Discovery Early Career Researcher Award - Grant ID: DE170100506
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
Specialised ribosomes: An unexplored regulatory layer to tune the proteome. This project aims to decipher human ribosome composition across tissues and conditions, and regulate its composition and activity (selective translation of subsets of transcripts) in a tissue-dependent, spatial and temporal manner – a major challenge in biology. Although ribosomes have been historically thought of as uniform entities, recent evidence suggests that their composition might be regulated. Elevating the expre ....Specialised ribosomes: An unexplored regulatory layer to tune the proteome. This project aims to decipher human ribosome composition across tissues and conditions, and regulate its composition and activity (selective translation of subsets of transcripts) in a tissue-dependent, spatial and temporal manner – a major challenge in biology. Although ribosomes have been historically thought of as uniform entities, recent evidence suggests that their composition might be regulated. Elevating the expression of a target protein without affecting mRNA levels is expected to benefit other disciplines, including biotechnology (e.g. recombinant protein expression), biomedicine (e.g. treatment of a human disease by suppression or enhancement of the levels of key disease-related proteins) and synthetic biology.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE220101210
Funder
Australian Research Council
Funding Amount
$451,634.00
Summary
Deciphering molecular genetic mechanisms underlying chromatin interactions. This project aims to generate the high confidence map of enhancer-promoter links in 61 tissues and cells through robust integration of novel machine learning tools with genomic and epigenomic datasets. Understanding which key elements in the genome may be important to fine-tune gene expression is essential for understanding biological pathways. The expected outcomes include i) New tools to robustly identify true chromati ....Deciphering molecular genetic mechanisms underlying chromatin interactions. This project aims to generate the high confidence map of enhancer-promoter links in 61 tissues and cells through robust integration of novel machine learning tools with genomic and epigenomic datasets. Understanding which key elements in the genome may be important to fine-tune gene expression is essential for understanding biological pathways. The expected outcomes include i) New tools to robustly identify true chromatin pairs; ii) Comperehensive maps of regulatory interactomes in 61 tissues & cells, which will provide a roadmap for interpreting & prioritising noncoding variants.
This should provide significant benefit to Australia's capacity for cutting-edge genomics research through fundamental understanding of gene regulation mechanism.Read moreRead less
From the pouch to the grave: age and sex related changes in immunity in the Tasmanian devil. Tasmanian devils face extinction in the wild due to the emergence of a contagious cancer: Devil Facial Tumour Disease (DFTD). A comprehensive understanding of the devil immune system is necessary to better understand the disease and develop a vaccine against it. This project will characterise immune responses of healthy devils throughout life, from the pouch, to onset of puberty, to old age. This project ....From the pouch to the grave: age and sex related changes in immunity in the Tasmanian devil. Tasmanian devils face extinction in the wild due to the emergence of a contagious cancer: Devil Facial Tumour Disease (DFTD). A comprehensive understanding of the devil immune system is necessary to better understand the disease and develop a vaccine against it. This project will characterise immune responses of healthy devils throughout life, from the pouch, to onset of puberty, to old age. This project will then compare these responses in DFTD-affected devils to determine why DFTD affects older animals first and does not affect sexually-immature devils. Additional outcomes will include the development of novel antibiotics against human and animal diseases and an atlas of devil development using the latest imaging technologies.Read moreRead less
Whole-genome multivariate reaction norm model for complex traits. This project aims to develop a multivariate whole-genome genotype-covariate correlation and interaction model that can be applied to a wide range of existing genome-wide association study (GWAS) datasets. Genotype-covariate correlation and interaction (GCCI) are fundamental in biology but there is no standard approach to disentangle interaction from correlation in the whole-genome analyses. This project will address the key featur ....Whole-genome multivariate reaction norm model for complex traits. This project aims to develop a multivariate whole-genome genotype-covariate correlation and interaction model that can be applied to a wide range of existing genome-wide association study (GWAS) datasets. Genotype-covariate correlation and interaction (GCCI) are fundamental in biology but there is no standard approach to disentangle interaction from correlation in the whole-genome analyses. This project will address the key feature in biology, which relates to dissecting the complex mechanism of association and interaction. The proposed statistical model implemented in a context of a novel design based on multiple GWAS data sets is a paradigm shifting-tool with applications to multiple industries.Read moreRead less
Evolution and function of mammalian sex chromosomes. Research on iconic Australian mammals has profoundly reshaped our understanding of reproductive biology and sex chromosome evolution. In this project we combine unique expertise, international collaboration and novel genetic information about Australia's unique egg-laying mammals (echidna and platypus) to investigate major aspects of reproduction. This work will address fundamental aspects of sex chromosome biology and advance our understandin ....Evolution and function of mammalian sex chromosomes. Research on iconic Australian mammals has profoundly reshaped our understanding of reproductive biology and sex chromosome evolution. In this project we combine unique expertise, international collaboration and novel genetic information about Australia's unique egg-laying mammals (echidna and platypus) to investigate major aspects of reproduction. This work will address fundamental aspects of sex chromosome biology and advance our understanding of mammalian reproduction. The knowledge gained will have application in captive breeding and conservation of these extraordinary Australian mammals. The project also provides opportunity to train research students in cutting edge molecular biology and informatics.Read moreRead less
Complex trait analyses based on genome-wide approaches. This project aims to develop whole genome approaches that can improve the estimation and prediction power by using information from the dynamic genetic architecture of complex traits (i.e. the changes of genetic characteristics and effects when varying effective population size and genetic backgrounds). The project intends to deliver advanced statistical models, efficient algorithms and design by combining data from close relatives, populat ....Complex trait analyses based on genome-wide approaches. This project aims to develop whole genome approaches that can improve the estimation and prediction power by using information from the dynamic genetic architecture of complex traits (i.e. the changes of genetic characteristics and effects when varying effective population size and genetic backgrounds). The project intends to deliver advanced statistical models, efficient algorithms and design by combining data from close relatives, population samples or from different populations (e.g. multi-ethnicities or multi-breeds). The expected outcome is to better understand the dynamic architecture of complex traits and develop methods with improved power, precision and accuracy in genomic analyses.Read moreRead less
The mucosal immune system of fish: analysis of the immune repertoire in gut-and gill-associated lymphoid tissues in trout. Infectious disease causes major economic loss to the aquaculture industry, highlighting the need for effective vaccination strategies. While oral or immersion vaccination represents the most cost effective means of protecting fish against infectious disease there are problems associated with inducing an effective immune response in fish that will assist our industry partner ....The mucosal immune system of fish: analysis of the immune repertoire in gut-and gill-associated lymphoid tissues in trout. Infectious disease causes major economic loss to the aquaculture industry, highlighting the need for effective vaccination strategies. While oral or immersion vaccination represents the most cost effective means of protecting fish against infectious disease there are problems associated with inducing an effective immune response in fish that will assist our industry partner (Novartis Animal Vaccines Ltd) to develop improved fish vaccines. The project will provide postgraduate training in the area of fish immunology that is vital to the developing Australian aquaculture industry.Read moreRead less
The transcriptional co-repressor C-terminal Binding Protein (CtBP) in metabolic control. This project will provide insights into the genes that regulate the storage of fat. We will learn about basic biology but will also discover mechanisms that may be used to influence fat storage in human health. We will also consolidate Australia's expertise in the use of the genetic model organism, the worm C. elegans, and validate the findings in mammalian systems. Finally, the process of training young sci ....The transcriptional co-repressor C-terminal Binding Protein (CtBP) in metabolic control. This project will provide insights into the genes that regulate the storage of fat. We will learn about basic biology but will also discover mechanisms that may be used to influence fat storage in human health. We will also consolidate Australia's expertise in the use of the genetic model organism, the worm C. elegans, and validate the findings in mammalian systems. Finally, the process of training young scientists in these modern systems, will also equip future researchers to make additional contributions to Australia's research output.Read moreRead less
RNA splicing: factors and mechanisms. Most primary gene transcripts must have their noncoding intronic sequences spliced out before the mRNA can be translated. Moreover, alternative splicing enables cells to generate a far more proteins than there are genes in the nucleus. Based on our proven success with ZNF265 we will isolate novel RNA interactors and their partners, colocalize these in intranuclear compartments, and elucidate their effect on pre-mRNA splicing. This will provide timely spin-of ....RNA splicing: factors and mechanisms. Most primary gene transcripts must have their noncoding intronic sequences spliced out before the mRNA can be translated. Moreover, alternative splicing enables cells to generate a far more proteins than there are genes in the nucleus. Based on our proven success with ZNF265 we will isolate novel RNA interactors and their partners, colocalize these in intranuclear compartments, and elucidate their effect on pre-mRNA splicing. This will provide timely spin-offs to the Human genome Project and EST sequence information, where the finding of only approx. 30,000 genes in our genome highlights the important role of alternative splicing in generating the large proteome repertoire of cells. This will bring considerable benefits to science, society, and the biotech industry.Read moreRead less
A new mechanism of gene regulation. This project will advance our knowledge of how genes are switched on and off, by focusing on a very common class of gene regulatory proteins known as zinc finger proteins. The results of this study will improve our understanding of the fundamental molecular events that underpin gene regulation and how we might control it in fields such as biotechnology and gene therapy.