Matching Between Codon Usage And TRNA Abundance Determines The Expression Of Targeting Genes In Mammalian Cells
Funder
National Health and Medical Research Council
Funding Amount
$358,500.00
Summary
This proposal is about optimal production of protein drugs (biopharmaceuticals), using genetic engineering in the laboratory and gene therapy in patients. It will explore the science behind a novel observation that the optimal way to use the genetic code to encode proteins for production varies from cell to cell in the lab, and from tissue to tissue in patients. If successful, a simple test can be used to decide the optimal genetic code for a specific application.
Investigating The Role Of MtrA In Antimicrobial Resistance Of N. Gonorrhoeae
Funder
National Health and Medical Research Council
Funding Amount
$329,023.00
Summary
The main aim of this project is to investigate how genes are regulated by a specific protein called MtrA. This protein has been involved in antibiotic resistance in Neisseria gonorrhoeae, and has recently been shown to be important for the survival of N. gonorrhoeae in early infections. Understanding the exact mechanisms of this resistance, and how the genes regulated by MtrA are important for early N. gonorrhoeae infections would aid in treatment options.
Microarrays are a new technology for measuring the relative expression levels of thousands of genes simultaneously. They allow medical researchers to take a genome-wide look at which genes are active in a particular tissue type in an organism at a particular time. Many biomedical and biological research groups in Australia have recently untaken microarray experiments for the first time or are planning microarray experiments in the near future. Microarray experiments produce massive amounts of in ....Microarrays are a new technology for measuring the relative expression levels of thousands of genes simultaneously. They allow medical researchers to take a genome-wide look at which genes are active in a particular tissue type in an organism at a particular time. Many biomedical and biological research groups in Australia have recently untaken microarray experiments for the first time or are planning microarray experiments in the near future. Microarray experiments produce massive amounts of information and the study of how to extract this information is still in a fledgling state. This project will solve a number of fundamental problems in microarray data analysis. The emphasis is not on special methods of down-stream analysis but on basic issues which are common to all microarray experiments. The project will determine how tissue samples from different organisms should be combined in complex experiments. It will develop methods for evaluating the quality of results from microarray experiments. It will make microarray analysis less sensitive to production artifacts. It will make novel use of serial analysis of gene expression (SAGE), a more accurate but more expensive and less available technology, to calibrate the results of microarray experiments. The results will be applied during the lifetime of the project to a number of experiments at the Walter and Eliza Hall Institute and the University of Melbourne on blood cell development, cell growth and proliferation, resistance to malaria and leishmaniasis parasites, and Down syndrome.Read moreRead less
Functional Characterisation Of Regulators Of Human Globin Gene Switching
Funder
National Health and Medical Research Council
Funding Amount
$232,131.00
Summary
Red blood cells produce haemoglobin, a tetramer of two alpha globin chains and two beta-globin chains. Haemoglobin reversibly interacts with oxygen in such a way that it efficiently shuttles oxygen between the lungs and the rest of the body. Integrity of the hemoglobin molecule, and red cells which carry it, is essential for life of all organisms with blood. The alpha-globin and beta-globin chains that make up haemoglobin are prodcued by red cell precursors in the bone marrow according to the ge ....Red blood cells produce haemoglobin, a tetramer of two alpha globin chains and two beta-globin chains. Haemoglobin reversibly interacts with oxygen in such a way that it efficiently shuttles oxygen between the lungs and the rest of the body. Integrity of the hemoglobin molecule, and red cells which carry it, is essential for life of all organisms with blood. The alpha-globin and beta-globin chains that make up haemoglobin are prodcued by red cell precursors in the bone marrow according to the genetic blueprint (genes) that are inherited. Genetic disorders resulting from defects in the beta-globin gene are the most common inherited disorders of man. Children who fail to make beta-globin have a disease known as beta-thalassaemia. They are transfusion dependent from ~ 6 months of age and need intensive chelation therapy (infusions) to avoid the serious consequnces of iron overload. The average life expectancy in Western cultures is ~ 30 years. There is no cure. In third world countries where a reliable blood supply is unavailable, death occurs earlier. Patients are aften infected with blood born viruses such as hepatitis B, hepatitis C and the AIDS virus, HIV. Sickle cell anaemia is also a very common disease. It is due to a single DNA base mutation at in the beta-globin gene that results in production of normal amounts of a defective beta-globin molecule (HbS). In low oxygen, HbS molecules polymerize in red cells and irreversibly damage them. These red cells get trapped in small blood capillaries throughout the circulation causing small infarcts which results in severe pain and organ damage. The life expectancy is <2 years in the thrid world and ~20-30 years in the west. The irony of these two diseases is that there is a perfectly normal fetal globin gene that has been silenced during fetal life. This grant aims to understand the mechanism of the switch from fetal to adult globin gene usage so it can be reversed in adults with b-thalassemia and sickle cell diseaseRead moreRead less
Identification Of Critical Regulatory Elements In The BRCA1 Gene
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Breast cancer affects approximately one in ten women and is therefore a major health problem. In order to improve the diagnosis, treatment and prognosis of this disease, it is critical to understand the molecular defects that contribute to disease initiation and progression. Over the last twenty years significant progress has been made in this regard, however there still remain a considerable number of unanswered questions. For example, it is not yet clear precisely what contribution each of the ....Breast cancer affects approximately one in ten women and is therefore a major health problem. In order to improve the diagnosis, treatment and prognosis of this disease, it is critical to understand the molecular defects that contribute to disease initiation and progression. Over the last twenty years significant progress has been made in this regard, however there still remain a considerable number of unanswered questions. For example, it is not yet clear precisely what contribution each of these genes makes. This is largely due to limitations in current mutation detection strategies and an incomplete understanding of all of the genetic elements for which disruption can lead to loss of gene function. This propsal aims to identify all of the genetic elements critical for the expression of an important breast cancer gene called BRCA1. Furthermore, it aims to determine the status of these elements in breast cancer patients, thus expanding our knowledge of the actual contribution disruption of this gene makes to this disease.Read moreRead less