Use Of Expression Profiling To Identify Genes Influencing Cardiovascular Risk In The Norfolk Island Population Isolate
Funder
National Health and Medical Research Council
Funding Amount
$697,409.00
Summary
This study will use a unique population isolate from Norfolk Island. We aim to identify genes that play a role in cardiovascular disease risk. Norfolk has a population of ~1200 permanent residents, most of whom are direct descendents of 18th century English Bounty mutineers and Polynesian women. We will undertake gene expression mapping to identify genomic loci that influence cardiovascular disease using samples from this population isolate.
Investigation Of The Anticancer Action And Cytotoxic-synergism Of Matrix Metalloproteinase Inhibition.
Funder
National Health and Medical Research Council
Funding Amount
$272,036.00
Summary
In virtually all cases, death from solid tumors (including breast cancer) results from invasion and metastasis. The exciting recent pre-clinical observations that a new class of anticancer agents (which primarily target tumour invasion and metastasis) operate synergistically with a number of standard chemotherapy cytotoxics (such as those already used to treat breast cancer) suggests a new and significant additional therapeutic potential for both agents. The basis of this synergism is completely ....In virtually all cases, death from solid tumors (including breast cancer) results from invasion and metastasis. The exciting recent pre-clinical observations that a new class of anticancer agents (which primarily target tumour invasion and metastasis) operate synergistically with a number of standard chemotherapy cytotoxics (such as those already used to treat breast cancer) suggests a new and significant additional therapeutic potential for both agents. The basis of this synergism is completely unknown however, and it is our contention that this mechanism needs to be explored at the molecular level in order to identify which combinations will have most potential in the clinic. This proposal aims to characterize synergistic combinations in an animal model of breast cancer progression, and to determine the specific molecular mechanism of the process. Each phase of the proposed study is a worthwhile undertaking in itself, and while it makes primary use of a breast cancer growth and metastasis system, the information revealed should be relevant to many tumour types. This information can be used to formulate new therapeutic strategies for the treatment of solid tumours and their metastasis in patients.Read moreRead less
Comprehensive transcriptional mapping of emergent division-linked cell fate decisions. This project proposal will lead to a better understanding of the molecular mechanics that drive certain cellular behaviors. To do this, we will use a frontier technology, RNA sequencing, which we think has the potential to revolutionise Australian science and make Australia an even more attractive place for young researchers. The community at large benefits from novel technologies as they create new opportunit ....Comprehensive transcriptional mapping of emergent division-linked cell fate decisions. This project proposal will lead to a better understanding of the molecular mechanics that drive certain cellular behaviors. To do this, we will use a frontier technology, RNA sequencing, which we think has the potential to revolutionise Australian science and make Australia an even more attractive place for young researchers. The community at large benefits from novel technologies as they create new opportunities for university research and attract young minds to the challenges of maths and science.Read moreRead less
I am a molecular biologist determining the mechanisms of eukaryotic mRNA translation and its regulation by RNA-binding proteins and noncoding RNA. In collaborative work I extend these basic science objectives into the medical research areas of cardiology
Evolutionary algorithms for problems in functional genomics data analysis. Skin cancer has a high incidence in the Australian population. Schizophrenia is a psychiatric disorder that affects a significant proportion of the population worldwide. Both illnesses have genetic roots and can be triggered by environmental factors. We will uncover genetic relationship to disease and their responses to environmental conditions using computational methods and mathematical algorithms that can aid in the de ....Evolutionary algorithms for problems in functional genomics data analysis. Skin cancer has a high incidence in the Australian population. Schizophrenia is a psychiatric disorder that affects a significant proportion of the population worldwide. Both illnesses have genetic roots and can be triggered by environmental factors. We will uncover genetic relationship to disease and their responses to environmental conditions using computational methods and mathematical algorithms that can aid in the determination of function, especially in disease states. Understanding the complex genetic interactions that trigger these illnesses would give great benefits in preventive health care, skin cancer and schizophrenia genetic basis, and may lay the ground for building new methods for "personalized medicine".
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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
Genetic dissection of a regulatory deubiquitlyation network. The potential impact of this work is widespread, because although it is known that ubiquitlyation has regulatory consequences in multicellular eukaryotes, individual networks have not been completely described in higher eukaryotes. Knowledge gained about fundamental processes in the A. nidulans model system is directly applicable to fungi used in biotechnology in the food, beverage, enzyme and pharmaceutical production industries, and ....Genetic dissection of a regulatory deubiquitlyation network. The potential impact of this work is widespread, because although it is known that ubiquitlyation has regulatory consequences in multicellular eukaryotes, individual networks have not been completely described in higher eukaryotes. Knowledge gained about fundamental processes in the A. nidulans model system is directly applicable to fungi used in biotechnology in the food, beverage, enzyme and pharmaceutical production industries, and to fungal pathogens. Since the fungal genes that form the basis of this project are conserved in higher eukaryotes including humans, the knowledge will be transferable to these systems. A further benefit that cannot be overstated is the research education and training opportunities provided.
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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.