Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0561030
Funder
Australian Research Council
Funding Amount
$441,100.00
Summary
Developmental Imaging Facility. This application seeks to establish a facility to undertake expression profiling in vertebrate tissues on a genomic scale and at the highest resolution. Undertaking large scale projects of this nature requires specialised robotics and dedicated infrastructure for microscopy and tissue preparation. This facility will be the first of its type in Australia will permit researchers to perform genomic scale in situ screens, many as part of large international initiative ....Developmental Imaging Facility. This application seeks to establish a facility to undertake expression profiling in vertebrate tissues on a genomic scale and at the highest resolution. Undertaking large scale projects of this nature requires specialised robotics and dedicated infrastructure for microscopy and tissue preparation. This facility will be the first of its type in Australia will permit researchers to perform genomic scale in situ screens, many as part of large international initiatives in developmental and cellular biology. This large-scale, high-resolution expression profiling infrastructure is required to maintain international competitiveness and will dramatically improve our gene discovery, functional assessment and understanding of vertebrate development.Read moreRead less
Organisation, expression and diversity of the sub-telomeric regions of the ancient eukaryote, Giardia duodenalis. We propose to extend our findings on the extreme plasticity of the structure and organisation of the sub-telomeric region of the complete genome of Giardia by more extensive chromosome walking, and comparison of different isolates. These regions are subject to gene conversion, transcriptional silencing, gene mobility, recombination, variable surface protein expression, subtelomeric i ....Organisation, expression and diversity of the sub-telomeric regions of the ancient eukaryote, Giardia duodenalis. We propose to extend our findings on the extreme plasticity of the structure and organisation of the sub-telomeric region of the complete genome of Giardia by more extensive chromosome walking, and comparison of different isolates. These regions are subject to gene conversion, transcriptional silencing, gene mobility, recombination, variable surface protein expression, subtelomeric instability and the insertion of transposable elements, a dynamic balance between structural conservation and rapid evolution. This is a rare opportunity to understand the forces at work in moulding eukaryotic sub-telomeric sequences because Giardia is not constrained by sexual homogenisation and the dynamic variability is retained.Read moreRead less
The sulfate anion transporter gene, Sat1: physiology, regulation and developmental expression. Sulfate is an essential nutrient for cell growth and survival. The kidneys and liver help regulate sulfate levels in the body, by yet unknown mechanisms. Recently, we cloned a gene, Sat1, expressed in mouse liver and kidneys, which may be responsible for body sulfate maintenance. In this study, we will determine the physiological importance of Sat1 in cell growth/survival and in controlling body sulfa ....The sulfate anion transporter gene, Sat1: physiology, regulation and developmental expression. Sulfate is an essential nutrient for cell growth and survival. The kidneys and liver help regulate sulfate levels in the body, by yet unknown mechanisms. Recently, we cloned a gene, Sat1, expressed in mouse liver and kidneys, which may be responsible for body sulfate maintenance. In this study, we will determine the physiological importance of Sat1 in cell growth/survival and in controlling body sulfate levels. We will generate and characterise a Sat1 lacking mouse, study its expression during development and its effects on other genes. We will elucidate how body sulfate levels are maintained and its importance in cell growth/development.Read moreRead less
Evolution of nervous system patterning processes: characterisation of homologs of key Drosophila regulatory genes from the coral Acropora. Defining the common mechanisms of nervous system development is one of the major goals of modern biology, but is presently being addressed largely by comparisons between a few very advanced (and therefore specialised) animals. Comparative data from a lower animal is urgently needed, and will clarify many aspects of nervous system evolution and development. Th ....Evolution of nervous system patterning processes: characterisation of homologs of key Drosophila regulatory genes from the coral Acropora. Defining the common mechanisms of nervous system development is one of the major goals of modern biology, but is presently being addressed largely by comparisons between a few very advanced (and therefore specialised) animals. Comparative data from a lower animal is urgently needed, and will clarify many aspects of nervous system evolution and development. The pioneering work carried out on Acropora in this laboratory suggests that it is perhaps the best choice currently available for this purpose. This project will use Acropora to address fundamental questions about the evolution of nervous system developmental processes.Read moreRead less
Molecular genetic analyses of trinucleotide repeat expansions. Several neuronal diseases like Huntington's disease, Frederick's ataxia and fragile X syndrome are caused by expansion of trinucleotide repeat sequences in the deoxyribonucleic acid (DNA). These diseases show progressive severity in subsequent generations. Here we use a simple plant model with a very similar DNA mutation to study the genetic basis of repeat expansions over several generations across populations. This proposal will im ....Molecular genetic analyses of trinucleotide repeat expansions. Several neuronal diseases like Huntington's disease, Frederick's ataxia and fragile X syndrome are caused by expansion of trinucleotide repeat sequences in the deoxyribonucleic acid (DNA). These diseases show progressive severity in subsequent generations. Here we use a simple plant model with a very similar DNA mutation to study the genetic basis of repeat expansions over several generations across populations. This proposal will improve our mechanistic understanding of genetic diseases in populations. In addition, this proposal is expected to lead to identification of potential targets and technologies that would be of interest to Australian industry.Read moreRead less
A Genomic analysis of macrophage differentiation: Epigenetic factors that determine transcriptional choices in a lineage dependant manner. Our genetic information is fundamental to who we are, how we develop, & how we age. This project will build the research capacity of Australia's genome sciences, providing an analytical framework to describe & study the many products expressed from any single gene and to assess the function of genetic variation & test genome regulatory events. An immediate ou ....A Genomic analysis of macrophage differentiation: Epigenetic factors that determine transcriptional choices in a lineage dependant manner. Our genetic information is fundamental to who we are, how we develop, & how we age. This project will build the research capacity of Australia's genome sciences, providing an analytical framework to describe & study the many products expressed from any single gene and to assess the function of genetic variation & test genome regulatory events. An immediate outcome is a better understanding of the regulation of our immune system. This approach will fuel the discovery of new signalling molecules & their effects on a population of cells, & likewise provides a novel approach to study the dysregulation of cell signalling pathways.Read moreRead less
The sponge genome project and the evolution of multicellularity: using comparative genomics and developmental biology to reconstruct the first animals. Recently the entire genome from a living fossil - a sponge from the Great Barrier Reef - was sequenced (jointly supported by the ARC and US Department of Energy). As this genome is assembled and analysed, many of the fundamental biological processes that underlie the construction and evolution of all animals, including humans, will be revealed. ....The sponge genome project and the evolution of multicellularity: using comparative genomics and developmental biology to reconstruct the first animals. Recently the entire genome from a living fossil - a sponge from the Great Barrier Reef - was sequenced (jointly supported by the ARC and US Department of Energy). As this genome is assembled and analysed, many of the fundamental biological processes that underlie the construction and evolution of all animals, including humans, will be revealed. In addition, sponge genomics will fuel innovations in medicine and biotechnology. Specifically, sponges are renowned for their capacity to synthesise bioactive compounds used in drug development, and high-grade silica used for semi-conductor construction. This project will identify the gene networks controlling these biosynthetic processes.Read moreRead less
Pre-clinical evaluation of snake venom proteins with therapeutic potential. Australia harbors some of the most toxic snakes in the world. Their venoms contain a range of substances that are designed to rapidly immobilize and kill their prey. These include agents that lead to enhanced blood clotting; excess bleeding. We have isolated and characterized a large number of the components involved over the last several years. The aim here is to carry out pre-clinical trials in animal models to test th ....Pre-clinical evaluation of snake venom proteins with therapeutic potential. Australia harbors some of the most toxic snakes in the world. Their venoms contain a range of substances that are designed to rapidly immobilize and kill their prey. These include agents that lead to enhanced blood clotting; excess bleeding. We have isolated and characterized a large number of the components involved over the last several years. The aim here is to carry out pre-clinical trials in animal models to test the efficacy of three proteins as anti-bleeding agents and investigate several other novel components. The ultimate outcome will be the development of novel drugs that will have application in the treatment of human disorders. Read moreRead less
To investigate the role of the protein kinase SMG-1 in the stress response. This project is included in the designated priority area of research Promoting and Maintaining Good Health and Ageing Well. It represents a mouse model to assist in the study of human disease. It is the first mouse model for SMG-1, a protein kinase that protects against a variety of different forms of stress. The strength of the model is that it can be combined with other mouse models to interrogate and elucidate the eve ....To investigate the role of the protein kinase SMG-1 in the stress response. This project is included in the designated priority area of research Promoting and Maintaining Good Health and Ageing Well. It represents a mouse model to assist in the study of human disease. It is the first mouse model for SMG-1, a protein kinase that protects against a variety of different forms of stress. The strength of the model is that it can be combined with other mouse models to interrogate and elucidate the events occurring in different pathways for stress. The expectation is that ground-breaking data will be generated with this model providing scientific leadership on the role of this protein. It will also assist in establishing new collaborations.Read moreRead less
The function of menin in mammalian development. This project aims to determine the role of a ubiquitous transcriptional co-regulator, menin, in mammalian development. Mice that lack menin through targeted deletion of the gene die during embryogenesis, but the cause is unknown, although is likely to be due to the abnormal expression of genes usually regulated by this factor. We will determine which genes are inappropriately expressed and responsible for the accompanying developmental defects. Thi ....The function of menin in mammalian development. This project aims to determine the role of a ubiquitous transcriptional co-regulator, menin, in mammalian development. Mice that lack menin through targeted deletion of the gene die during embryogenesis, but the cause is unknown, although is likely to be due to the abnormal expression of genes usually regulated by this factor. We will determine which genes are inappropriately expressed and responsible for the accompanying developmental defects. This knowledge will help us understand the process of development in mammals, including birth defects in humans.Read moreRead less