The EM & Ultrastructural Pathology facility provides three-dimensional EM analysis for the core MRC Toxicology Unit programmes and the external collaborative projects. Our “Nano-toxicology” approach enables the study of a whole range of tissues and cells from mouse brain to signalling receptor-complexes involved in the response to toxins. Correlative changes between structure and function can be examined in nanoscale by using Cryo-TEM, SBF-SEM, and CLEM techniques for an in-depth visualisation of areas adversely affected by toxins or drugs.
The designed EM techniques at MRC Toxicology Unit:
- Cryo-Single Particle Analysis (SPA) TEM for purified protein complexes
- Negative staining TEM for pre-screening before SPA
- Cryo-Electron Microscopy of Vitreous Sections (CEMOVIS)
- (Cryo-)TEM tomography for intracellular organelles
- Plunge freezing with Vitrobot
- Serial-Block Face (SBF)-SEM with 3View system for large volume tissue and cellular architectures
- Array tomography with standard SEM for intracellular organelles
- Image processing with machine learning modules
- High-pressure freezing and freeze-substitution
- Immune-gold labelling for protein subcellular localisation
- Correlation Light and transmission or scanning Electron Microscopy (CLEM)
- Deep-etch, or freeze fracture EM for plasma membranes, other membrane compartments and cytoskeletal organisation
- Conventional TEM for plastic ultra-sections
- Conventional SEM with gold sputtering
*Request for Research Collaboration: Please contact the Head of the Facility, Dr Nobu Morone in advance. The EM Facility is responsible for all levels of procedures for EM imaging and analysis support. This encompasses a complete service, including an initial meeting, which is essential for identification of the most effective EM solution, experimental designs, and time schedules.
EM Imaging Suite
JEOL JEM1400HC TEM - TVIPS TemCam-XF416
FEI Quanta 250FEG SEM
Gatan 3View System - OnPoint BSE Detector
Quorum GloQube Glow Discharge System, K950X Turbo Evaporator
Leica EM Artos3D, TRIM2, TP, KMR3
(Cryo-EM server for Relion and CryoSparc)
Cryo-EM Suite
FEI Talos F200C - FalconDED, Vitrobot
Gatan Cryo-Transfer Holder 626/914, Turbo Pumping Station
Fischione Advanced Tomography Holder (RT) 2020
Leica EM HPM100, AFS2/FSP
Leica EM FC7/UC7/Manipulator, CRION
JEOL JFDII
Imaging Tech
Workstation for Amira3D, EMAN2, Inspect3D/Argos
Facility staff
Selected Publications
Hardy RE, Chung I, Yu Y, Loh SHY, Morone N, Soleilhavoup C, Travaglio M, Serreli R, Panman L, Cain K, Hirst J, Martins LM, MacFarlane M, Pryde KR. (2023) The antipsychotic medications aripiprazole, brexpiprazole and cariprazine are off-target respiratory chain complex I inhibitors. Biol Direct. 18(1):43.
Grosso S, Marini A, Gyuraszova K, Voorde JV, Sfakianos A, Garland GD, Tenor AR, Mordue R, Chernova T, Morone N, Sereno M, Smith CP, Officer L, Farahmand P, Rooney C, Sumpton D, Das M, Teodósio A, Ficken C, Martin MG, Spriggs RV, Sun XM, Bushell M, Sansom OJ, Murphy D, MacFarlane M, Le Quesne JPC, Willis AE. (2021) The pathogenesis of mesothelioma is driven by a dysregulated translatome. Nat Commun. 12(1):4920.
Fox JL, Hughes MA, Meng X, Sarnowska NA, Powley IR, Jukes-Jones R, Dinsdale D, Ragan TJ, Fairall L, Schwabe JWR, Morone N, Cain K, MacFarlane M. (2021) Cryo-EM structural analysis of FADD:Caspase-8 complexes defines the catalytic dimer architecture for co-ordinated control of cell fate. Nat Commun. 12(1):819.
Buckley N, Panatta E, Morone N, Noguchi M, Scorrano L, Knight RA, Amelio I, Melino G. (2020) P73 C-terminus is dispensable for multiciliogenesis. Cell Cycle. 19(14):1833-1845.
Amelio I, Panatta E, Niklison-Chirou MV, Steinert JR, Agostini M, Morone N, Knight RA, Melino G. (2020) The C terminus of p73 is essential for hippocampal development. Proc Natl Acad Sci USA. 117(27):15694-15701.
Song Y, Dagil L, Fairall L, Robertson N, Wu M, Ragan TJ, Savva CG, Saleh A, Morone N, Kunze MBA, Jamieson AG, Cole PA, Hansen DF, Schwabe JWR. (2020) Mechanism of crosstalk between the LSD1 demethylase and HDAC1 deacetylase in the CoREST complex. Cell Rep. 30(8):2699-2711.e8.
Morone N, Usukura E, Narita A, Usukura J. (2020) Improved unroofing protocols for cryo-electron microscopy, atomic force microscopy and freeze-etching electron microscopy and the associated mechanisms. Microscopy (Oxford). 69(6):350-359. doi: 10.1093/jmicro/dfaa028.
Peretti D, Bastide A, Radford H, Verity N, Molloy C, Martin MG, Moreno JA, Steinert JR, Smith T, Dinsdale D, Willis AE, Mallucci GR. (2015) RBM3 mediates structural plasticity and protective effects of cooling in neurodegeneration. Nature. 12;518(7538):236-9. doi: 10.1038/nature14142.
Tufi R, Gandhi S, de Castro IP, Lehmann S, Angelova PR, Dinsdale D, Deas E, Plun-Favreau H, Nicotera P, Abramov AY, Willis AE, Mallucci GR, Loh SH, Martins LM. (2014) Enhancing nucleotide metabolism protects against mitochondrial dysfunction and neurodegeneration in a PINK1 model of Parkinson's disease. Nat Cell Biol. 16(2):157-66. doi: 10.1038/ncb2901.
Sinha B, Köster D, Ruez R, Gonnord P, Bastiani M, Abankwa D, Stan RV, Butler-Browne G, Vedie B, Johannes L, Morone N, Parton RG, Raposo G, Sens P, Lamaze C, Nassoy P. (2011) Cells respond to mechanical stress by rapid disassembly of caveolae. Cell. 144(3):402-13.