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.
Both human and viral genetic materials (ribonucleic acids, RNA) are made up of 4 different basic residues, namely A, U, G and C. Combination of any three of these ribonucleic acids residues is known as codon , which is essential to target one of the twenty amino acids to the host cell machinery for the making of proteins. Eighteen out of these twenty amino acids can be represented by more than one codon during the making of proteins. Interestingly, human and viral proteins, such as HIV-1, utilis ....Both human and viral genetic materials (ribonucleic acids, RNA) are made up of 4 different basic residues, namely A, U, G and C. Combination of any three of these ribonucleic acids residues is known as codon , which is essential to target one of the twenty amino acids to the host cell machinery for the making of proteins. Eighteen out of these twenty amino acids can be represented by more than one codon during the making of proteins. Interestingly, human and viral proteins, such as HIV-1, utilise two completely different subsets of codons (codon bias) for the synthesis of their respective proteins. The objective of this proposal is to delineate the functional requirement of this codon bias in HIV-1 replication cycle. Results from this work will identify novel elements that may be used for the design of novel antiretroviral strategy. Furthermore, lesson learned from this project will also provide important clues to improve the efficacy and safety of the design of current retroviral gene delivery vector.Read moreRead less
Mapping Of Genetic Traits In Experimental Models Using Databases
Funder
National Health and Medical Research Council
Funding Amount
$237,750.00
Summary
The project aims to detect genes that influence human traits. These traits could be a disease such as diabetes or they may be much less sinister, representing hearing range as an example. Many of these traits are difficult to detect because they are governed by many genes which may also interact with the environment to influence the trait. In order to detect genes in these traits we would like to simplify the complex interactions by eliminating the environment as a potential cause or concentrati ....The project aims to detect genes that influence human traits. These traits could be a disease such as diabetes or they may be much less sinister, representing hearing range as an example. Many of these traits are difficult to detect because they are governed by many genes which may also interact with the environment to influence the trait. In order to detect genes in these traits we would like to simplify the complex interactions by eliminating the environment as a potential cause or concentrating on a particular population where the incidence appears to be much greater. In human populations we have no control over the environmental exposures and we cannot restrict their movements. For this reason many genetic studies have been conducted in mice. Many strains of mice have been generated. Their environment can be strictly controlled, enabling a much better identification of disease genes. Since mice and humans share much of their genome they also share many of their genes and are often afflicted by the same diseases. Thus if we identify genes in mice we have a very good chance of identifying the equivalent human genes. The completion of sequencing for the human genome is being closely followed by the completion of the mouse genome, precisely because mice have been used for over 100 years for genetic studies. The data generated from these sequencing efforts and prior genetic studies is now accumulating in vast databases. These databases of DNA information can be used to map genes for traits. The idea is to determine the trait measurement for many mice in different strains and compare these trait levels to the DNA state (genotype) of markers in the genome of the strains. If these are associated it indicates that the marker is situated close to a gene influencing the trait. This narrows the search considerably. Without this strategy we would have the daunting task of identifiying trait genes from many thousands of potential candidates.Read moreRead less
Roles Of Virus-integrin Interactions And Rotavirus Modulation Of Host Cell Responses In Viral Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$474,000.00
Summary
Rotaviruses are the main cause of severe gastroenteritis in children, and cause 1 in 27 Australian children under the age of 5 years to spend time in hospital. There is currently no rotavirus vaccine available. We aim to discover how rotavirus interacts with host cells. This information is necessary to formulate a safe and effective vaccine, or a therapeutic agent that can block virus growth in host cells. Previously, we showed that rotavirus attaches to cells and enters them using several membe ....Rotaviruses are the main cause of severe gastroenteritis in children, and cause 1 in 27 Australian children under the age of 5 years to spend time in hospital. There is currently no rotavirus vaccine available. We aim to discover how rotavirus interacts with host cells. This information is necessary to formulate a safe and effective vaccine, or a therapeutic agent that can block virus growth in host cells. Previously, we showed that rotavirus attaches to cells and enters them using several members of the integrin protein family that are present on the surface of the cells. Integrins are critical for cell adhesion, survival and communication. In this project, we will identify how rotavirus usage of integrins modulates cell functions. This will help us understand how rotavirus causes disease, how virus spreads in the body and how the immune response defends us from rotavirus. Rotavirus binds integrins using particular stretches of protein sequence that we have shown are also present in other human viral pathogens that cause hepatitis, AIDS and measles. We will determine if these other viruses also recognize integrins.Read moreRead less