Retromer directs membrane protein trafficking within the endosome. The exposure of proteins to the extracellular environment is dependent on how the travel through the various regions of the cell. The work will lead to a richer understanding of how this process is regulated by protein complexes. These complexes act within cells to drive the formation of membrane transport tubules containing cargo molecules.
Making muscle: molecular dissection of membrane domain formation. For a muscle to contract efficiently in response to an electrical signal it requires the formation of an extensive system of hollow membranous tubules through which the signal can be propagated. This proposal addresses the molecular mechanisms involved in the formation of this tubule system in skeletal muscle. This project will develop cell biology in a whole organism rather than a cell culture system and provide a new framework f ....Making muscle: molecular dissection of membrane domain formation. For a muscle to contract efficiently in response to an electrical signal it requires the formation of an extensive system of hollow membranous tubules through which the signal can be propagated. This proposal addresses the molecular mechanisms involved in the formation of this tubule system in skeletal muscle. This project will develop cell biology in a whole organism rather than a cell culture system and provide a new framework for Australian and international cell biologists. It will generate new knowledge, train young Australian scientists, help build international collaborative networks and engage the public outside the research community.Read moreRead less
Myofibroblast differentiation: from haemopoietic cells to smooth muscle. Until very recently the ability of adult cells with specific differentiated functions to re-differentiate for another function was thought to be extremely limited. However we have shown that cells ultimately derived from the bone marrow can differentiate into fibroblasts, then into myofibroblasts and then into smooth muscle cells. This project will build on these unique findings and determine the molecular mechanisms cont ....Myofibroblast differentiation: from haemopoietic cells to smooth muscle. Until very recently the ability of adult cells with specific differentiated functions to re-differentiate for another function was thought to be extremely limited. However we have shown that cells ultimately derived from the bone marrow can differentiate into fibroblasts, then into myofibroblasts and then into smooth muscle cells. This project will build on these unique findings and determine the molecular mechanisms controlling this process. We hypothesise that the local environment of a cell is critical and will involve a combination of particular extracellular matrix and growth factors as well as mechanical tension and the presence of other cell types.Read moreRead less
Structural And Functional Analysis Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
We seek to understand the mechanisms by which genes are switched on and off throughout our lifetime. A number of multi-component protein machines are involved in this process but their make-up and mechanism of action is not understood. We will investigate the structure and function of one of these machines that has been strongly linked to cancer.
Combined genetic and cellular analysis of melanisation to study variation in human pigmentation. This investigation examines variations in the genes that are important determinants of human skin pigmentation and are likely to be associated with skin cancer risk. Our research program will form the basis of future diagnostics based on major genes that determine a persons skin type. Current skin cancer prevention strategies rely predominantly on broad spectrum campaigns that are aimed at increasi ....Combined genetic and cellular analysis of melanisation to study variation in human pigmentation. This investigation examines variations in the genes that are important determinants of human skin pigmentation and are likely to be associated with skin cancer risk. Our research program will form the basis of future diagnostics based on major genes that determine a persons skin type. Current skin cancer prevention strategies rely predominantly on broad spectrum campaigns that are aimed at increasing the general community awareness of the damaging effects of UV radiation. A better understanding of the genetic basis of UV-sensitive skin types will greatly enhance the targeting of such skin cancer-prevention campaigns, provide an understanding of changes that occur in skin pathology, and the mechanisms of sun induced tanning.Read moreRead less
Parallel genetic and cellular analysis of melanogensis: A new paradigm to study variation in pigmentation. This is the first attempt to characterise the differences in human pigmentation using a combined genetic and cellular analysis of melanogenesis. We have the ability to culture the pigmenting cells of the human epidermis and hair follicles called melanocytes from individuals of defined genotype. This will allow us to correlate mutations in melanosomal proteins with functional defects withi ....Parallel genetic and cellular analysis of melanogensis: A new paradigm to study variation in pigmentation. This is the first attempt to characterise the differences in human pigmentation using a combined genetic and cellular analysis of melanogenesis. We have the ability to culture the pigmenting cells of the human epidermis and hair follicles called melanocytes from individuals of defined genotype. This will allow us to correlate mutations in melanosomal proteins with functional defects within the cells in culture using live cell imaging, electron microscopy and biochemical analysis. This will provide a molecular basis to explain the pigmentary characteristics of individuals allowing prediction and diagnosis of their photosensitivity with important implications for skin cancer risk.Read moreRead less
The endosome at atomic resolution. The project seeks to improve understanding of intracellular transport. The transport of proteins is essential for controlling the interactions of a cell with its environment, and for regulating a huge number of cell signalling events. The retromer protein complex is a central mediator of intracellular trafficking in organelles called endosomes. It is vital for normal cell homeostasis in all eukaryotic organisms, and is an emerging target for treatment of human ....The endosome at atomic resolution. The project seeks to improve understanding of intracellular transport. The transport of proteins is essential for controlling the interactions of a cell with its environment, and for regulating a huge number of cell signalling events. The retromer protein complex is a central mediator of intracellular trafficking in organelles called endosomes. It is vital for normal cell homeostasis in all eukaryotic organisms, and is an emerging target for treatment of human neurodegenerative diseases. This project plans to use a combination of cutting-edge X-ray crystallographic and electron microscopy approaches to develop a multi-scale, pseudo-atomic structure of retromer and key regulatory proteins to understand how this multi-component protein machinery is assembled to control intracellular transport.Read moreRead less
Regulation of human immunodeficiency virus type 1 (HIV-1) replication by viral and cellular proteins. Using a mouse model, human cells will be treated with a very powerful antiviral protein using a gene therapy approach so as to block the human immunodeficiency virus (HIV) from growing. By learning how this antiviral protein works, this project will assist in the development of new strategies to treat HIV infection.
Structural analysis of a novel plasma membrane coat complex. The plasma membrane of mammalian cells forms a crucial barrier between the cell and the outside world. This project investigates how a newly-discovered family of proteins work together to generate specialised regions of the plasma membrane called caveolae.
Structural basis for the assembly of caveolae. Caveolae are small invaginations of the plasma membrane and are a characteristic feature of eukaryotic cells. Described morphologically in the early 1950s their many important functions are only just beginning to be revealed. Caveolae are multifunctional organelles that play a vital role in normal cellular processes such as signalling and membrane homeostasis, and are perturbed in cancer, lipid storage and muscle diseases. A new family of coat prote ....Structural basis for the assembly of caveolae. Caveolae are small invaginations of the plasma membrane and are a characteristic feature of eukaryotic cells. Described morphologically in the early 1950s their many important functions are only just beginning to be revealed. Caveolae are multifunctional organelles that play a vital role in normal cellular processes such as signalling and membrane homeostasis, and are perturbed in cancer, lipid storage and muscle diseases. A new family of coat proteins called cavins have recently been discovered. Cavins are essential for the formation of caveolae, and this project seeks to understand how these multiprotein complexes are assembled at the membrane interface and control caveola function at the molecular level.Read moreRead less