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MRC Toxicology Unit

 

The EM & ultrastructural pathology group provides three-dimensional EM analysis for the Unit programs and external collaborative projects. Our “Nano-toxicology” is able to study a whole range of tissues and cells from the mouse brain to the signalling receptor-complexes involved in the response to toxins. Correlational 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 affected by toxins or drugs for mesothelioma in immune-oncology and neurogenerative diseases as well.

 

The techniques available include:

1) Serial-block face (SBF)-SEM for large-volume tissues and cells

2) TEM Tomography for cellular organelles

3) Single particle analysis for purified protein-complexes

4) CEMOVIS (Cryo-Electron Microscopy of Vitreous Sections)

5) Deep-etch, or freeze-fracture EM for plasma membrane (Membrane skeleton, Clathrin-coats, Caveolae) and other compartments

6) High-pressure freezing and freeze-substitution

7) CLEM (Correlation Light and Electron Microscopy)

8) Image processing with machine learning

 

The group is providing a training in image processing for the University students and researchers, which purpose is fine 3D-reconstruction and segmentation through the AMIRA, (the Relion and our originals).

 

Selected Publications

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. Mechanism of crosstalk between the LSD1 demethylase and HDAC1 deacetylase in the CoREST complex. Cell Rep. 2020 Feb 25;30(8):2699-2711.e8. doi: 10.1016/j.celrep.2020.01.091.

Kim H, Nobeyama T, Honda S, Yasuda K, Morone N, Murakami T. Membrane fusogenic high-density lipoprotein nanoparticles. Biochim Biophys Acta Biomembr. 2019 Oct 1;1861(10):183008. doi: 10.1016/j.bbamem.2019.06.007.

Robinson SW, Bourgognon JM, Spiers JG, Breda C, Campesan S, Butcher A, Mallucci GR, Dinsdale D, Morone N, Mistry R, Smith TM, Guerra-Martin M, Challiss RAJ, Giorgini F, Steinert JR. Nitric oxide-mediated posttranslational modifications control neurotransmitter release by modulating complexin farnesylation and enhancing its clamping ability. PLoS Biol. (2018) 16(4):e2003611. doi: 10.1371/journal.pbio.2003611.

Nishimura T, Morone N, Suetsugu S. Membrane re-modelling by BAR domain superfamily proteins via molecular and non-molecular factors. Biochem Soc Trans. (2018) 46(2):379-389. doi: 10.1042/BST20170322.

Sone M, Morone N, Nakamura T, Tanaka A, Okita K, Woltjen K, Nakagawa M, Heuser JE, Yamada Y, Yamanaka S, Yamamoto T. Hybrid Cellular Metabolism Coordinated by Zic3 and Esrrb Synergistically Enhances Induction of Naive Pluripotency. Cell Metab. (2017) 25(5):1103-1117. doi: 10.1016/j.cmet.2017.04.017.

Agostini M, Romeo F, Inoue S, Niklison-Chirou MV, Elia AJ, Dinsdale D, Morone N, Knight RA, Mak TW, Melino G. Metabolic reprogramming during neuronal differentiation. Cell Death Differ. 2016 Apr 8. doi: 10.1038/cdd.2016.36.

Fujiwara TK, Iwasawa K, Kalay Z, Tsunoyama TA, Watanabe Y, Umemura YM, Murakoshi H, Suzuki KG, Nemoto YL, Morone N, Kusumi A. Confined diffusion of transmembrane proteins and lipids induced by the same actin meshwork lining the plasma membrane. Mol Biol Cell. 2016 Apr 1;27(7):1101-19. doi: 10.1091/mbc.E15-04-0186.

Viticchiè G, Agostini M, Lena AM, Mancini M, Zhou H, Zolla L, Dinsdale D, Saintigny G, Melino G, Candi E. p63 supports aerobic respiration through hexokinase II. Proc Natl Acad Sci U S A. 2015 Sep 15;112(37):11577-82. doi: 10.1073/pnas.1508871112.

Peretti D, Bastide A, Radford H, Verity N, Molloy C, Martin MG, Moreno JA, Steinert JR, Smith T, Dinsdale D, Willis AE, Mallucci GR. RBM3 mediates structural plasticity and protective effects of cooling in neurodegeneration. Nature. 2015 Feb 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. Enhancing nucleotide metabolism protects against mitochondrial dysfunction and neurodegeneration in a PINK1 model of Parkinson’s disease. Nat Cell Biol. 2014 Feb;16(2):157-66. doi: 10.1038/ncb2901.