Mouse models for the identification of factors involved in muscle adaptation. The ability of muscle to adapt to meet functional demands is essential for mobility in normal daily life, in ageing well, in individuals with muscle diseases and nerve damage and in athletes. The ability of muscle to change its cellular composition is desirable for the livestock industry. Knowledge of how genes in muscle cells are regulated to adapt to demands has significant implications for public health and economic ....Mouse models for the identification of factors involved in muscle adaptation. The ability of muscle to adapt to meet functional demands is essential for mobility in normal daily life, in ageing well, in individuals with muscle diseases and nerve damage and in athletes. The ability of muscle to change its cellular composition is desirable for the livestock industry. Knowledge of how genes in muscle cells are regulated to adapt to demands has significant implications for public health and economic benefits. We have devised model systems that will allow us to identify the regulators of these genes in order to develop therapies to combat these changes in ageing and damaged muscle, to improve the quality of meat and optimise sport performance.Read moreRead less
A Structural And Functional Basis For The Regulation Of Gene Expression By Nuclear Retention Of RNA
Funder
National Health and Medical Research Council
Funding Amount
$504,097.00
Summary
The nuclear retention mechanism is a novel way used by cells to control which genes are made into proteins - a fundamental process for all diseases, particularly cancers. This project will employ cutting edge structural and proteomic techniques to determine the molecular details underpinning nuclear retention. These insights will be important for the development of new tissue-restricted gene therapy applications and drugs targeting the cancers that rely on this mechanism.
STUDIES OF NF-E4, A NOVEL FETAL/ERYTHROID SPECIFIC FACTOR INVOLVED IN FETAL GLOBIN GENE REGULATION
Funder
National Health and Medical Research Council
Funding Amount
$753,810.00
Summary
Sickle cell anemia and thalassemia are the commonest genetic disorders worldwide. Those affected suffer devastating clinical sequelae and mortality in the first twenty years of life remains high. A cure for these diseases is dependent on the replacement of the affected or absent hemoglobin protein chains with normally functioning hemoglobins. This is evident in rare patients who co-inherit a natural mutation which elevates fetal hemoglobin (HbF), as these patients have a dramatically ameliorated ....Sickle cell anemia and thalassemia are the commonest genetic disorders worldwide. Those affected suffer devastating clinical sequelae and mortality in the first twenty years of life remains high. A cure for these diseases is dependent on the replacement of the affected or absent hemoglobin protein chains with normally functioning hemoglobins. This is evident in rare patients who co-inherit a natural mutation which elevates fetal hemoglobin (HbF), as these patients have a dramatically ameliorated clinical course. Therefore, treatment strategies which could reactivate fetal globin gene expression after birth should be explored for these diseases. To achieve this goal we must further our understanding of the normal mechanisms of developmental regulation of globin gene expression. To this end we have recently identified a novel gene which is critical for fetal globin expression. The studies we propose here will further define the function of this gene and assess its potential for gene therapy for sickle cell disease and thalassemia.Read moreRead less
A genetic analysis of the role of an atypical hexokinase in gene regulation. This project addresses a question which is relevant to all living things-how do changes in the environment of a cell bring about a change in gene expression? The aim of this project is to investigate the role of hexokinases in gene regulation by studying the Aspergillus nidulans xprF gene, which encodes an an unusual hexokinase. Hexokinases are thought to be the glucose sensors in plants, animals and fungi, and play a ....A genetic analysis of the role of an atypical hexokinase in gene regulation. This project addresses a question which is relevant to all living things-how do changes in the environment of a cell bring about a change in gene expression? The aim of this project is to investigate the role of hexokinases in gene regulation by studying the Aspergillus nidulans xprF gene, which encodes an an unusual hexokinase. Hexokinases are thought to be the glucose sensors in plants, animals and fungi, and play a role in the development of diabetes in humans. In plants, sugars affect many processes including growth, flowering, photosynthesis, nitrogen metabolism, starch synthesis, pigmentation and response to pathogens.Read moreRead less
The role of neurohormones in the regulation of appetite and successful sea water transfer in farmed Atlantic salmon. Cultured Atlantic salmon spend the first part of their life in freshwater and then following a physiological adaption phase called smoltification, the fish (now termed smolts) are transferred to sea cages for growout. A proportion of smolts fail to thrive after transfer, show slow or no growth and usually die some months later. This project will investigate the role that the neuro ....The role of neurohormones in the regulation of appetite and successful sea water transfer in farmed Atlantic salmon. Cultured Atlantic salmon spend the first part of their life in freshwater and then following a physiological adaption phase called smoltification, the fish (now termed smolts) are transferred to sea cages for growout. A proportion of smolts fail to thrive after transfer, show slow or no growth and usually die some months later. This project will investigate the role that the neurohomones that control both appetite and physiological stress in fish have in stimulating the resumption of feeding after sea water transfer.The basic knowledge generated will be used directly in development of strategies for minimising smolt failure in Atlantic salmon aquaculture.Read moreRead less
The cellular basis of temperature impairment of reproductive function in Atlantic salmon. Elevated summer and autumn temperatures, either as a result of normal climate variation or global warming, inhibit reproduction in salmonid fishes by disrupting endocrine (hormonal processes). The mechanisms involved are unclear but are known to involve inhibition of ovarian estrogen and the assembly of egg-yolk proteins. This project will investigate the cellular basis of the inhibitory effect of high temp ....The cellular basis of temperature impairment of reproductive function in Atlantic salmon. Elevated summer and autumn temperatures, either as a result of normal climate variation or global warming, inhibit reproduction in salmonid fishes by disrupting endocrine (hormonal processes). The mechanisms involved are unclear but are known to involve inhibition of ovarian estrogen and the assembly of egg-yolk proteins. This project will investigate the cellular basis of the inhibitory effect of high temperature on reproduction, at the ovarian and hepatic levels. The understanding developed will be an essential component of amelioration strategies for managing the continued successful rearing of salmon and trout under warming environmental conditions.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0347223
Funder
Australian Research Council
Funding Amount
$100,000.00
Summary
Quantitative PCR facility for New England region of NSW. The project will deliver the first real-time PCR facility in the New England Region of NSW for use by University, CSIRO and Industry scientists. The facility will be based at the University of New England and be used by animal scientists, molecular biologists, parasitologists, immunologists and botanists at these institutions, in many cases in collaborative research projects. It will also support the training of seven PhD students and a po ....Quantitative PCR facility for New England region of NSW. The project will deliver the first real-time PCR facility in the New England Region of NSW for use by University, CSIRO and Industry scientists. The facility will be based at the University of New England and be used by animal scientists, molecular biologists, parasitologists, immunologists and botanists at these institutions, in many cases in collaborative research projects. It will also support the training of seven PhD students and a post-doctoral fellow. The facility will be unique to the region and will remove our current need to use facilities in Brisbane or Sydney.Read moreRead less
Regulation of the EphA3 receptor tyrosine kinase in vertebrate development. The Eph/ephrin system has a critical role in normal embryonic development. Amongst vertebrates, the EphA3 gene is one of the most highly conserved genes in this system with critical roles in development of the visual system and in other developmental processes. Understanding how this gene is regulated will help us to understand the critical role of EphA3 in the basic biology of humans and other animals. This knowledge ma ....Regulation of the EphA3 receptor tyrosine kinase in vertebrate development. The Eph/ephrin system has a critical role in normal embryonic development. Amongst vertebrates, the EphA3 gene is one of the most highly conserved genes in this system with critical roles in development of the visual system and in other developmental processes. Understanding how this gene is regulated will help us to understand the critical role of EphA3 in the basic biology of humans and other animals. This knowledge may also shed light on the basis of congenital abnormalities and other pathological processes and possibly help us to understand how to prevent or treat these conditions.Read moreRead less
The Role of C-kit and Selected TGF beta Family Members in Recruitment. The recruitment of primordial follicles into the growth phase is central to female reproductive function, however the control of this process to date, has been poorly understood due to inadequate technologies. Our team has recently developed novel recruitment models and a new and innovative method of isolating primordial follicles which will enable us to identify the role of c-kit and selected TGF beta family members in recru ....The Role of C-kit and Selected TGF beta Family Members in Recruitment. The recruitment of primordial follicles into the growth phase is central to female reproductive function, however the control of this process to date, has been poorly understood due to inadequate technologies. Our team has recently developed novel recruitment models and a new and innovative method of isolating primordial follicles which will enable us to identify the role of c-kit and selected TGF beta family members in recruitment. This work will provide cornerstone scientific knowledge about the control of female reproduction and provide the impetus for the development of more effective contraception and superovulation strategies in mammals.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775587
Funder
Australian Research Council
Funding Amount
$532,000.00
Summary
Correlating Genomics and Proteomics for Systems Biology: integrating the '-omics'. Acquisition of the infrastructure requested will maintain and extend the expertise developed by researchers in NSW and will allow retention and attraction of leading researchers who can contribute to understanding how genes and proteins interact in the development of the organism - the central focus of systems biology. The enhancement of the facility will allow a better understanding of biomolecular interactions ....Correlating Genomics and Proteomics for Systems Biology: integrating the '-omics'. Acquisition of the infrastructure requested will maintain and extend the expertise developed by researchers in NSW and will allow retention and attraction of leading researchers who can contribute to understanding how genes and proteins interact in the development of the organism - the central focus of systems biology. The enhancement of the facility will allow a better understanding of biomolecular interactions in health and disease, providing both community and national benefits. The focus of this LIEF application is to provide infrastructure platforms for the study of the systems biology of organisms and additional capacity by the facility for the expected increased demand for this technology in this new area. Read moreRead less