ARC Centre for Kangaroo Genome. In this Australian-led Kangaroo Genome Project, we will map and characterize the tammar wallaby genome at the molecular level. Marsupial genomes are uniquely valuable because they provide comparisons that reveal new human genes, regulatory sequences and marsupial-specific genes. These will deliver new products and information useful for medicine, industry, agriculture and conservation. We will construct integrated genetic and physical maps of the genome, clone the ....ARC Centre for Kangaroo Genome. In this Australian-led Kangaroo Genome Project, we will map and characterize the tammar wallaby genome at the molecular level. Marsupial genomes are uniquely valuable because they provide comparisons that reveal new human genes, regulatory sequences and marsupial-specific genes. These will deliver new products and information useful for medicine, industry, agriculture and conservation. We will construct integrated genetic and physical maps of the genome, clone the whole genome as large inserts in BAC vectors, and build a "golden path" with minimal overlap. We will construct libraries of expressed genes from tammar tissues and array them for use in analysing gene expression.Read moreRead less
Designer DNA-binding factors. This project aims to use a natural transcription factor family to enhance the efficiency and functionality of designer DNA-binding factors. Research into the structure and function of zinc finger transcription factors, TAL effectors and CRISPR created designer DNA-binding factors. However, though research has improved the specificity of these factors’ genome-wide binding, their efficacy in regulating the expression of genes requires improvement. Using sequencing, th ....Designer DNA-binding factors. This project aims to use a natural transcription factor family to enhance the efficiency and functionality of designer DNA-binding factors. Research into the structure and function of zinc finger transcription factors, TAL effectors and CRISPR created designer DNA-binding factors. However, though research has improved the specificity of these factors’ genome-wide binding, their efficacy in regulating the expression of genes requires improvement. Using sequencing, the project intends to enhance the efficiency and function of these factors by designing modules to improve the stability of DNA binding and effectiveness in functionally regulating gene expression. The project outcomes could include knowledge enabling the use of genetically engineered DNA-binding proteins to artificially control gene expression, with significant scientific and economic implications.Read moreRead less
Improving Sexual Health In Men With Prostate Cancer: Randomised Controlled Trial Of Exercise And Psychosexual Therapies
Funder
National Health and Medical Research Council
Funding Amount
$583,416.00
Summary
Sexual dysfunction is one of the most common and distressing side effects of prostate cancer. Despite being a critical survivorship care issue, there is a clear gap in knowledge surrounding the optimal treatment of sexual dysfunction in men with prostate cancer. This project examines whether exercise aids in the management of sexual dysfunction and explores if an integrated treatment model incorporating pharmacological, exercise and psychosexual therapies maximises improvement in sexual health.
Targeting Bone Marrow Mediated Angiogenesis And Metastasis In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$463,006.00
Summary
Despite advances in treatment and diagnostics breast cancer (BC) remains one of the leading causes of death in women. Metastases and tumour blood vessel recruitment are linked. Work by Dr Mellick and others has shown that host bone marrow contributes endothelial progenitor cells (EPCs) to tumour vasculature. The chemokines and their receptors, which differentiate EPCs from tumour vessels, will be knocked down in the tumour cells and EPC progenitors with the aim of preventing tumour spread.
Old genes learning new tricks: characterising regulatory changes driving increased heart complexity during vertebrate evolution. The heart has dramatically increased in morphological complexity during vertebrate evolution but the molecular basis driving these major changes remains unknown. Using comparative genomics approaches, this project will explore changes in the regulation of genes involved in heart formation that lead to changes in cardiac structure. It will elucidate for the first time t ....Old genes learning new tricks: characterising regulatory changes driving increased heart complexity during vertebrate evolution. The heart has dramatically increased in morphological complexity during vertebrate evolution but the molecular basis driving these major changes remains unknown. Using comparative genomics approaches, this project will explore changes in the regulation of genes involved in heart formation that lead to changes in cardiac structure. It will elucidate for the first time the cardiac regulatory repertoire in zebrafish and will compare it with that of fly and mouse using cutting-edge bioinformatics pipelines. This work will unravel cardiac-specific regulatory modifications that give rise to evolutionary changes. On a broader scale, it will shed new light on the role of regulatory innovations over gene innovations in the emergence of new traits.Read moreRead less
ADAM Metalloprotease Inhibition For Treatment Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$770,925.00
Summary
Colorectal cancer (CRC) causes over 4000 deaths/year, typically from developing drug resistance and spreading to other organs (metastasis). These processes involve tumour cells called cancer stem cells (CSCs), which rely on specific cell surface proteins for survival and function. We are developing antibodies against one of these type of proteins, to test in mouse models of CRC. These already show promise in targeting CSCs and inhibiting drug-resistance and metastasis in mice.
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
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
A Phase III Trial Comparing Adjuvant Versus Salvage Radiotherapy For High Risk Patients Post Radical Prostatectomy
Funder
National Health and Medical Research Council
Funding Amount
$819,138.00
Summary
About half of all patients Treated with an operation to remove their prostate cancer have a high chance of the cancer coming back. Giving immediate radiotherapy to all patients will improve cure rates but does not benefit all men and can cause significant side effects. This study explores whether it is safe to wait and only give radiotherapy when there is a rising PSA after surgery indicating active cancer. A total of 470 men from Australasia will enter this study comparing the two approaches.
Kruppel-like factors and the methylome. This project aims to test the hypothesis that the KLF/SP family of transcription factors work in part via dynamic interactions with methylated cytosine nucleotides in DNA. This is fundamental to their function as pioneer factors in reprograming and their ability to co-ordinate differentiation and organogenesis. Conversely, dynamic changes in methylation status engage or disengage new regulatory elements in the genome via recruitment of KLF/SP family protei ....Kruppel-like factors and the methylome. This project aims to test the hypothesis that the KLF/SP family of transcription factors work in part via dynamic interactions with methylated cytosine nucleotides in DNA. This is fundamental to their function as pioneer factors in reprograming and their ability to co-ordinate differentiation and organogenesis. Conversely, dynamic changes in methylation status engage or disengage new regulatory elements in the genome via recruitment of KLF/SP family proteins as specific effectors. This project will address a new paradigm in genetics that is likely to underpin development.Read moreRead less