Subcellular architecture

Institution: Centro de Investigación en Nanomateriales y Nanotecnología (CINN)

Members (researchers): Jose-Jesus Fernandez

Home page: https://tiny.cc/neuroarch
Contact email: JJ.Fernandez@csic.es

Tools: Tomo3DEM

Service Units: Electron Microscopy Facility at CINN

Our research interest is mainly focused on the study of the subcellular architecture and exploration of the structural alterations under pathological conditions in neurodegenerative diseases, with particular focus on Huntington’s Disease. Our working hypothesis is that the maintance of the subcellular architecture is of paramount importance for the cellular homeostasis and that the analysis of such alterations may contribute to gain insights into the pathophysiological basis of diseases, to serve as a biomarker of disease progression and effects of therapeutic treatments and also to enable the identification of new therapeutic targets. In our work we develop and apply advanced preparation protocols based on cryo-fixation that ensure optimal structural preservation of samples from post-mortem brain tissue and peripheral tissues (muscle, blood), taken from animal models and patients. And we then use state-of-the-art 3D imaging and nanotomography technologies, namely (cryo-) electron tomography and (cryo-)FIB/SEM (focused ion beam scanning electron microscopy), and develop and apply advanced image processing methods to conduct the structural analysis.

Research topics:

Applications of Computational Biology, Clinical data, Computational Methods, Computational Techniques, Data Analysis, Data Visualization, Deep Learning in Biology, High-performance Computing, Image analysis, Machine Learning in Biology, Model organisms, Parallel Computing


Publications

Li, S., Fernandez, J. J., Ruehle, M. D., Howard-Till, R. A., Fabritius, A., Pearson, C. G., Agard, D. A., & Winey, M. E. (2025). The structure of basal body inner junctions from Tetrahymena revealed by electron cryo-tomography. The EMBO journal, 44(7), 1975–2001. https://doi.org/10.1038/s44318-025-00392-6

Martin-Solana, E., Casado-Zueras, L., Torres, T. E., Goya, G. F., Fernandez-Fernandez, M. R., & Fernandez, J. J. (2024). Disruption of the mitochondrial network in a mouse model of Huntington's disease visualized by in-tissue multiscale 3D electron microscopy. Acta neuropathologica communications, 12(1), 88. https://doi.org/10.1186/s40478-024-01802-2

Martinez-Sanchez, A., Garcia, I., Asano, S., Lucic, V., & Fernandez, J. J. (2014). Robust membrane detection based on tensor voting for electron tomography. Journal of structural biology, 186(1), 49–61. https://doi.org/10.1016/j.jsb.2014.02.015

Agulleiro, J. I., & Fernandez, J. J. (2011). Fast tomographic reconstruction on multicore computers. Bioinformatics (Oxford, England), 27(4), 582–583. https://doi.org/10.1093/bioinformatics/btq692