mechanisms of controlled gene expression in cells and organisms. The goal of this project is to reveal the nature of a cellular mechanism that has a major influence on gene expression in all eukaryotic cells. How gene expression is controlled is of fundamental importance to all life forms. The project plans to develop molecular tools that enable the visualisation and interrogation of this gene regulatory mechanism in live cells, tissues and whole organisms. The outcomes are anticipated to lead to an essential understanding of how cells respond to physiological and environmental cues by coordinating changes in gene expression, and to provide potential avenues towards manipulation for pharmaceutical, agricultural and biotechnology purposes.Read moreRead less
Investigation of the fundamental roles of class Ib MHC (major histocompatibility complex) molecules in immunity. The proposed research program, using laboratory-based and synchrotron-based radiation, will provide insight into the roles of a poorly understood class of immune molecules. This will improve our understanding of the regulation of immunity, and the knowledge gained will increase Australia's international research profile.