Why is most of the genetic variance for complex traits undetected by large powerful screens of common variants? The genomics revolution has made it possible to measure thousands of DNA variants in individuals. These variants have been associated with phenotypic outcomes in a range of species. Paradoxically, even very large studies have only accounted for a fraction of the resemblance between relatives that we know exist. Our study will test three specific hypotheses to explain this paradox. A be ....Why is most of the genetic variance for complex traits undetected by large powerful screens of common variants? The genomics revolution has made it possible to measure thousands of DNA variants in individuals. These variants have been associated with phenotypic outcomes in a range of species. Paradoxically, even very large studies have only accounted for a fraction of the resemblance between relatives that we know exist. Our study will test three specific hypotheses to explain this paradox. A better understanding about the genetic architecture for complex traits will improve the efficiency of gene mapping methods, including applications in humans for traits related to productive ageing and a healthy start to life, will lead to more efficient selection programs in agricultural populations and will inform us with respect to past evolutionary events.Read moreRead less
Identifying genes causing thermal evolution of ectotherm body size. Cold-blooded animals increase in body size as they are found in populations at greater distances from the equator. These patterns are due to populations adapting to temperature. The aim of this project is to identify the genes involved in this adaptation process. We will do this by taking advantage of a well-studied body size cline in the vinegar fly on the east coast of Australia, and by building on an international collaborati ....Identifying genes causing thermal evolution of ectotherm body size. Cold-blooded animals increase in body size as they are found in populations at greater distances from the equator. These patterns are due to populations adapting to temperature. The aim of this project is to identify the genes involved in this adaptation process. We will do this by taking advantage of a well-studied body size cline in the vinegar fly on the east coast of Australia, and by building on an international collaboration between a leading UK and two Australian research groups. In doing so we will provide an explanation at the molecular level for one of the great unresolved phenomena in biology: why do cold-blooded animals get bigger in the cold? The research also leads to the potential to manipulate body size in animals.Read moreRead less
When to Flower - analysis of a novel genetic locus (FLH) that accelerates flowering. The development of plants is largely determined by the environment. The flowering time of some plants, including many crop species, is accelerated by vernalization, a long period of low temperature. Using a combination of genetic and molecular techniques in the model plant Arabidopsis, this project will characterise a novel locus, FLH that enhances the response to vernalization. The identification of FLH will si ....When to Flower - analysis of a novel genetic locus (FLH) that accelerates flowering. The development of plants is largely determined by the environment. The flowering time of some plants, including many crop species, is accelerated by vernalization, a long period of low temperature. Using a combination of genetic and molecular techniques in the model plant Arabidopsis, this project will characterise a novel locus, FLH that enhances the response to vernalization. The identification of FLH will significantly enhance our understanding of flowering time pathways, and may lead to the generation of plant varieties designed to flower faster or slower than usual.Read moreRead less
The effect of mitochondrial and nuclear-cytoplasmic variation on longevity, metabolism and stress resistance in Drosophila. Much research points to a major role of free radical damage in aging, thus the belief that antioxidants might be beneficial in delaying aging. Free radicals are mostly formed in the subcellular organelles which consume oxygen and produce energy, and this may be the major site of age-related damage. This project seeks to understand the degree to which variation among these ....The effect of mitochondrial and nuclear-cytoplasmic variation on longevity, metabolism and stress resistance in Drosophila. Much research points to a major role of free radical damage in aging, thus the belief that antioxidants might be beneficial in delaying aging. Free radicals are mostly formed in the subcellular organelles which consume oxygen and produce energy, and this may be the major site of age-related damage. This project seeks to understand the degree to which variation among these subcellular organelles affect free radical damage and aging, using the fruitfly Drosophila melanogaster as a model organism.Read moreRead less
Estimation of non-additive genetic variance for complex traits using genome-wide single nucleotide polymorphyisms and sequence data. Finding genes for traits of importance in agriculture, ecology and human health depends on understanding the genetic basis of these traits. This project will investigate whether variation in traits in humans, cattle and wild sheep are influenced by gene-gene interactions.
The genetic architecture and evolution of quantitative traits. Most important traits are controlled by many genes and by the environment, however there is little knowledge of how many genes are involved in these complex traits and what their effects are. This project will describe the number of genes and their effects for complex traits in humans and livestock and explain how these genes evolve.
Breaking selective constraints: is Hsp90 a capacitor of evolutionary change? Gene action and expression can be modulated by genetic mechanisms. If a general mechanism controlling gene expression exists that can be easily manipulated it has the potential to allow animal and plant breeders to quickly produce and select for new characters of agricultural importance without relying on transgenics and long-term breeding programs. It would also assist in the development of tools for identifying and de ....Breaking selective constraints: is Hsp90 a capacitor of evolutionary change? Gene action and expression can be modulated by genetic mechanisms. If a general mechanism controlling gene expression exists that can be easily manipulated it has the potential to allow animal and plant breeders to quickly produce and select for new characters of agricultural importance without relying on transgenics and long-term breeding programs. It would also assist in the development of tools for identifying and detecting genes that increase susceptibility to human diseases, such as cancer, that are only expressed under certain conditions environmental. I intend to determine whether the protein Hsp90 represents a general mechanism controlling gene expression. Read moreRead less
A paradigm of genomic discovery - an investigation of the allelic architecture of height. Understanding the complexities of the human body from its DNA sequence has proven difficult. Genomic discovery is best developed using stable, easily measurable and highly heritable characteristics such as height. By taking advantage of 2 large population surveys of adult and adolescent stature we shall apply modern molecular techniques and statistical strategies to identify and characterise the exact chang ....A paradigm of genomic discovery - an investigation of the allelic architecture of height. Understanding the complexities of the human body from its DNA sequence has proven difficult. Genomic discovery is best developed using stable, easily measurable and highly heritable characteristics such as height. By taking advantage of 2 large population surveys of adult and adolescent stature we shall apply modern molecular techniques and statistical strategies to identify and characterise the exact changes in DNA that determine height. This work builds on substantial preliminary leads from unique resources and complementary expertise in the scientific specialties. The results from this work will inform other genomic research and provide information about growth and bone biology.Read moreRead less
Nanoelectromechanical Mass Spectrometry with Molecular Imaging. This project aims to develop new technology to enable simultaneous measurement of the mass and conformation of single molecules. Mass spectrometry and high-resolution microscopy are independent analytical tools used widely to characterise the chemical and physical properties of molecules. This project aims to develop new technology based on advanced nanoelectromechanical systems that combines the capabilities of these complementary ....Nanoelectromechanical Mass Spectrometry with Molecular Imaging. This project aims to develop new technology to enable simultaneous measurement of the mass and conformation of single molecules. Mass spectrometry and high-resolution microscopy are independent analytical tools used widely to characterise the chemical and physical properties of molecules. This project aims to develop new technology based on advanced nanoelectromechanical systems that combines the capabilities of these complementary instruments. This would enable synchronous measurement of molecular mass and conformation with nanometre resolution. In contrast to current mass spectrometry, this technology could be operated in fluid and detect neutral species. This significant change in capability could be applied to advance biological and medical research.Read moreRead less
Statistical Methods for Discovering Ribonucleic acids (RNAs) contributing to human diseases and phenotypes. Identifying the causative genetic factors involved in quantitative phenotypes and diseases is a major goal of biology in the 21st century and beyond. A crucial step towards this goal is identifying and classifying the functional non-protein-coding Ribonucleic acids (RNAs) encoded in the human genome. This project will make major contributions to international efforts in this area by identi ....Statistical Methods for Discovering Ribonucleic acids (RNAs) contributing to human diseases and phenotypes. Identifying the causative genetic factors involved in quantitative phenotypes and diseases is a major goal of biology in the 21st century and beyond. A crucial step towards this goal is identifying and classifying the functional non-protein-coding Ribonucleic acids (RNAs) encoded in the human genome. This project will make major contributions to international efforts in this area by identifying RNA molecules that contribute to quantitative phenotypes including susceptibility to disease. As such, it will directly benefit fundamental science via the discovery and classification of new molecules. Indirectly, it will lead to breakthroughs in biology, and consequently to major medical and pharmaceutical advances in the diagnosis and treatment of genetic disease.Read moreRead less