National Heart & Lung Institute (NHLI)

Molecular Medicine

These images were obtained by Dr Valentina Caorsi using the FILM facility, and were published in the FILM calendar 2010. 

They represent different views of skeletal muscle obtained with a Leica SP5 upright microscope. One image was obtained by Second Harmonic Generation and using two-photon excitation at 850 nm to alter the fibre shape. The other images were obtained by using fluorescent labels on actin, on the myosin essential light chain or on myosin's reactive thiol SH1. The 'square' was obtained by photobleaching, to investigate the existence of FRET between two of the labels, thus demonstrating that their labelling sites are less than 10 nm apart.

  • Psoas skeletal muscle fibre labelled with Alexa594 on SH1
  • Psoas skeletal muscle fibre labelled with Alexa594 on SH1
  • Psoas skeletal muscle fibre
  • Psoas skeletal muscle fibre labelled with Alexa488 on the essential light chain and Rhodamine Phalloidin on Actin

The Section of Molecular Medicine (MM) was created in August 2007, as a result of the merging of the sections of Molecular and Cellular Medicine and Biological Nanoscience. The Section is housed in the Sir Alexander Fleming Building on the South Kensington Campus of Imperial College. Most laboratories are found on the 2nd floor. MM regroups scientists with interests in fundamental aspects of cell and molecular biology, enhanced by expertise in physiology, biophysics, spectroscopy, single molecule imaging and state-of-the-art microscopies. The work extends research in the basic sciences at the National Heart and Lung Institute.

Current Principal Investigators in the Section include:

Research in the section is principally funded from programme and project grants from Research Councils (MRC, BBSRC) and charities (Wellcome Trust, British Heart Foundation and others).

Molecular Medicine Section - July 2011

Molecular Medicine Section - July 2011

 

Over sixty staff and students currently work in the Section, including nine heads of laboratories, over 20 PhD students, over 20 Postdocs and researchers, two technicians and a number of MRes students, visitors and honorary researchers. The Section Administrator is Catherine Enright (c.enright@imperial.ac.uk; Desk 123, 2nd Floor, Sir Alexander Fleming Building)

Selected publications

Barclay, CJ, Woledge, RC & Curtin, NA (2010). Inferring crossbridge properties from skeletal muscle energetics. Progress in Biophysics and Molecular Biology 102: 53-71.

Chang, SC, Mulloy, B, Magee, AI and Couchman, JR (2011). Two distinct sites in sonic hedgehog combine for heparan sulfate interactions and cell signaling functions. J. Biol. Chem. 286: 44391-402.

Carroll B, Mohd-Naim N, Maximiano F, Frasa MA, McCormack J, Finelli M, Thoresen SB, Perdios L, Daigaku R, Francis RE, Futter C, Dikic I, Braga VM (2013). The TBC/RabGAP Armus Coordinates Rac1 and Rab7 Functions during Autophagy. Dev. Cell [Epub ahead of print].

Lenn T, Gkekas C, Bernard L, Engl C, Jovanovic G, Buck M, Ying LM (2011). Measuring the Stoichiometry of Functional PspA Complexes in Living Bacterial Cells by Single Molecule Photobleaching, Chem. Comm. 47: 400-402.

Lewis A; Riddoch-Contreras J; Natanek SA; Donaldson A; Man WD; Moxham J; Hopkinson NS; Polkey MI; Kemp PR (2012). Downregulation of the serum response factor/miR-1 axis in the quadriceps of patients with COPD. Thorax. 67: 26-34. 

Luther, PK, Winkler, H, et al (2011). Direct visualization of myosin-binding protein C bridging myosin and actin filaments in intact muscle. Proc Natl Acad Sci USA 108(28): 11423-11428

Natanek SA, Gosker HR, Slot IGMS, Marsh GS, Hopkinson NS, Man WD-C, Moxham J, Kemp PR, Schols AMWJ and Polkey M I (2012). Pathways associated with reduced quadriceps oxidative fibres and endurance in COPD. Eur Respir J [Epub ahead of print].

Singh RK, Liao W, Tracey-White D, Recchi C, Tolmachova T, Rankin SM, Hume AN, Seabra MC (2012). Rab27a-mediated protease release regulates neutrophil recruitment by allowing uropod detachment. J. Cell Sci. 125: 1652-6

Solomon A, Smyth E, Mitha N, Pitchford S, Vydyanath A, Luther PK, Thorley AJ, Tetley TD and Emerson M (2013). Induction of platelet aggregation after direct physical interaction with diesel exhaust particles.  J. Thromb. Haemost. 11: 325-34.

West TG, Hild G, Siththanandan VB, Webb MR, Corrie JET, Ferenczi MA (2009).  The time-course and strain dependence of ADP release during contraction of permeabilized muscle fibers. Biophysical Journal 96: 3281-3294.

Xu, H, Bihan, D, Chang, F, Huang, PH, Farndale, RW & Leitinger B (2012). Discoidin domain receptors promote α1β1- and α2β1-integrin mediated cell adhesion to collagen by enhancing integrin activation. PLoS ONE 7: e52209.

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FILM
FILM, the Facility for Imaging by Light Microscopy, is also hosted in the section.  FILM provides two wide-field and six confocal microscopes, with a variety of configurations, for achieving the highest quality images. We have upright and inverted microscopes, FLIM and FRET for a wide range of fluorophores, environmental chambers for live cell imaging, imaging software and data storage. FILM is run by Dr Martin Spitaler and a full time assistant.
Fluorescence Life Time Image

Fluorescence Life Time Image

Fluorescence Life Time Image of a mammalian muscle fibre labelled with a fluorescent nucleotide analogue. The striations are characteristic of skeletal muscle and reveal the sarcomeres, the repeating units containing the arrays of protein filaments responsible for muscle contraction. The nucleotide binds to the active site of myosin and the life-time reveals the ability of the myosin to interact with actin.
(DI García, PMP Lanigan, MR Webb, TG West, J Requejo Isidro, E Auksorius, CW Dunsby, MAA Neil, PMW French, MA Ferenczi (2007) Fluorescence lifetime imaging to detect actomyosin states in mammalian muscle sarcomeres. Biophysical Journal 93: 2091-2101.)