Genetic variation of single cell transcriptional heterogeneity in HiPSCs. This project aims to investigate whether induced pluripotent stem cells (iPSC) can be used to study the functions of genetic variants associated with human phenotypes and cell fate decisions. The project will utilise technology to produce single cell RNA sequence data for 100,000s of cells. By sequencing individual cells, the genetic control of cellular heterogeneity both within and between cells can be identified, and in ....Genetic variation of single cell transcriptional heterogeneity in HiPSCs. This project aims to investigate whether induced pluripotent stem cells (iPSC) can be used to study the functions of genetic variants associated with human phenotypes and cell fate decisions. The project will utilise technology to produce single cell RNA sequence data for 100,000s of cells. By sequencing individual cells, the genetic control of cellular heterogeneity both within and between cells can be identified, and in doing so, will provide significant benefit by revealing the potential for iPSC to be used for functional translation of human genomics.Read moreRead less
Preparing Australia For Genomic Medicine: A Proposal By The Australian Genomics Health Alliance
Funder
National Health and Medical Research Council
Funding Amount
$25,000,000.00
Summary
The sequencing of the human genome brings the possibility of more accurate identification of the underlying basis of many diseases. This technology has moved so rapidly, however, that clinical access has been limited. In this application, a national alliance of clinicians, researchers, health economists and policymakers will evaluate the case for clinical genomics across inherited disease and cancer, determine how best to deliver this to the patient and train a capable workforce.
Sequencing and assembling microbial community metagenomes in real-time. This project aims to assemble metagenomes directly from environmental samples using nanopore sequencing. Short-read approaches to metagenomics cannot assemble mixed genomes from an environmental sample, so focus on describing which species and genes are present. Long-read nanopore sequencing enables the assembly of full genomes of multiple species in a sample. Assembling complete genomes in important resources such as water ....Sequencing and assembling microbial community metagenomes in real-time. This project aims to assemble metagenomes directly from environmental samples using nanopore sequencing. Short-read approaches to metagenomics cannot assemble mixed genomes from an environmental sample, so focus on describing which species and genes are present. Long-read nanopore sequencing enables the assembly of full genomes of multiple species in a sample. Assembling complete genomes in important resources such as water and soil should lead to deeper understanding of the dynamics, variation and transfer of genetic material within these resources’ microbial communities, strategies to manage microbial diversity, and improved productivity and long-term sustainability for these resources.Read moreRead less
Pathogenesis Of Persistent Human Virus Infections Of Global Significance
Funder
National Health and Medical Research Council
Funding Amount
$6,571,328.00
Summary
The study will investigate why humans cannot eradicate particular viruses (HIV-AIDS, cytomegalovirus and herpes simplex virus), the long term effects of these viruses and ways to improve control. Current treatments can only partly suppress the levels of these viruses, because they persist in certain parts of the body called reservoirs, only to resurge later causing disease. Thus, the overall aim of the research program is to discover the mechanisms by which these viruses are able to successfully ....The study will investigate why humans cannot eradicate particular viruses (HIV-AIDS, cytomegalovirus and herpes simplex virus), the long term effects of these viruses and ways to improve control. Current treatments can only partly suppress the levels of these viruses, because they persist in certain parts of the body called reservoirs, only to resurge later causing disease. Thus, the overall aim of the research program is to discover the mechanisms by which these viruses are able to successfully persist within reservoirs in the human body. The research program brings together a group of 6 leading scientists and clinicians located at 3 sites in 2 Australian cities. The team is comprised of experts in the study of HIV-AIDS, cytomegalovirus and herpes simplex virus who will combine their knowledge and expertise to speed up the process of research on these viruses that are of major health importance. Studies will also utilise a number of cutting edge technologies that now make it possible to much more rapidly and precisely determine how viruses cause disease. Advances in our understanding of how viruses persist may form the basis for treatments aimed at controlling persistent infections and the serious diseases caused by these viruses.Read moreRead less
Diet influences the selective advantage of mitochondrial DNA mutations. This project aims to examine critical mechanisms that affect mitochondrial DNA variation within species. It aims to test the hypothesis that mitochondrial DNA haplotypes have the potential to be under nutritionally induced balancing selection as a consequence of cellular signalling and/or Adenosine triphosphate (ATP) production by mitochondria. Diet can vary both seasonally and geographically and is a key environmental param ....Diet influences the selective advantage of mitochondrial DNA mutations. This project aims to examine critical mechanisms that affect mitochondrial DNA variation within species. It aims to test the hypothesis that mitochondrial DNA haplotypes have the potential to be under nutritionally induced balancing selection as a consequence of cellular signalling and/or Adenosine triphosphate (ATP) production by mitochondria. Diet can vary both seasonally and geographically and is a key environmental parameter that influences the ability of a species to colonise new habitats. The project plans to characterise the functional links between specific mitochondrial DNA haplotypes, mitochondrial functions and organismal traits. The expected outcome is a more precise grasp of the processes influencing genetic variation within and among species, which would inform current issues in ecology and genetics.Read moreRead less
Next generation high throughput lipidomics using adaptive modelling. This project aims to develop a unique high-throughput method to capture the lipidomic profile of human plasma suitable for large human population screening. Lipids are fundamental to every biological system, but our understanding of their regulation in humans have been largely superficial. By incorporating a new lipidomics approach, with genomic data, this project aims to expand our understanding of human biology by identifying ....Next generation high throughput lipidomics using adaptive modelling. This project aims to develop a unique high-throughput method to capture the lipidomic profile of human plasma suitable for large human population screening. Lipids are fundamental to every biological system, but our understanding of their regulation in humans have been largely superficial. By incorporating a new lipidomics approach, with genomic data, this project aims to expand our understanding of human biology by identifying regulators of lipid metabolism. The large diversity in humans necessitate sufficient sample sizes to identify true genetic regulators, but to date techniques capturing phenotypic data (lipids) have been largely limited. It is anticipated that this study will identify new regulators of lipid metabolism in humans.Read moreRead less
How to build the head: A molecular mechanistic insight. This project aims to gain an insight into the functional output of the gene regulatory network and the molecular determinants that are critical for the formation of the head. Genome-wide sequencing technologies are employed to identify the ensemble of genes that are regulated by Lhx1. By a combination of bioinformatics analysis and a system biology approach, the project aims to build a model of the network of the interacting genes for head ....How to build the head: A molecular mechanistic insight. This project aims to gain an insight into the functional output of the gene regulatory network and the molecular determinants that are critical for the formation of the head. Genome-wide sequencing technologies are employed to identify the ensemble of genes that are regulated by Lhx1. By a combination of bioinformatics analysis and a system biology approach, the project aims to build a model of the network of the interacting genes for head development, and to characterise the function of selected components of this network to refine its architecture and define the dynamics of the network. The knowledge may improve our understanding of the molecular mechanism underpinning the naturally-occurring variation in the forms of major body parts, and of how genes and signals work cooperatively to build an embryo.Read moreRead less
Empirical and computational solutions for multi-omics single-cell assays. Emerging single-cell sequencing technologies are transforming molecular cell biology, but identifying novel cell types and their functions requires the integration of highly heterogeneous data. The development of computational methods able to extract biologically relevant results is hindered by the lack of high-quality datasets. This project aims to develop novel sequencing methodologies and generate data to drive our dime ....Empirical and computational solutions for multi-omics single-cell assays. Emerging single-cell sequencing technologies are transforming molecular cell biology, but identifying novel cell types and their functions requires the integration of highly heterogeneous data. The development of computational methods able to extract biologically relevant results is hindered by the lack of high-quality datasets. This project aims to develop novel sequencing methodologies and generate data to drive our dimension reduction multivariate method developments for data integration. By combining in silico and in vivo approaches, the project is anticipated to benefit scientists willing to work in cutting-edge single-cell research by providing useful protocols and tools to generate novel insights in cell biology. Read moreRead less
Searching for near-exact protein models. This project aims to develop novel and efficient heuristic-based algorithms leading to near accurate protein tertiary structure models. Knowledge about protein structures is fundamental to our understanding of living systems. The progress on experimental determination of these structures has been extremely limited and remains an open challenge in molecular biology. Computational prediction of protein structures from sequences is emerging as a promising ap ....Searching for near-exact protein models. This project aims to develop novel and efficient heuristic-based algorithms leading to near accurate protein tertiary structure models. Knowledge about protein structures is fundamental to our understanding of living systems. The progress on experimental determination of these structures has been extremely limited and remains an open challenge in molecular biology. Computational prediction of protein structures from sequences is emerging as a promising approach, but its accuracy is far from satisfactory. The software systems developed in this project will be used in structural identification of target proteins in drug design. This will make drug design process more efficient, saving time and cost, potentially saving lives.Read moreRead less
Transcription factors find their targets by reading the epigenetic code. This project aims to elucidate how transcription factors, proteins that regulate gene expression, find their target genes. The hypothesis is that non-DNA binding domains play an essential role in this process. This project expects to transform our understanding of transcription factor families, and how factors in families with the same DNA-binding domain manage to regulate different genes. Expected outcomes of this project ....Transcription factors find their targets by reading the epigenetic code. This project aims to elucidate how transcription factors, proteins that regulate gene expression, find their target genes. The hypothesis is that non-DNA binding domains play an essential role in this process. This project expects to transform our understanding of transcription factor families, and how factors in families with the same DNA-binding domain manage to regulate different genes. Expected outcomes of this project include revealing how accessory proteins help transcription factors identify their targets in the genome by reading epigenetic marks. This should provide significant benefits including improved design of artificial transcription factors to up- or down-regulate specific genes in research and agriculture.Read moreRead less