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Cloning Of Human NK Cells And Macrophages Carbohydrate Receptors
Funder
National Health and Medical Research Council
Funding Amount
$489,750.00
Summary
Lymphocytes, also known as white blood cells, are important for the well being of all individuals as these are the cells which fight infection by microorganisms. The lymphocyte gets its information about enviroment and communicates with other cells using molecules on the cell surface. We are examining a group of molecules found on the surface of different lymphocytes which bind different sugars, and also to characterised new cell surface molecules that interact with carbohydrates. These studies ....Lymphocytes, also known as white blood cells, are important for the well being of all individuals as these are the cells which fight infection by microorganisms. The lymphocyte gets its information about enviroment and communicates with other cells using molecules on the cell surface. We are examining a group of molecules found on the surface of different lymphocytes which bind different sugars, and also to characterised new cell surface molecules that interact with carbohydrates. These studies will examine the structure of the the molecules that interact with with sugars, in order to understand how these give messages to the lymphocyte to trigger various functions that these cell perform in the immune response. We will isolate the genes for these and study their function in greater detail. The cell surface carbohydrate receptors represents several different families of molecules, it is highly likely that these have important roles in the immune response. The potential significance of studying these lymphocyte cell surface molecules is in defining the functional properties of these molecules, the results of which will give us novel insights into the molecular mechanisms involved in the generation of immune responses, the mechanism of immuno deficiency and autoimmunity.Read moreRead less
Epigenetic Therapies To Differentiate And Eradicate Leukaemia Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$674,315.00
Summary
Leukemia stem cells (LSC) are often resistant to conventional and targeted therapies and therefore serve as the seed for leukaemia relapse. The overall aim of this project is to use small molecule therapies to block the activity of a particular protein (LSD1) in LSC in order to differentiate them and expose a vulnerability to another epigenetic therapy called a BET inhibitor. Together, these epigenetic therapies will differentiate and eradicate LSC, leading to improved outcome in AML.
Chromosomal translocations in the MLL gene results in aggressive leukaemias. Several drugs developed to target proteins that interact with the MLL fusion proteins are now being tested in the clinic. Despite this progress, our understanding of how the MLL fusion proteins cause leukaemia remains incomplete. In particular, it is unclear how the MLL fusion protein drives the development of leukaemia. In this project I will address these important issues with cell and molecular biology methods.
EEF1A1 Is Critical For HIV-1 Reverse Transcription And Replication
Funder
National Health and Medical Research Council
Funding Amount
$521,429.00
Summary
The project will investigate interaction between the AIDS virus, HIV-1, and the human cell it grows in specifically focusing on a human protein called eEF1A. Our research shows eEF1A is required for HIV-1 growth by regulating a step in the virus life cycle called reverse transcription. The goal of this project is investigate how interaction with eEF1A helps HIV-1 reverse transcription and to find drugs that block HIV-1 interaction with eEF1A.
Unravelling transthyretin amyloid, bounding ahead using wallabies. Each protein in our body has a unique shape that enables it to function correctly. For unknown reasons, some proteins can change their shape, aggregate with other proteins and stick to the outside of cells of major organs or nerves. This prevents those cells from working properly and results in disease. Transthyretin is a protein that changes shape and aggregates in the heart of most people over the age of 70. The disease is call ....Unravelling transthyretin amyloid, bounding ahead using wallabies. Each protein in our body has a unique shape that enables it to function correctly. For unknown reasons, some proteins can change their shape, aggregate with other proteins and stick to the outside of cells of major organs or nerves. This prevents those cells from working properly and results in disease. Transthyretin is a protein that changes shape and aggregates in the heart of most people over the age of 70. The disease is called Senile Systemic Amyloidosis (SSA). It is not known how or why this happens. There is no cure or therapy. This project will use transthyretins from human and wallaby to explore a possible cause of SSA. If our hypothesis is correct, we will propose preventative actions to reduce the incidence of SSA in the future.Read moreRead less
Structure and temperature adaptation of chaperonin TF55 from Sulfolobus solfataricus. Our work has future potential both for biotechnology and for medical therapies. The cages formed by chaperonin subunits and their ability to bind to specific targets could lead to their application as nano-vesicles, could facilitate expression of eukaryotic proteins in bacteria and could help to prevent or dissolve protein aggregates. With Australia's ageing population, we can expect an increasing prevalence of ....Structure and temperature adaptation of chaperonin TF55 from Sulfolobus solfataricus. Our work has future potential both for biotechnology and for medical therapies. The cages formed by chaperonin subunits and their ability to bind to specific targets could lead to their application as nano-vesicles, could facilitate expression of eukaryotic proteins in bacteria and could help to prevent or dissolve protein aggregates. With Australia's ageing population, we can expect an increasing prevalence of pathologies such as Alzheimer's and Parkinson's disease and other diseases that arise from protein mis-folding and aggregation, including myopathies and cataracts. A participation of chaperonins has been implicated in these age-related diseases and demands detailed structural and functional investigations.Read moreRead less
Molecular Characterisation Of Lipid Droplet Function
Funder
National Health and Medical Research Council
Funding Amount
$496,446.00
Summary
Fat is stored inside cells in spherical structures called lipid droplets. The accumulation of fat within lipid droplets underlies obesity. This project aims to understand how fat is stored within lipid droplets and how it is released when energy is required. In particular, we will look at two types of protein which move to lipid droplets under certain energy conditions and attempt to unravel how these proteins control fat storage and release. The first protein we will study, caveolin, normally a ....Fat is stored inside cells in spherical structures called lipid droplets. The accumulation of fat within lipid droplets underlies obesity. This project aims to understand how fat is stored within lipid droplets and how it is released when energy is required. In particular, we will look at two types of protein which move to lipid droplets under certain energy conditions and attempt to unravel how these proteins control fat storage and release. The first protein we will study, caveolin, normally associates with regions of the cell surface but moves to lipid droplets when cells are fed lipids. Mice which lack this protein eat more food but remain leaner than normal mice. Understanding how caveolin moves to lipid droplets and how it controls fat accumulation will therefore provide new insights into obesity and conditions associated with obesity, such as diabetes. The second protein to be studied, Rab18, is a member of a protein family which controls membrane movement within cells. Rab18 moves to lipid droplets when lipid release is stimulated. Therefore studies of Rab18 can provide new insights into the way lipids are released from fat tissue under conditions of starvation. The project will provide fundamental new insights into the basic mechanisms by which we store energy and the energy imbalances which cause obesity and related diseases.Read moreRead less
The Mechanism Of Tat-enhanced Reverse Transcription In HIV-1
Funder
National Health and Medical Research Council
Funding Amount
$282,750.00
Summary
During reverse transcription, the positive-strand HIV-1 RNA genome is converted into a double-stranded DNA copy which can be permanently insert into the host cell genome. Many HIV-1 proteins including Tat contribute to the efficiency of reverse transcription. There are two competing hypotheses to explain how Tat enhances reverse transcription. The indirect mechanism hypothesis holds that Tat-enhanced reverse transcription is due to the combined effects of the Tat-induced expression of cellular g ....During reverse transcription, the positive-strand HIV-1 RNA genome is converted into a double-stranded DNA copy which can be permanently insert into the host cell genome. Many HIV-1 proteins including Tat contribute to the efficiency of reverse transcription. There are two competing hypotheses to explain how Tat enhances reverse transcription. The indirect mechanism hypothesis holds that Tat-enhanced reverse transcription is due to the combined effects of the Tat-induced expression of cellular genes. The direct mechanism hypothesis is that Tat functions directly during RTN, implying it is a virion protein. Our recent genetic and biochemical data provide strong evidence that a novel form of Tat, which we call vTat, has a direct role in RTN. This proposal will investigate these two leading hypotheses. Given the enormity of the HIV pandemic and the many recent reports from the United States that most patient isolated virus is resistant to at least one antiretroviral drug, these studies have as an outcome the identification and characterisation of important new key molecules towards which antiretroviral strategies can be designed.Read moreRead less
Remodelling encapsulin nanocages to help enhance plant carbon fixation. Nature has evolved mechanisms in microbial systems to improve photosynthetic efficiency by saturating the enzyme Rubisco with carbon dioxide. These carbon concentrating mechanisms are genetically complex, precluding successful introduction into crops. Our simpler approach is to use encapsulins, a new source of robust bacterial pore-containing nanocages made from a single gene. This project will optimise the development of sy ....Remodelling encapsulin nanocages to help enhance plant carbon fixation. Nature has evolved mechanisms in microbial systems to improve photosynthetic efficiency by saturating the enzyme Rubisco with carbon dioxide. These carbon concentrating mechanisms are genetically complex, precluding successful introduction into crops. Our simpler approach is to use encapsulins, a new source of robust bacterial pore-containing nanocages made from a single gene. This project will optimise the development of synthetic encapsulin-Rubisco carbon-fixing nanoreactors and transform them into leaf chloroplasts to test their impact on plant photosynthesis and growth. Our genetically simpler solution will aid ongoing global efforts to deliver overdue step change improvements in agricultural productivity.Read moreRead less
Identifying novel salinity tolerance mechanisms by spatial and temporal analysis of lipids in barley. Agrifood production faces the dual challenges of an increasing world population and the threats of abiotic stresses arising from climate change and the erosion of arable land. Cereals, the major food crops, are poorly adapted to tolerate most abiotic stresses, including salinity. This project applies new technologies investigating spatial and temporal biochemical mechanisms a model cereal, Horde ....Identifying novel salinity tolerance mechanisms by spatial and temporal analysis of lipids in barley. Agrifood production faces the dual challenges of an increasing world population and the threats of abiotic stresses arising from climate change and the erosion of arable land. Cereals, the major food crops, are poorly adapted to tolerate most abiotic stresses, including salinity. This project applies new technologies investigating spatial and temporal biochemical mechanisms a model cereal, Hordeum vulgare (barley), utilises to adapt and tolerate salinity. The aims are to investigate the role of specifically plasma membrane lipids modulating either signalling pathways or membrane fluidity that impacts on adaptation during salinity. The results will provide new leads for the development of cereal germplasm with increased salt tolerance.Read moreRead less