Electron Tomography of Muscle Sarcomere

Laboratory of Pradeep Luther, PhD

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September 2015: Group attends European Muscle Conference, Warsaw

At the European Muscle Conference in Warsaw, September 2015. Stefan Galler, Masataki Kawai, Zhan Yin, Pradeep Luther

At the European Muscle Conference in Warsaw, September 2015. Imperial College London participants: Pradeep Luther, Andrew Messer, Natalia Smoktunowicz, Maria Papadaki, Steve Marston.

At the European Muscle Conference in Warsaw, September 2015. From left: x,x,Roser Farre-Garros, x,x,Michele Chiappi, Maria Papadaki, Natalia Smoktunowicz,

 

20 September 2014: Sam Lacey wins Best Poster Award at European Muscle Conference, Salzburg

Congratulations to Sam Lacey for winning the Best Poster Award at the 43rd European Muscle Conference, held in Salzburg.  In this picture are (from left) supervisor Pradeep Luther, EMC conference organiser, Dr Stefan Galler, Sam Lacey and Steve Hunter.

25 September 2013: Steve Hunter wins Young Investigator Prize at European Muscle Conference, Amsterdam.

Congratulations to Steve for winning the Young Investigator Prize at the 42nd European Muscle Conference, held in Amsterdam.  He is seen here with supervisor Pradeep Luther (left) and Professor Jolanda van der Velden, organiser of the conference.

 

16 June 2013: Pradeep rides in the BHF London to Brighton bike ride

Pradeep participated in the BHF sponsored London to Brighton bike ride.  For more details please visit my sponsorship page:

 http://uk.virginmoneygiving.com/PradeepLuther

November 2013: London to Brighton Bike Ride sponsorship

Thank you everyone for your very generous support of my ride and the British Heart Foundation.

25 March 2013: Lab outing to Westend to see "Singing in the Rain"

Lab outing to the Westend to see thousands of gallons of water raining on-stage!  It was a super performance.  From left: Steve Hunter, Jonathan Lambert, Alice Mitchell and Mozhgon Jeddi.  Unfortunately some group members, Iratxe Toree, Anna Rammou and Amina Yonis could not join us.

18 March 2013: Mozhgon Jeddi delivering her talk at Alpbach

Mozhgon presenting her talk at Alpbach (ski-resort in the Alps!).  Listening to her intently in the foreground is none other than our main man, Professor Hugh Huxley.

23 August 2012: Lab visit to Queens Tower

On a beautiful summer day, we climbed to the top of Queen's Tower - you can see Albert Hall below us in the backgound.  From left, Steve Hunter, summer UROP project; Pradeep Luther, Anu Vydyanath, Ivan Imat-Roldan and Iratxe Torre.

 

5 Dec 2011: Oday defends his PhD thesis.  Update May 2012, Oday Graduates

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.

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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.

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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!

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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).

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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.

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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.