Regulation Of Pre-mRNA And MRNA Processing By The Neuron-specific Hu RNA-binding Proteins
Funder
National Health and Medical Research Council
Funding Amount
$477,750.00
Summary
The precise control of protein expression is absolutely critical in biology, and the key decisions about which genes are turned on or off at any one moment control the proper growth and maturation of an organism during development, and are responsible for the organism's homeostasis and proper response to environmental changes as an adult. Many gene expression programs are highly complex and controlled by regulating the activation of individual genes as they are copied from DNA to RNA. However, t ....The precise control of protein expression is absolutely critical in biology, and the key decisions about which genes are turned on or off at any one moment control the proper growth and maturation of an organism during development, and are responsible for the organism's homeostasis and proper response to environmental changes as an adult. Many gene expression programs are highly complex and controlled by regulating the activation of individual genes as they are copied from DNA to RNA. However, this activation is just the start of the process to produce an active protein. In higher organisms, these RNA copies almost always contain interruptions called introns, which must be excised from the RNA. Also, protein factors bound to specific RNAs can dictate whether the RNA is used to make protein or not, and these factors can also affect the localisation of the RNA to a specific sub-cellular destination, giving rise to highly localised protein expression. Evidence suggests that neurons are a cell type that rely heavily on mechanisms of RNA regulation. During development neurons become highly polarised, acquiring an axon which can elongate and find distant synaptic targets. While much is known about how axon growth cones respond to various guidance cues, the mechanisms by which the axon is able to translate this guidance cue information into structural changes which allow the growth cone to expand or collapse is largely unexplored. Recent evidence suggests that accurate growth cone guidance is absolutely dependent upon local protein synthesis. The functional corollary of this finding is that axon guidance requires RNA localisation and control of protein synthesis of RNAs in the growth cone. This phenomenon of spatial gene regulation within an individual cell is a central research interest for understanding how the brain functions.Read moreRead less
The regulation of skeletal muscle mass. This project aims to delineate a pathway involved in regulating skeletal muscle mass, and examine whether disrupting mitochondrial phospholipid synthesis affects mitochondrial structure and function, causing muscle wasting. Defining a new atrophy pathway will advance understanding of the mechanisms that control muscle mass. This project could have important economic and quality of life benefits, especially for agriculture, where achieving optimal muscle ma ....The regulation of skeletal muscle mass. This project aims to delineate a pathway involved in regulating skeletal muscle mass, and examine whether disrupting mitochondrial phospholipid synthesis affects mitochondrial structure and function, causing muscle wasting. Defining a new atrophy pathway will advance understanding of the mechanisms that control muscle mass. This project could have important economic and quality of life benefits, especially for agriculture, where achieving optimal muscle mass ensures international competitiveness, productivity and economic growth, and successful ageing, where maintaining muscle mass is essential.Read moreRead less
Investigation of the biochemical and physiological functions of the negative regulator of cytokine signalling SOCS-2. Cytokines exert their effects by binding and signalling through specific cell surface receptors to elicit their biological action, and if left unchecked, this signalling can cause significant tissue damage and toxicity. Our aim is to characterise a novel regulator of cytokine signalling, SOCS-2. SOCS-2 is strongly implicated in the regulation of post-natal growth as SOCS-2 defici ....Investigation of the biochemical and physiological functions of the negative regulator of cytokine signalling SOCS-2. Cytokines exert their effects by binding and signalling through specific cell surface receptors to elicit their biological action, and if left unchecked, this signalling can cause significant tissue damage and toxicity. Our aim is to characterise a novel regulator of cytokine signalling, SOCS-2. SOCS-2 is strongly implicated in the regulation of post-natal growth as SOCS-2 deficient animals are 40 percent larger than normal. Consequently, we wish to determine how SOCS-2 acts to limit the size of an animal and whether this involves regulation of growth hormone action.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120101242
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Regulation of germ cell number and quality by Fizzy-related protein. Females have a limited supply of eggs in their ovaries and it appears that the Fizzy-related gene (FZR1) is important in making sure this full complement is gained. By using novel mouse knockouts of the FZR1 gene, the project will determine how this protein functions at the earliest stages of egg development.
Molecular control of embryonic diapause. Many species can halt growth of the early embryo (diapause). This project will use novel animal models and new proteomics techniques to clarify what signals from the uterus control diapause of the embryo. This may uncover new mechanisms for cell regulation that will be relevant to the biology of stem cells, cancer and reproductive technologies.
Revealing the mechanobiology of neural tube formation. This project aims to understand the formation of the neural tube; a fundamental tissue structure that generates the brain and the spinal cord. Using interdisciplinary approaches and exploiting recent advances in transgenic and imaging technologies, we expect to reveal the complex interplay between cells and their environment that generates mechanical forces to direct neural tissue formation. Outcomes include knowledge of previously intractab ....Revealing the mechanobiology of neural tube formation. This project aims to understand the formation of the neural tube; a fundamental tissue structure that generates the brain and the spinal cord. Using interdisciplinary approaches and exploiting recent advances in transgenic and imaging technologies, we expect to reveal the complex interplay between cells and their environment that generates mechanical forces to direct neural tissue formation. Outcomes include knowledge of previously intractable developmental processes, training of future scientists and development of international collaborations. This should provide enhanced imaging capacity, a higher quality scientific workforce and position Australia at the forefront of cell and developmental biology.Read moreRead less
Reverse chemical proteomics: harnessing yeast display for drug discovery. This project aims to develop a technique that can rapidly identify the cellular protein targets of biologically active natural products. This project expects to provide fundamental biological and chemical insights into Australia's unique biodiversity that will facilitate the development of new therapeutic agents and agrochemicals based on leads provided by Nature. Expected outcomes of this project include an optimised and ....Reverse chemical proteomics: harnessing yeast display for drug discovery. This project aims to develop a technique that can rapidly identify the cellular protein targets of biologically active natural products. This project expects to provide fundamental biological and chemical insights into Australia's unique biodiversity that will facilitate the development of new therapeutic agents and agrochemicals based on leads provided by Nature. Expected outcomes of this project include an optimised and validated platform technology for accelerating drug discovery and development. This should substantially reduce the costs associated with fighting human and animal diseases, leading to improved health, productivity and quality of life.Read moreRead less
Engineering electrochemical protein biosensors. This project plans to develop novel, sensitive, inexpensive and flexible electric biosensors to monitor potentially any molecule. It plans to use synthetic biology principles to develop a new class of artificial protein receptors that generate electric current upon encountering a molecular target. Using expertise in in vitro protein synthesis, the project plans to integrate biosensor design and electrode prototyping to achieve rapid development of ....Engineering electrochemical protein biosensors. This project plans to develop novel, sensitive, inexpensive and flexible electric biosensors to monitor potentially any molecule. It plans to use synthetic biology principles to develop a new class of artificial protein receptors that generate electric current upon encountering a molecular target. Using expertise in in vitro protein synthesis, the project plans to integrate biosensor design and electrode prototyping to achieve rapid development of low-cost broadly applicable sensory electrodes. To increase the sensitivity of the resulting sensing systems, the electrochemical receptors will be integrated with signal amplification cascades based on artificial autoinhibited proteases. The project aims to address the need for new technologies that enable collection of biological information outside of the laboratory environment.Read moreRead less