Structure and function studies of isolated Z-discs from muscle
The Z-disc is the anchoring structure for the ends of thin (actin) filaments and transmits contractile force between adjacent muscle sarcomeres. The primary linkages between thin filament ends of opposite polarity here are Z-bridges composed of-actinin. In addition to have this purely mechanical function, the Z-disc is now known to contain ~40 different proteins and to have several other functions, particularly stress sensing into nuclear and proteolytic signalling pathways involving muscle growth and degradation. Because it has so far only been studied in the electron microscope in thin sections, the structure of the Z-disc is known only in outline, to a resolution of 4-5 nm, whereas ~2 nm resolution is required to recognise protein shapes and accurately dock crystal structures. There are reports of the preparation of isolated Z-discs from both invertebrate and vertebrate muscle 50 years ago, but such preparations have not been subjected to modern electron microscopy methods, such as cryo-EM or tomography. Isolated Z-discs are a valuable specimen for EM studies because they are a naturally thin and do not have to be cut into thin sections, which causes damage and loss of resolution. To obtain 3D models with improved resolution, this project will study isolated Z-discs from both invertebrate and vertebrate muscle, including cardiac. Isolated Z-discs are also valuable for compositional studies, such as monitoring gain and loss of components that are transient in vivo. In addition to its fundamental importance in biology, this project will provide an excellent training in modern electron microscopy (cryo-tomography, image processing) as well as a wide variety of biochemical methods.
Further details from Prof John Trinick ([email protected]
See also http://www.fbs.leeds.ac.uk/staff/profile.php?un=chbjat
Competitive schemes are open in the Faculty of Biological Sciences at Leeds University, including BBSRC DTC and Wellcome Trust programmes.
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