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
Understanding How Azithromycin Prevents Exacerbations In Severe Asthma
Funder
National Health and Medical Research Council
Funding Amount
$697,273.00
Summary
In some people with severe asthma, conventional inhaler treatments are not able to control the disease so there is a need for new treatment options. We have recently completed a large clinical trial which showed that very low doses of a common antibiotic help prevent asthma attacks in this situation. However, not much is known about how the antibiotic is working. This study will help us understand how the antibiotic is working and which people respond best.
Discovery Early Career Researcher Award - Grant ID: DE150101117
Funder
Australian Research Council
Funding Amount
$327,000.00
Summary
The functional impact of new genes acquired through retrotransposition. Novel copies of genes often arise through retrotransposition of processed messenger RNAs. Many thousands of gene copies have arisen over evolutionary time and some of these have retained functionality while diverging from the parental gene leading to new paralogs under different regulatory regimes. Through analysis of whole-genome sequence data, we are now able to identify very recent gene copies that are not present in the ....The functional impact of new genes acquired through retrotransposition. Novel copies of genes often arise through retrotransposition of processed messenger RNAs. Many thousands of gene copies have arisen over evolutionary time and some of these have retained functionality while diverging from the parental gene leading to new paralogs under different regulatory regimes. Through analysis of whole-genome sequence data, we are now able to identify very recent gene copies that are not present in the reference genomes for various species, giving us the opportunity to explore the effects of new copies on the regulation of the original gene and the surrounding genomic environment into which the new copy is inserted. This project aims to address these important open questions through computational and biochemical approaches.Read moreRead less
Reconstructing proteins to explain and engineer biological diversity. The aim of this project is to develop computational methods to construct entirely new proteins. Computational reconstruction of enzymes that have been extinct for over 400 million years has revealed remarkable opportunities for biotechnological innovation. The intended outcomes are to develop bioinformatics methods to broaden the scope of ancestral protein reconstruction to include protein super-families, to establish what spe ....Reconstructing proteins to explain and engineer biological diversity. The aim of this project is to develop computational methods to construct entirely new proteins. Computational reconstruction of enzymes that have been extinct for over 400 million years has revealed remarkable opportunities for biotechnological innovation. The intended outcomes are to develop bioinformatics methods to broaden the scope of ancestral protein reconstruction to include protein super-families, to establish what specific changes led to the evolutionary success of a protein, and to re-run evolution to generate proteins that perform in conditions suitable for industrial and agricultural applications, in particular the production of hydroxylated fatty acids for bioplastics. By examining proteins from many life forms, the project plans to develop a novel bioinformatics strategy to understand their evolution and engineer new proteins for use in production of chemical commodities.Read moreRead less
KLK4 Is A Master Regulator Of Tumour Microenvironment Remodelling In Prostate Cancer And Bone Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$596,305.00
Summary
The current biomarker for prostate cancer, PSA, belongs to a large family of related proteins called KLK enzymes. We have evidence that one of these enzymes, KLK4, regulates many different pathways involved in tumour spreading especially to bones. This project will determine the specific components involved with a view to finding better biomarkers of tumour spread and bone metastasis and designing better treatments for these aspects of the disease.
Discovery Early Career Researcher Award - Grant ID: DE190101078
Funder
Australian Research Council
Funding Amount
$374,433.00
Summary
Functional role of a novel DNA modification in the adult brain. This project aims to understand how neuronal DNA is modified upon learning and how this impacts memory formation. The project will investigate the combination of different genome-wide sequencing approaches and molecular and cell biological assays to provide new insight into the functional role of a novel DNA modification, N6-methyl-2'-deoxyadenosine in the adult brain. This projects expects to have a major impact on many fields, inc ....Functional role of a novel DNA modification in the adult brain. This project aims to understand how neuronal DNA is modified upon learning and how this impacts memory formation. The project will investigate the combination of different genome-wide sequencing approaches and molecular and cell biological assays to provide new insight into the functional role of a novel DNA modification, N6-methyl-2'-deoxyadenosine in the adult brain. This projects expects to have a major impact on many fields, including neuroscience, evolutionary biology, and genetics, by helping to shape a new way of thinking about gene-environment interactionsRead moreRead less
Discovery Early Career Researcher Award - Grant ID: DE190100116
Funder
Australian Research Council
Funding Amount
$415,737.00
Summary
Cell types and cell states revealed by single-cell regulatory networks. This project aims to use single-cell gene regulation networks to predict cell types. Computational approaches are needed to recapitulate how the over 37 trillion cells program the shared genome sequence in a human body to create astoundingly diverse forms and functions. This project integrates millions of high-resolution single-cell gene expression profiles with large-scale population regulatory data to systematically recons ....Cell types and cell states revealed by single-cell regulatory networks. This project aims to use single-cell gene regulation networks to predict cell types. Computational approaches are needed to recapitulate how the over 37 trillion cells program the shared genome sequence in a human body to create astoundingly diverse forms and functions. This project integrates millions of high-resolution single-cell gene expression profiles with large-scale population regulatory data to systematically reconstruct gene regulatory networks. These networks are the molecular basis for understanding human cells. This projects outcomes intend to include the first reference single-cell regulatory database and novel methods and software to predict individual cells. This project will contribute to advancing Australia's capabilities in single-cell, precision medicine, and big biological data analysis leading to significant scientific, societal and commercial benefits.Read moreRead less
Computational systems biology: understanding mammalian cell fates using genome-scale network models. Mutations can disrupt the cellular networks that control normal development, causing cells to develop abnormally including in ways that lead to cancer. The project will analyse genome sequences from more than 700 pancreatic cancers and matched controls to precisely map the causative trail from mutations to disrupted networks to altered cell development.
Novel antimicrobial target discovery by an integrated approach. The project aims to uncover the molecular targets of BDM-I, a novel antimicrobial candidate discovered by the start-up Australian company BioDiem Ltd. BDM-I is active against many drug resistant bacterial and fungal microorganisms and it is currently in pre-clinical development. However, the lack of resistant phenotypes makes it difficult to identify BDM-I’s mechanism of action. The project plans to use an integrated approach that c ....Novel antimicrobial target discovery by an integrated approach. The project aims to uncover the molecular targets of BDM-I, a novel antimicrobial candidate discovered by the start-up Australian company BioDiem Ltd. BDM-I is active against many drug resistant bacterial and fungal microorganisms and it is currently in pre-clinical development. However, the lack of resistant phenotypes makes it difficult to identify BDM-I’s mechanism of action. The project plans to use an integrated approach that combines a novel technique of in silico screening with experimental validation. Project outcomes are anticipated to include the first computational method to integrate target and ligand similarity for proteome-scale target and off-target discovery, which will advance the global fight against drug-resistant microorganisms.Read moreRead less