microRNAs: discovery and analysis in mouse development. MicroRNAs (miRNAs) are a new class of regulatory molecule, recently found to be abundant and strongly conserved in several eukaryotic species, encoded by genes that are transcribed into short stem-loop structures and then processed into ~22nt single-stranded RNAs by the RNAi pathway. We have cloned novel miRNAs, and obtained the first evidence for regulation of a miRNA in a mammal. We propose to continue cloning novel miRNAs by the tried m ....microRNAs: discovery and analysis in mouse development. MicroRNAs (miRNAs) are a new class of regulatory molecule, recently found to be abundant and strongly conserved in several eukaryotic species, encoded by genes that are transcribed into short stem-loop structures and then processed into ~22nt single-stranded RNAs by the RNAi pathway. We have cloned novel miRNAs, and obtained the first evidence for regulation of a miRNA in a mammal. We propose to continue cloning novel miRNAs by the tried method, and to explore bioinformatics-based methods of identification. We will also study the expression of miRNAs in mouse embryos at successive stages, and develop a microarray assay for miRNA expression.Read moreRead less
A role for Cited2, Transforming Growth Factor-beta and matrix metaloproteinases in trophoblast invasion and placenta formation. The placenta is essential for the growth and development of the fetus, and if it fails to form correctly during pregnancy, it can have dramatic effects that can result death in utero, or adult onset diseases. Our research aims to understand how one protein functions in placenta formation. We will also investigate how this protein works at the molecular level in a proces ....A role for Cited2, Transforming Growth Factor-beta and matrix metaloproteinases in trophoblast invasion and placenta formation. The placenta is essential for the growth and development of the fetus, and if it fails to form correctly during pregnancy, it can have dramatic effects that can result death in utero, or adult onset diseases. Our research aims to understand how one protein functions in placenta formation. We will also investigate how this protein works at the molecular level in a process that enables single cells to respond to molecules sent from a distance by other cells (TGF-beta signalling). This process is also very important for a host of other biological processes relevant to human health, including cancer.Read moreRead less
Specification and evolution of vertebrate appendicular muscle. Previously we have determined that two different developmental mechanisms are utilised to make the muscles present within the fins and limbs of distinct vertebrate species. This proposal is concerned with determining the morphogenetic, evolutionary and molecular basis for these two different developmental modes. To do this we will to extend our observations more widely to examine muscle formation in both the paired fins in a phyloge ....Specification and evolution of vertebrate appendicular muscle. Previously we have determined that two different developmental mechanisms are utilised to make the muscles present within the fins and limbs of distinct vertebrate species. This proposal is concerned with determining the morphogenetic, evolutionary and molecular basis for these two different developmental modes. To do this we will to extend our observations more widely to examine muscle formation in both the paired fins in a phylogenetically diverse context. We further hope to determine the underlying genetic basis for these different morphologies by developing techniques to examine their formation in a number of embryonic contexts.Read moreRead less
Endocardial sprouting and mechano-signalling in heart trabeculation. This project aims to understand how the ventricles, the pumping chambers of the mammalian heart, form during embryonic life. Critical is the elaboration of trabeculae, myocardial projections that form a sponge-like layer on the inner surface of the chamber wall and which play vital roles in contraction, oxygen and nutrient exchange, conduction and septation. The project expects to develop a deeper understanding of trabeculation ....Endocardial sprouting and mechano-signalling in heart trabeculation. This project aims to understand how the ventricles, the pumping chambers of the mammalian heart, form during embryonic life. Critical is the elaboration of trabeculae, myocardial projections that form a sponge-like layer on the inner surface of the chamber wall and which play vital roles in contraction, oxygen and nutrient exchange, conduction and septation. The project expects to develop a deeper understanding of trabeculation using high resolution, single cell methodologies, and to investigate how bio-mechanical forces from contraction or blood flow influence chambers formation.Read moreRead less
Functional analysis of nucleic acid binding protein that is essential for mammalian development. The complex pathway by which the information contained in our genes is used by the body is far from understood. The project will explore an important protein component of this pathway, that is essential for normal embryonic development. The aim of this project is to understand how this protein regulates human development.
Exploration of a mechanistic link between eukaryotic transcription and translation. Gene transcription is functionally coupled to other aspects of eukaryotic mRNA metabolism, emphasizing a need for integrated approaches to analyse the gene expression pathway. We have shown in previous work that yeast cells, when responding to external stimuli, show a tight correlation between changes in the transcriptome composition and homodirectional alterations in the translation state of mRNAs. This phenomen ....Exploration of a mechanistic link between eukaryotic transcription and translation. Gene transcription is functionally coupled to other aspects of eukaryotic mRNA metabolism, emphasizing a need for integrated approaches to analyse the gene expression pathway. We have shown in previous work that yeast cells, when responding to external stimuli, show a tight correlation between changes in the transcriptome composition and homodirectional alterations in the translation state of mRNAs. This phenomenon of ?potentiation? may serve to amplify signal-induced changes in the transcriptome at the translational level. This project will begin to unravel the molecular mechanisms underlying potentiation using experiments designed to distinguish between transcription- and translation-driven mechanisms.Read moreRead less
Genetic and molecular basis of appendicular muscle formation. Fin and limb muscles are generated in the embryo by a series of cell movements and gene regulatory events that are distinct to those that regulate the formation of the rest of the muscles of the body. This project aims to use the genetic advantages of zebrafish to determine how genes regulate fin and consequently limb muscle formation.
The importance of DNA methylation in response to environmental changes. This project aims to investigate the importance of DNA methylation, a process whereby gene expression can be altered without changes in the DNA code, in regulating our responses to environmental challenges. It plans to do so using well-validated models of adult exposure to high fat diet or psychological stress in mice and tissue-specific (liver and brain) deletion of the major methylation enzymes. It aims to compare function ....The importance of DNA methylation in response to environmental changes. This project aims to investigate the importance of DNA methylation, a process whereby gene expression can be altered without changes in the DNA code, in regulating our responses to environmental challenges. It plans to do so using well-validated models of adult exposure to high fat diet or psychological stress in mice and tissue-specific (liver and brain) deletion of the major methylation enzymes. It aims to compare functional, gene expression and methylation status after such challenges in intact and methylase deleted animals to determine how vital this process really is. This work has major implications for our understanding of epigenetics, and the ways in which genes interact with the environment especially in times of change.Read moreRead less
Investigating a new way in which diet impacts animal biology. This project aims to investigate the importance of a new way in which diet can alter animal biology. High fat or high sugar diets increase the binding of products of metabolism to chromosomes, which can completely alter the way that DNA is packaged and read. This project will use cell culture, rodent and fly models to identify the regions of the genome that are most affected by the new process. The project will also determine whether ....Investigating a new way in which diet impacts animal biology. This project aims to investigate the importance of a new way in which diet can alter animal biology. High fat or high sugar diets increase the binding of products of metabolism to chromosomes, which can completely alter the way that DNA is packaged and read. This project will use cell culture, rodent and fly models to identify the regions of the genome that are most affected by the new process. The project will also determine whether the cell is harmed, or in fact harnesses the process to control development or metabolism. This project has implications for our understanding of the ways in which genes interact with the environment especially in times of change.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE130100894
Funder
Australian Research Council
Funding Amount
$361,140.00
Summary
Nanolamps: unlocking targeted gene silencing in deep tissue with nanoparticle-based light sources. In order to better understand the function of genes, this project will develop a new method of tightly targeted gene silencing deep inside of the body by nanoscale light sources. This will shed new light on the nervous system and, in the first instance, help to elucidate the role of the PACAP neurons in blood pressure regulation.