DNA end resection: from basic mechanisms to genome editing. The project aims to understand processes underlying genome editing, a bioengineering process that introduces specific mutations into genomic DNA. Homologous recombination and nonhomologous end-joining pathways play a crucial role in repairing broken DNA strands, which are a toxic form of DNA damage. The proteins that function in the repair process have been recently identified, but it remains unclear how they function on a mechanistic l ....DNA end resection: from basic mechanisms to genome editing. The project aims to understand processes underlying genome editing, a bioengineering process that introduces specific mutations into genomic DNA. Homologous recombination and nonhomologous end-joining pathways play a crucial role in repairing broken DNA strands, which are a toxic form of DNA damage. The proteins that function in the repair process have been recently identified, but it remains unclear how they function on a mechanistic level and how either of the two main pathways is selected. The project aims to define how the activity of a key control protein, Sae2 (Sporulation in the Absence of Spo Eleven), is regulated by posttranslational modifications, and how this activates homologous recombination. The project plans to first use Saccharomyces cerevisiae yeast as a model and then to extend research into the human system in an attempt to improve the efficiency of genome editing. Read moreRead less
The “New” Biochemistry of Polyamines: When Metabolic Pathways Collide. Basic biochemistry and the metabolic regulation of proliferation remain as the fundamental building blocks of knowledge in cell biology that have enabled breakthrough advances in biology and medicine. Polyamines are unique and ubiquitous low-Mr amines that play vital roles in many biological processes, including proliferation, DNA/RNA synthesis, etc. This proposal will mechanistically dissect the "new" biochemistry of polyami ....The “New” Biochemistry of Polyamines: When Metabolic Pathways Collide. Basic biochemistry and the metabolic regulation of proliferation remain as the fundamental building blocks of knowledge in cell biology that have enabled breakthrough advances in biology and medicine. Polyamines are unique and ubiquitous low-Mr amines that play vital roles in many biological processes, including proliferation, DNA/RNA synthesis, etc. This proposal will mechanistically dissect the "new" biochemistry of polyamines, as we have discovered that polyamines are regulated by iron at 2-major levels, involving >10-key polyamine pathway proteins. This proposal represents first-in-field studies specifically designed to dissect mechanisms involved in this relationship. Our Central Hypothesis is that iron regulates polyamine metabolism.Read moreRead less
Understanding how RNA editing regulates RNA fate. This project aims to address how RNA editing mediated by ADAR1 alters the interactions of targeted RNA with the innate immune sensing system. ADAR1 editing converts adenosine to inosine within double stranded RNA. It is known that this is key to prevent activation of the innate immune sensor MDA5 by endogenous RNA. However, we do not understand why edited RNA is tolerated and unedited RNA is not. This project will generate new knowledge regarding ....Understanding how RNA editing regulates RNA fate. This project aims to address how RNA editing mediated by ADAR1 alters the interactions of targeted RNA with the innate immune sensing system. ADAR1 editing converts adenosine to inosine within double stranded RNA. It is known that this is key to prevent activation of the innate immune sensor MDA5 by endogenous RNA. However, we do not understand why edited RNA is tolerated and unedited RNA is not. This project will generate new knowledge regarding the effect of editing on how endogenous RNA is perceived by the innate immune system.Read moreRead less
Development of a non-invasive diagnostic test of Embryo Viability. A successful outcome will:
. improve the cost effectiveness of assisted reproductive technologies resulting in reduced health care costs and allowing greater use of ART in animal production
. by greater cost-effectiveness, facilitate greater access to these advanced technologies in less well developed economies
. build the national capacity in development and validation of biotech diagnostics
. build collaborative relationsh ....Development of a non-invasive diagnostic test of Embryo Viability. A successful outcome will:
. improve the cost effectiveness of assisted reproductive technologies resulting in reduced health care costs and allowing greater use of ART in animal production
. by greater cost-effectiveness, facilitate greater access to these advanced technologies in less well developed economies
. build the national capacity in development and validation of biotech diagnostics
. build collaborative relationship between the CI, University of Sydney and a leading industry partner (Cook Australia)
. lead to significant new fundamental knowledge in embryology that will be of major International significance
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Special Research Initiatives - Grant ID: SR0354892
Funder
Australian Research Council
Funding Amount
$40,000.00
Summary
The Australian Protease Network. Proteases are pivotal enzymes during birth, life, ageing and death of all organisms. Proteases regulate most physiological processes by controlling protein activation, synthesis and turnover and are essential for replication and spread of viruses, bacteria and parasites that cause infectious diseases. Blockbuster drugs and diagnostics already target a few proteases. Australians have made innovative contributions individually to understanding and regulating these ....The Australian Protease Network. Proteases are pivotal enzymes during birth, life, ageing and death of all organisms. Proteases regulate most physiological processes by controlling protein activation, synthesis and turnover and are essential for replication and spread of viruses, bacteria and parasites that cause infectious diseases. Blockbuster drugs and diagnostics already target a few proteases. Australians have made innovative contributions individually to understanding and regulating these enzymes. However this initiative aims to network their efforts by value-adding to the current protease research through promoting national and international collaborations to improve our understanding of biology, and encourage exploitation of proteases/inhibitors/receptors for pharmaceutical and industrial applications.Read moreRead less
Regulation of cell surface sialylation by targeting the CMP-sialic acid transporter and sialyltransferase: Towards the development of anti-metastatic agents. The mortality rates for many of the cancers afflicting the world's population are mirrored in Australia, particularly colon cancer. It's generally accepted that colon cancer, and cancers as a whole, are a significant healthcare issue in this country, representing a major challenge to biomedical researchers and healthcare professional. The e ....Regulation of cell surface sialylation by targeting the CMP-sialic acid transporter and sialyltransferase: Towards the development of anti-metastatic agents. The mortality rates for many of the cancers afflicting the world's population are mirrored in Australia, particularly colon cancer. It's generally accepted that colon cancer, and cancers as a whole, are a significant healthcare issue in this country, representing a major challenge to biomedical researchers and healthcare professional. The economic and social impact is immense, placing a huge strain on the healthcare system, as well as on the families affected. Any alternative treatment reducing cancer metastasis would be of enormous national and international benefit. It's believed that the significant studies outlined in this proposal, which are based on exciting preliminary data, will make a sizeable contribution to achieving this goal.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE170100021
Funder
Australian Research Council
Funding Amount
$2,168,000.00
Summary
Australian Metabolic Phenotyping Centre (AMPC). This project aims to establish a centre for targeted and exploratory metabolic phenotyping. Metabolic phenotyping quantitatively measures the precursors, intermediates and products of metabolism interacting within a biological system. This project will use high-resolution spectrometry and spectroscopy to generate comprehensive, multi-parameter metabolite data sets for biological samples at the population level, at unprecedented throughput and low c ....Australian Metabolic Phenotyping Centre (AMPC). This project aims to establish a centre for targeted and exploratory metabolic phenotyping. Metabolic phenotyping quantitatively measures the precursors, intermediates and products of metabolism interacting within a biological system. This project will use high-resolution spectrometry and spectroscopy to generate comprehensive, multi-parameter metabolite data sets for biological samples at the population level, at unprecedented throughput and low cost, to address biological and biomedical research needs. This project is expected to make Australian scientists globally competitive in the life sciences including biological, clinical and biomedical, plant and crop sciences, analytical chemistry, toxicology, agriculture, wildlife conservation and sports science, and to drive advances in the data sciences for systems biology.Read moreRead less
Identification of novel biomarkers in tears for prostate cancer diagnosis and prognosis. The purpose of this study is to identify novel biomarkers in the tears of patients with CaP. The use of the several techniques will increase the chance of success and enable us to find more diagnostic markers. If successful, the identified proteins may be used to diagnose and determine the stage of cancer. This will help guide clinicians in choosing the best treatment methods for an individual patient. The m ....Identification of novel biomarkers in tears for prostate cancer diagnosis and prognosis. The purpose of this study is to identify novel biomarkers in the tears of patients with CaP. The use of the several techniques will increase the chance of success and enable us to find more diagnostic markers. If successful, the identified proteins may be used to diagnose and determine the stage of cancer. This will help guide clinicians in choosing the best treatment methods for an individual patient. The markers may also be used to monitor the disease progress and the effects of treatment. The results from this study may improve the prognosis of CaP patients.Read moreRead less
Targeting the undruggable: epitope mapping using Phylomers peptides to modulate activity of Transcription Factors. This project aims at expanding the pool of drug targets, by extending drug screening to protein-protein interaction networks. This project aims to assemble a novel technical platform to detect binding between proteins, using a combination of cell-free protein expression, AlphaScreen and single-molecule fluorescence. This pipeline has great potential to accelerate the exploration of ....Targeting the undruggable: epitope mapping using Phylomers peptides to modulate activity of Transcription Factors. This project aims at expanding the pool of drug targets, by extending drug screening to protein-protein interaction networks. This project aims to assemble a novel technical platform to detect binding between proteins, using a combination of cell-free protein expression, AlphaScreen and single-molecule fluorescence. This pipeline has great potential to accelerate the exploration of protein networks, and provides also a generic platform for drug screening on difficult targets. The project intends to screen Phylogica's libraries of peptides called Phylomers to discover tight binders to a Transcription Factor, Sox18. The objective of this project is to determine which Phylomers can disrupt specific interactions between Sox18 and its binding partners involved in lymphangiogenesis.Read moreRead less
A microfluidic array of phylomers for rapid discovery of peptide probes and biomarkers. This project, through an alliance with Phylogica, aims at exploiting a unique source of structural diversity for drug discovery, harvesting the creativity of nature in its most exotic places. The project will develop a novel approach to validate design and validate drug candidates, by gathering them on a single screening chip for a powerful discovery platform.