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
Adaptive Evolution of BRCA1 in Ancestral Mammals. This project investigates adaptive evolution of BRCA1 in the early radiation of mammals. We will test the hypothesis that the evolution of mammary glands and X chromosome inactivation has resulted in modification of the BRCA1 protein sequence as it aquired new roles in these processes. We will also investigate the importance of these changes inducing compensatory changes in other parts of the protein.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775778
Funder
Australian Research Council
Funding Amount
$196,000.00
Summary
A microarray platform for gene expression analysis and genotyping in biological systems. This technology has substantial benefits for basic science and biotechnology. The ability to rapidly study changes in gene expression in living organisms will benefit agriculture, animal and biomedical science and biotechnology. The Affymetrix platform creates opportunities for new avenues of research, such as studying epigenetic (DNA and protein modifications) mechanisms in development, ageing and disease. ....A microarray platform for gene expression analysis and genotyping in biological systems. This technology has substantial benefits for basic science and biotechnology. The ability to rapidly study changes in gene expression in living organisms will benefit agriculture, animal and biomedical science and biotechnology. The Affymetrix platform creates opportunities for new avenues of research, such as studying epigenetic (DNA and protein modifications) mechanisms in development, ageing and disease. The project falls within the designated national research priority areas of 'promoting and maintaining good health" and the priority goals of "a healthy start to life", "aging well", "aging productively" and "preventative health care."Read moreRead less
Discovery of novel microRNA biogenesis and functional components. Discovery of novel microRNA components will provide new strategies for confronting a diverse array of challenges Australia faces, such as the increasing rates of certain cancers in our population, to stresses on our crop plants faced with environmental changes. The biological mechanisms underlying these disparate problems are unified by microRNA involvement in many instances. By finding microRNA controlling factors common to all h ....Discovery of novel microRNA biogenesis and functional components. Discovery of novel microRNA components will provide new strategies for confronting a diverse array of challenges Australia faces, such as the increasing rates of certain cancers in our population, to stresses on our crop plants faced with environmental changes. The biological mechanisms underlying these disparate problems are unified by microRNA involvement in many instances. By finding microRNA controlling factors common to all higher organisms, we expect our community will benefit from the increased knowledge base that will help our researchers adopt new strategies in fighting diseases and improving our agricultural industry.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
An RNA interference based genetic screen for novel epigenetic modifiers involved in mammalian X inactivation. All the information required to form an adult human is contained in the DNA of the fertilized egg. Development is achieved by a complex orchestration of genes being switched on and off, controlled by proteins called epigenetic modifiers. Sometimes this goes awry, leading to disease. Despite their vital role, only around ten percent of the potential epigenetic modifiers have been characte ....An RNA interference based genetic screen for novel epigenetic modifiers involved in mammalian X inactivation. All the information required to form an adult human is contained in the DNA of the fertilized egg. Development is achieved by a complex orchestration of genes being switched on and off, controlled by proteins called epigenetic modifiers. Sometimes this goes awry, leading to disease. Despite their vital role, only around ten percent of the potential epigenetic modifiers have been characterized in humans, making it impossible to interpret how they work together, or when they fail. We will develop a novel screen-based technology to find hundreds more true epigenetic modifiers. This technology will aid us and other Australian scientists to understand the role of epigenetics in normal development and disease, ultimately leading to better public health.Read moreRead less
Transcriptional and epigenetic regulation of terminal lymphocyte differentiation and alterations of the same that lead to leukemia. In the developed world infection diseases are the number three killer behind heart disease and cancer, and huge financial effort is put into treatment and prevention. Despite this, results have often been disappointing. One cause of these poor outcomes is the lack of knowledge of how effective immune responses are generated. This project aims to better understand th ....Transcriptional and epigenetic regulation of terminal lymphocyte differentiation and alterations of the same that lead to leukemia. In the developed world infection diseases are the number three killer behind heart disease and cancer, and huge financial effort is put into treatment and prevention. Despite this, results have often been disappointing. One cause of these poor outcomes is the lack of knowledge of how effective immune responses are generated. This project aims to better understand the processes that control the generation of protective lymphocytes. It will deliver information that may enable a more targeted approach to vaccine-development and treatments of infections. As defective differentiation can also be a cause of leukemia it may also lead to targets of cancer treatment.Read moreRead less
The role of the neuronal Hu proteins in the regulation of the BMP signalling pathway. We aim to understand the critical decision of a neural progenitor to commit to becoming a neuron. The BMP signalling pathway is central in this decision. Neural progenitors appear to become insensitive to BMP signals, and this lack of signalling leads to neuronal differentiation. We hypothesise that neuronal identity is regulated by an unusual genetic switch- the translational regulation by the neuronal Hu pr ....The role of the neuronal Hu proteins in the regulation of the BMP signalling pathway. We aim to understand the critical decision of a neural progenitor to commit to becoming a neuron. The BMP signalling pathway is central in this decision. Neural progenitors appear to become insensitive to BMP signals, and this lack of signalling leads to neuronal differentiation. We hypothesise that neuronal identity is regulated by an unusual genetic switch- the translational regulation by the neuronal Hu proteins of two proteins in the BMP pathway. Verification of a post-transcriptional regulatory mechanism for cell fate determination would be a major discovery, and may prompt investigation of how to harness the neuron-inducing function of the Hu proteins to address the therapeutic need for new neurons in neurologic diseases.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
Functional Analysis Of The P160 Myb-binding Protein - A Regulator Of Multiple Transcription Factors?
Funder
National Health and Medical Research Council
Funding Amount
$376,697.00
Summary
The c-myb gene is a key molecular regulator of normal blood cell production, but alterations to this gene can also lead to leukaemia. The protein (Myb) encode by the c-myb gene acts as a transcription factor, ie, it controls the activity of other genes. There is good evidence that interactions with other proteins can regulate the activity of Myb. Our laboratory has identified what we believe is one such protein - p160 - that binds to a part of Myb that reduces its activity, and thus that is like ....The c-myb gene is a key molecular regulator of normal blood cell production, but alterations to this gene can also lead to leukaemia. The protein (Myb) encode by the c-myb gene acts as a transcription factor, ie, it controls the activity of other genes. There is good evidence that interactions with other proteins can regulate the activity of Myb. Our laboratory has identified what we believe is one such protein - p160 - that binds to a part of Myb that reduces its activity, and thus that is likely to be responsible for regulating Myb. However, it has recently become apparent that p160 interacts with a number of other transcription factors in addition Myb. The primary aim of this project is to elucidate precisely how p160 interacts with Myb and what the consequences of this interaction are. A range of experimental approaches, which range from in vitro to genetic studies, will be employed to do this. We will test a specific role of p160 suggested by our preliminary studies - that of a transporter of transcription factors between the nucleus and the cytoplasm of the cell. Because of the wide range of transcription factors that p160 interacts with, its effects on the function of the cell are likely to be profound. For this same reason, it is difficult to specifically predict the possible medical-health implications of this work However, what we know to date is consistent with a role for p160 as a tumour suppressor gene. Moreover, parts of this project aim to generate genetic information and tools which will help in determining whether p160 does play such a role and generally, in identifying any other associations of p160 with particular diseases.Read moreRead less