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Job Vacancy: Post Doctoral Research Assistant
in Electron Tomography - available now
We are looking for a highly motivated structural biologist to join our research group studying the fine structure of myosin binding protein C in cardiac muscle and how it is affected by mutations. The sample preparation will involve rapid freezing/freeze substitution for thin section electron microscopy. Electron tomography and sub-volume averaging will be used to determine the mean structures, essentially following the procedures in our recent paper (Luther et al, 2011, PNAS, 108:11423). Myosin binding protein C (MyBP-C) is a modular 135 kD protein in striated muscle located at regular intervals along each myosin filament and interacts with actin filaments and myosin S2. There is great interest in the cardiac isoform as mutations in the corresponding gene lead to heart disease, hypertrophic cardiomyopathy characterised by thickened heart walls. The post is funded for 5 years starting from February 2012 by a British Heart Foundation award. Applicants should have a PhD in a Biological or Physical Science subject and should be highly numerate. Experience in electron microscopy and electron tomography of sectioned biological samples and computing with linux is highly desirable The project offers the opportunity to work within a well-funded, world class 5* (RAE) department based at Imperial’s South Kensington Campus. The electron microscopes to be used for this project include a 200 KV FEI FEG em. Application form and details available here. For additional details please contact Dr. Pradeep Luther (p.luther@imperial.ac.uk). 5 Dec 2011: Oday defends his PhD thesis. Update 23 jan 2012: corrections approved!!
Oday submitted an excellent thesis on "Unravelling the 3D structure of vertebrate muscle M-band". Here he is relaxing after his ordeal. He had two wonderful examiners, Professor Peter Knight from Leeds University and Professor Erhard Hohenester from Imperial. From left: Lata, Pradeep, Oday, Rui.
The day after Oday's viva. Celebrating Oday's success, Christmas Dinner and Pradeep's BHF Programme grant award. It was a fun evening. First we enjoyed karaoke at Queen's Skate centre in Queensway, Bayswater Road. We had some great singers - Hannah, Kaiying and Anu. Others were entertaining nevertheless! This was followed by a sumptuous Chinese meal. From left, Sahir, Kaiying, Oday, Essa, Lata, Tom, Anu, Hannah, Pradeep.
17 Nov 2011: Pradeep awarded 5 year Programme Grant from the British Heart Foundation! We are recruiting a postdoc to work on this project. Expertise required: Electron microscopy and tomography, sample preparation using rapid freezing methods, ultramicrotomy. See top of page. 16 Nov 2011 Anupama wins 2nd Prize at Cryomicroscopy Group Meeting in Nottingham
Anu receiving 2nd Prize for the Freeze Frames Competition from Paul Verkade at the Cryomicroscopy Group Annual Meeting in Nottingham University on 16 November 2011. This consisted of presentation of the entrant's research in 90 seconds with just 2 slides. The title of Anu's presentation was "Electron tomography analysis of Myosin binding protein-C"
New paper: Govindan, S., McElligott, A., Muthusamy, S., Nair, N., Barefield, D., Martin, J. L., Gongora, E., Greis, K. D., Luther, P. K., Winegrad, S., Henderson, K. K., Sadayappan, S. (2011) Cardiac myosin binding protein-C: a new diagnostic role for myocardial infarction. J. Mol Cell Card Press coverage New paper: Luther, P.K., H. Winkler, K. Taylor, M.E. Zoghbi, R. Craig, R. Padron, J.M. Squire, and J. Liu. 2011. Direct visualization of
myosin-binding protein C bridging myosin and actin filaments in intact
muscle. Proc Natl Acad Sci U S A 108(28): 11423-11428. (PubMed) Abstract: Myosin-binding protein C (MyBP-C) is a thick filament protein playing an essential role in muscle contraction, and MyBP-C mutations cause heart and skeletal muscle disease in millions worldwide. Despite its discovery 40 y ago, the mechanism of MyBP-C function remains unknown. In vitro studies suggest that MyBP-C could regulate contraction in a unique way-by bridging thick and thin filaments-but there has been no evidence for this in vivo. Here we use electron tomography of exceptionally well preserved muscle to demonstrate that MyBP-C does indeed bind to actin in intact muscle. This binding implies a physical mechanism for communicating the relative sliding between thick and thin filaments that does not involve myosin and which could modulate the contractile process. Our "Press Release" - the story behind the research.
The tomogram displayed at two different densities: high density to show myosin crowns (crossbridges) and low density to show MyBP-C. The rods drawn in depict actin filaments. As the averaging was done relative to myosin filament centre, the density due to actin filament was suppressed. Quality of the Sample Preservation
Overlay of X-ray diffraction pattern in red of relaxed frog sartorius muscle (Huxley & Brown, 1967, with permission of Dr Huxley) and averaged Fourier transform in green of several electron micrographs of the fast-frozen/freeze-substituted muscle. There is excellent agreement between the two patterns, confirming the exquisite preservation of the sample used for the tomography. An electron micrograph of the sample, prepared by rapid-freezing/freeze-substitution is shown here. +++++++++++++++++++++++++++++++++++++++++++++++++++++++ Visit by 6th Formers, 1-2 August 2011
Work placement for 6th formers, Bethan, Shivani and Sneha, to experience the research of the Electron Tomography lab. They were shown section preparation, staining and photography for light microscopy followed by electron microscopy of normal and diseased skeletal muscle. From left, PKL, Sneha Verma, Bethan Williams, Shivani Aggarwal, Anupama Vydyanath, Hannah Somani. +++++++++++++++++++++++++++++++++++++++++++++++++++++++++ Exam results, 15 July 2011 Congratulations to Hannah Somani for achieving 2:1 BSc Hon in Biology. Hannah did an excellent final year project on electron tomography of the Z-band. She is now working over the summer in our lab to continue her project. Thanks, Hannah! +++++++++++++++++++++++++++++++++++++++++++++++++++++++ Molecular Medicine picnic at Hyde Park, 1 July 2011
Oday receiving the frisbee thrown by James
Anu watching Oday texting on his Blackberry
Valentina catching a frisbee with ease, watched over by Peter
MM members enjoying beer in the sunshine
Luck: While at the picnic in Kensington Gardens, I spotted the great man himself, David Hockney at work with his iPad in the new Serpentine Gallery Pavilion (designed by Peter Zumthor - must visit it properly soon). +++++++++++++++++++++++++++++++++++++++++++++++++++++++++ Exam results, 30 June 2011 Congratulations to Eliza Selley and James Geraets for achieving First Class Honours in their MSci Physics finals. They both did an excellent MSci project on electron tomography of rigor muscle. We look forward to having James in the lab for a UROP project over the summer before he embarks on his PhD in York University. +++++++++++++++++++++++++++++++++++++++++++++++++++++++++ Pradeep joins the BHF team at Imperial College on the London to Brighton Bike Ride - 19 June 2011 This was a meticulously organised event by the British Heart Foundation which saw about 30,000 riders zooming or puffing their way to Brighton along less-used beautiful roads. Many thanks to my sponsors - their generosity helped me to raise nearly £400 including giftaid. See my Sponsorship page here (now closed). See the BHF website for the ride here.
The Imperial team at our 7.30 am start in Clapham Common. Pictured, from left: Pradeep, Tony, Nicholas, Louisa, Jeroen, Rob, Eugene, Yean, Mariea.
The team at one of the early rest stops (when I was still keeping up with them!)
PKL photographed by Eugene - well done Eugene - he was cycling past me and shooting!
Relaxing after the Killer Hill - just after Ditchling village, getting ready for the easy ride into Brighton. There were several hills on the ride. I quickly realised there is no shame in getting off and walking - while I was being passed by very fit people, many much older than me.
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