Image2Pharma: Image processing in electron cryomicroscopy and its impact on the pharmaceutical industry

Javier Vargas Balbuena has a research career of more than ten years during which he has had the opportunity to work in various centres such as the Optics Department of the Complutense University of Madrid, the National Institute of Aerospace Technology, the Higher Polytechnic School of the San Pablo CEU University, or the National Centre for Biotechnology. He has completed two international stays at the Catholic University of Leuven and Leiden University. His main research focus is the development of new image and signal processing methods, which he has applied to various fields such as optical metrology, spatial optics, and structural biology. He obtained several grants and awards throughout his career, such as a FPU predoctoral fellowship, a post-doctoral “Juan de la Cierva” contract, and an EMBO grant. As a result of his research, he has published more than 77 scientific-technical publications and has participated in more than 15 research projects. ComFuturo Researcher (I edition) at the National Centre for Biotechnology of the CSIC, where he developed his project “Image processing in electron cryomicroscopy and its impact on the pharmaceutical industry“.

Project Summary

The field of Electronic Cryomicroscopy (EC) is currently undergoing a revolution in both hardware and software, which is allowing it to begin to analyse macromolecular structures at high resolution, being able to resolve details as fine as 3 Angstroms relatively routinely in the structure and with the horizon set on breaking this barrier. Additionally, EC has the potential to provide both functional and ligand interaction information by processing and analysing the structural and conformational heterogeneity present in microscopy images. Knowing the three-dimensional shape of a macromolecular structure at this level of detail, as well as its dynamics and interactions with ligands, will help pharmaceutical companies in a radical way in the design of new pharmaceuticals with therapeutic applications and will establish a strong and stable link between Structural Biology through electron cryomicroscopy and the pharmaceutical industry. This connection will enable the latter to significantly reduce the production costs and development times of new drugs through a significant increase in the available structural information. It will also allow a qualitative leap in the field of electronic microscopy through new, stable, and robust sources of funding. The establishment of this connection requires the development of new computational methods in electronic cryomicroscopy based on advanced image processing algorithms and statistical methods of data analysis. The objectives of the project are to design the necessary tools to break the 3 Å resolution barrier, develop new algorithms for heterogeneity analysis, and finally propose validation methods to determine the quality and reliability of the determined structures.


The field of electron cryomicroscopy is undergoing a revolution that has allowed us to start analysing macromolecular structures at very high resolution. Knowing the three-dimensional shape of a macromolecular structure at this level of detail, as well as its dynamics and interactions with ligands, will radically help pharmaceutical companies to design new drugs with therapeutic applications, significantly reducing production costs and development times.

Macromolecule reconstructed with cryo-EM with its fitted atomic structure

Scientific production derived from the ComFuturo Project

Scientific articles


  • J. Vargas; R. Melero; J. Gomez-Blanco; JM Carazo; COS Sorzano (2017). Quantitative analysis of 3D alignment quality: its impact on soft-validation, particle pruning and homogeneity analysis. SCIENTIFIC REPORTS. DOI: 10.1038/s41598-017-06526-z


  • D. Calles Garcia; M. Yang; N. Soya; R. Melero; M. Ménade; Y. Ito; J. Vargas; G.L. Lukacs; J.M. Kollman; G. Kozlov; K. Gehring (2017) Single-particle electron microscopy structure of UDPglucose: glycoprotein glucosyltransferase suggests a selectivity mechanism for misfolded proteins. JOURNAL OF BIOLOGICAL CHEMISTRY. DOI: 10.1074/jbc.M117.789495


  • J. Vargas; E. Franken; C.O.S Sorzano; J. Gomez-Blanco; R. Schoenmakers; A.J. Koster; J.M. Carazo (2016). Foil-hole and data image quality assessment in 3DEM: towards high-throughput image acquisition in the electron microscope. JOURNAL OF STRUCTURAL BIOLOGY. DOI: 10.1016/j.jsb.2016.10.006


  • J.L. Vilas; J. Navas; J. Gomez-Blanco; J.M de la Rosa-Trevín; R. Melero; I. Peschiera; I. Ferlengui; J. Cuenca; J.M. Carazo; J. Vargas, C.O.S Sorzano (2016). Fast and automatic identification of particles tilt pairs based on Delaunay triangulation. JOURNAL OF STRUCTURAL BIOLOGY. DOI: 10.1016/j.jsb.2016.10.007


  • C.O.S Sorzano; J. Vargas; J. Oton; V. Abrishami; J.M. de la Rosa-Trevín; J. Gomez-Blanco; J.L. Vilas; R. Marabini, J.M. Carazo (2016). A review of resolution measures and related aspects in 3D Electron Microscopy. PROGRESS IN BIOPHYSICS AND MOLECULAR BIOLOGY. DOI: 10.1016/j.pbiomolbio.2016.09.005


  • J. Vargas Balbuena; J. Otón Perez; R. Marabini Ruíz; J.M. Carazo García; C.O.S. Sorzano (2016). Particle alignment reliability in single particle electron cryomicroscopy. SCIENTIFIC REPORTS. DOI:10.1038/srep21626


  • J.M. de la Rosa Trevin; A. Quintana Pérez; L. del Caño; A. Zaldivar Peraza; I. Foche Pérez; J. Gutiérrez; J. Gómez Blanco; J. Burguet Castells; J. Cuenca Alba; V. Abrishami; J. Vargas Balbuena; J. Otón Perez; G. Sharov; J.L. Vilas Prieto; J. Navas Calvente; P. Conesa; M. Kazemi; R. Marabini Ruíz; C.O.S. Sorzano; J.M. Carazo García (2016). Scipion: a software framework toward integration, reproducibility, and validation in 3D Electron Microscopy. JOURNAL OF STRUCTURAL BIOLOGY. DOI: 10.1016/j.jsb.2016.04.010


  • C.O.S. Sorzano; A. Martín Ramos; F. Prieto; R. Melero del Rio; J. Martín Benito; S. Jonic; J. Navas Calvente; J. Vargas Balbuena; J. Otón Perez; V. Abrishami; J.M. de la Rosa Trevin; J. Gomez Blanco; J.L. Vilas Prieto; R. Marabini Ruíz; J.M. Carazo García (2016). Local analysis of strains and rotations for macromolecular electron microscopy maps (in press). JOURNAL OF STRUCTURAL BIOLOGY. DOI: 10.1016/j.jsb.2016.04.001


Works presented at conferences


  • J. VargasQuantitative analysis of 3D alignment in cryo-EM: soft-validation, particle pruning and homogeneity analysis. Canadian Microscopy & Cytometry Symposium 2017. Invited oral presentation. Montreal, Canada. 9/05/2017-12/05/2017


  • J. Vargas Balbuena; J.M. Carazo Garcia; C.O.S. Sorzano. Soft alignment validation in cryo-electron microscopy. Cryo-EM 3D Image Analysis Symposium 2016. Invited oral presentation. Tahoe, United States of America. 30/03/2016 – 02/04/2016


Invited scientific talks


  • Computational Challenges in high-resolution cryogenic electron microscopy (2016). Invited Speaker. Department of Anatomy and Cell Biology, McGill University, Montreal, Canada.


  • Breaking resolution barriers in cryo-EM: current state and computational challenges ahead (2017). Invited speaker. Department of Computer Science, Duke University, Durham, USA.