Discovery Early Career Researcher Award - Grant ID: DE200101323
Funder
Australian Research Council
Funding Amount
$427,098.00
Summary
Structure guided mapping of protein interactions and their perturbation. Protein interactions are central to most biological processes, and significant effort has been devoted to trying to unravel these complicated networks. This project aims to develop new approaches to better understand these interactions, and the consequences of their perturbation. The main expected contributions will be: (i) methods to identify likely protein interaction sites using population conservation; (ii) computationa ....Structure guided mapping of protein interactions and their perturbation. Protein interactions are central to most biological processes, and significant effort has been devoted to trying to unravel these complicated networks. This project aims to develop new approaches to better understand these interactions, and the consequences of their perturbation. The main expected contributions will be: (i) methods to identify likely protein interaction sites using population conservation; (ii) computational approaches to assess the effects of any type of mutation on the interaction; and (iii) an understanding of how disruption of a specific interaction can affect the complicated biological network within a cell. 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
Evolution and functional impact of gene silencing by hairpin derived RNAs. This project aims to study RNA-mediated gene silencing in genome evolution. RNA interference (RNAi) has been widely used as an experimental tool since its Nobel Prize-winning discovery in 1998, but little is known about endogenous RNAi or its evolution. This project uses bioinformatics, high-throughput sequencing and molecular approaches to study hpRNAs, a class of small interfering RNAs, their adaptive evolution across f ....Evolution and functional impact of gene silencing by hairpin derived RNAs. This project aims to study RNA-mediated gene silencing in genome evolution. RNA interference (RNAi) has been widely used as an experimental tool since its Nobel Prize-winning discovery in 1998, but little is known about endogenous RNAi or its evolution. This project uses bioinformatics, high-throughput sequencing and molecular approaches to study hpRNAs, a class of small interfering RNAs, their adaptive evolution across fly species and vertebrates, and their functional effect on testis morphogenesis and distortion of female/male sex-ratio. The project also studies splicing-dependent small RNAs and miRNA-target interaction. This research could have applications from animal development to human pathology.Read moreRead less
Large-scale Cancer Proteomic Analyses For Improved Prediction Of Drug Response, Patient Prognosis And Clinical Outcome
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Proteomics is the study of all of the proteins encoded by a genome. In this project, I will use a new database of proteomic and clinical data from up to 70,000 cancer samples, and create an approach to correlate proteomic features with drug response, patient prognosis and clinical outcome. The aim of this research will be to use proteomics to better guide treatment decisions, with the potential to significantly improve the health of people with cancer, both in Australia and globally.
Improving Bioinformatic Methods For Studying Gene Regulation In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$463,652.00
Summary
New methods for analysing genome-wide data will be developed to ease the data analysis bottleneck that currently exists in medical research. Modelling variation in gene expression from single cells, in screens designed to uncover gene function and assays that measure the factors that turn genes on or off will be the focus. Free software will be developed and made available to researchers worldwide to help them interpret the large and complex data sets that are now routine in genomic medicine.
The systems biology of stem cells. Using new bioinformatic methods, this project aims to identify new classifiers of different stem cell populations, develop statistical models that address population heterogeneity and provide molecular predictors of the differentiation potential of stem cells. Understanding, predicting and directing the processes of differentiation are major goals in the disciplines of stem cell biology, developmental biology, tissue engineering and regenerative medicine. Molec ....The systems biology of stem cells. Using new bioinformatic methods, this project aims to identify new classifiers of different stem cell populations, develop statistical models that address population heterogeneity and provide molecular predictors of the differentiation potential of stem cells. Understanding, predicting and directing the processes of differentiation are major goals in the disciplines of stem cell biology, developmental biology, tissue engineering and regenerative medicine. Molecular atlas projects have successfully revealed rules of genome output and regulation, by mining patterns that are evident across multiple cell types and datasets. By applying this philosophy to relevant, well-curated stem cell experiments, this project aims to create new methods for the integration and interrogation of smaller individual datasets. These methods should have broad utility and enable new avenues in tissue engineering.Read moreRead less
Exploring novel coding genomic features through integrative proteogenomics. Knowledge of the full extent to which the human genome is made into proteins is of fundamental importance in the study of health and disease. New technological advances are now enabling functional studies of genomes with increasing detail. This project aims to develop and apply cutting edge bioinformatics methods to perform an integrative and comprehensive exploration of the extent to which the genes of a human cell line ....Exploring novel coding genomic features through integrative proteogenomics. Knowledge of the full extent to which the human genome is made into proteins is of fundamental importance in the study of health and disease. New technological advances are now enabling functional studies of genomes with increasing detail. This project aims to develop and apply cutting edge bioinformatics methods to perform an integrative and comprehensive exploration of the extent to which the genes of a human cell line are made into proteins. The project will improve our understanding of the human genome and deliver cutting edge methodology applicable for genome annotation in all living organisms.Read moreRead less
High-throughput genetic assays are commonly used to study the molecular basis of disease and such technology requires sophisticated data analysis methods that account for significant biological and experimental complexity. Specialized methods will be developed in free public software that will greatly benefit future genetic profiling studies.
Discovering The Genetic Causes Of Congenital Heart Disease Using Systems Biology
Funder
National Health and Medical Research Council
Funding Amount
$419,180.00
Summary
Congenital heart disease (CHD) affects one in one hundred live-born babies, representing a significant health burden in Australia and worldwide. My research team is using state-of-the-art DNA sequencing technology to sequence the entire genome of hundreds of patients with CHD and their family members. My research program develops fast and reliable computer software to accelerate the discovery of the genetic causes of CHD, and make personalised genome-based medicine a reality.
Investigating Widespread Regulation Of Gene Expression Through Intron Retention
Funder
National Health and Medical Research Council
Funding Amount
$363,026.00
Summary
We recently discovered a hidden type of gene regulation that appears to be altered in diverse cancers including leukaemia, melanoma and colon cancer. We will explore this widely relevant mechanism using molecular and computational tools. We created the only computer program able to detect this type of regulation and will now share our discovery with cancer scientists through cloud computing technology.