Biological complexes in action, in vitro and in silico (Exploiting Big-Data in Cryo-EM)

• Grant number: 20/06062-1
• Support Opportunities: Research Projects - Thematic Grants
• Start date: April 01, 2022
• End date: March 31, 2027
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Marin Gerard van Heel
• Grantee: Marin Gerard van Heel
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Campinas , SP, Brazil
• Pesquisadores principais: Rodrigo Villares Portugal
• Associated researchers: Andre Luis Berteli Ambrosio ; Angelo Luiz Gobbi ; Daniel Guerra Giraldez ; Gabriela Dias Noske ; Pedro Ismael da Silva Junior ; Shaker Chuck Farah
• Associated scholarship(s): 25/09969-1 - Structural studies of various hemocyanins in different conformations/functional states, BP.PD; 25/02851-5 - Local Fourier Shell Information (FSI) for assessing Biological 3D structures., BP.IC; 24/03118-7 - Infrastructure development for time-resolved cryo-EM, BP.PD; + associated scholarships 24/03080-0 - Integration of Single Particle Analysis methods and software in the cryo-EM production pipeline, BP.TT; 24/03426-3 - Optimizing global and local data processing after data collection for single particle cryo-EM, BP.PD; 23/04847-0 - Development of a Cryo-EM pipeline for ligand discovery for SARS-CoV-2 Spike protein, BP.DD; 20/01156-8 - Local properties of biological complexes studied by local cryo-EM metrics, BP.PD - associated scholarships

Abstract

Biological molecules in solution are the basis of life. Vitrified solutions of biological complexes can now be imaged directly in a cryogenic electron microscope (cryo-EM), and provide a window into the functioning of our bio-molecular machinery. However, the molecules only tolerate a very low electron exposure dose and the raw data are thus necessarily very noisy. Huge data sets (~Terabytes) have to be collected in order to harvest enough information for answering subtle biological questions. Extracting intrinsic information from very noisy data may require solving some of the largest eigenvector-eigenvalue problems known to science. Decades of methodological advances led to the current cryo-EM "resolution revolution". Especially important was the recent advent of efficient "direct electron detectors" leading to an avalanche of new structures (2017 Wiley Award; 2017 Nobel Prize in Chemistry). The latest generation of cryo-EMs have recently been installed at LNNano/CNPEM. With this grant we want to achieve a critical mass of researchers in the centre to catapult Brazil to the forefront of the international cryo-EM community. We will create efficient data-collection and data-processing pipelines for the Brazilian community. Those pipelines will include advanced instrumentation methodology (sample preparation, cameras, data quality control, full dataset CTF correction etc.) as well as structural biology methodology (4D analysis, local refinements, coordinates fitting, revealing glycosylation, etc.). The new methodology will help optimise the output of our expensive instrumentation. We must train a new generation of specialists for which there is a huge demand (and to counter continuous brain-drain). All researchers will also solve cryo-EM structures, such as viral pathogens like Zika and alpha viruses, relevant to Brazil. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE NIZ, MARIANA; GARCIA, RODRIGO ESCOBEDO; RAMIREZ, CELINA TERAN; PAKOWSKI, YSA; ABONZA, YURINEY; BIALY, NIKKI; ORR, VANESSA L.; OLIVERA, ANDRES; ABONZA, VICTOR; ALLEVA, KARINA; et al. Building momentum through networks: Bioimaging across the Americas. JOURNAL OF MICROSCOPY, v. 294, n. 3, p. 20-pg., 2024-05-15. (20/06062-1, 22/05088-2)

PERALTA-MARTINEZ, RAMON; VISENTIN, ARACELI; SALGUEIRO, MARIANO; BORKOSKY, SILVIA SUSANA; ALEIXO, MARIANA ARAUJO AJALLA; PORTUGAL, RODRIGO VILLARES; SANCHEZ, IGNACIO ENRIQUE; PRAT-GAY, GONZALO. Protein-RNA condensation kinetics via filamentous nanoclusters. Protein Science, v. 34, n. 6, p. 14-pg., 2025-06-01. (20/06062-1, 22/05088-2)

ADAMOSKI, DOUGLAS; DIAS, MARILIA MEIRA; QUESNAY, JOSE EDWIN NECIOSUP; YANG, ZHENGYI; ZAGORIY, IEVGENIIA; STEYER, ANNA M.; RODRIGUES, CAMILA TANIMOTO; DA SILVA BASTOS, ALLINY CRISTINY; DA SILVA, BIANCA NOVAES; COSTA, RENNA KAROLINE ELOI; et al. Molecular mechanism of glutaminase activation through filamentation and the role of filaments in mitophagy protection. NATURE STRUCTURAL & MOLECULAR BIOLOGY, v. 30, n. 12, p. 33-pg., 2023-10-19. (17/15340-2, 17/11766-5, 21/01504-9, 21/03933-4, 14/12663-7, 19/16351-3, 21/13736-1, 16/09077-4, 14/20673-2, 20/06062-1, 13/07600-3)