Integrative Cryo-Imaging

Group leader
Sergi Padilla
Address

Biofisika Institute (CSIC, EHU)
Science Park of the EHU
Barrio Sarriena s/n. 48940 Leioa, Bizkaia (Spain)

Research goal

The Integrative Cryo-Imaging Lab develops next-generation imaging technologies to connect molecular structure with biological function across scales. A central focus is the development and quantitative characterization of fluorescent probes and photonic measurements under cryogenic conditions, including detailed analysis of fluorophore behavior in cryo environments. By integrating advanced optical microscopy, cryogenic photonics, and cryo-electron tomography, the lab aims to establish a unified imaging pipeline that goes beyond traditional CLEM, enabling direct integration of structural, photonic, and functional information. To achieve this, we develop and combine single-molecule microscopy, fluorescence lifetime imaging, spectral and functional imaging, and super-resolution approaches such as DNA-PAINT, alongside AI-guided design of fluorescent proteins and biosensors. These technologies are applied to a range of biological questions, with a particular focus on viral entry and membrane fusion. As an example, we study Class I viral fusion proteins, including HIV-1 Env, Ebola GP, Nipah F, and coronavirus Spike. By integrating imaging modalities across single molecules, viral particles, cells, and tissues, the lab seeks to uncover the biophysical principles governing membrane fusion and other dynamic biological processes.

Group members
Ikerbasque Research Professor
Publications

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Starling T, Carlon-Andres I, Iliopoulou M, Kraemer B, Loidolt-Krueger M, Williamson DJ, Padilla-Parra S

Multicolor lifetime imaging and its application to HIV-1 uptake
Nat Commun. 2023 Aug 17;14(1):4994
doi: 10.1038/s41467-023-40731-x

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Padilla-Parra S

Next-generation single virus tracking
Nat Methods. 2022 Dec;19(12):1524-1525
doi: 10.1038/s41592-022-01670-5

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Tebo AG, Moeyaert B, Thauvin M, Carlon-Andres I, Böken D, Volovitch M, Padilla-Parra S, Dedecker P, Vriz S, Gautier A

Orthogonal fluorescent chemogenetic reporters for multicolor imaging
Nat Chem Biol. 2021 Jan;17(1):30-38
doi: 10.1038/s41589-020-0611-0

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Anzilotti C, Swan DJ, Boisson B, Deobagkar-Lele M, Oliveira C, Chabosseau P, Engelhardt KR, Xu X, Chen R, Alvarez L, Berlinguer-Palmini R, Bull KR, Cawthorne E, Cribbs AP, Crockford TL, Dang TS, Fearn A, Fenech EJ, de Jong SJ, Lagerholm BC, Ma CS, Sims D, van den Berg B, Xu Y, Cant AJ, Kleiner G, Leahy TR, de la Morena MT, Puck JM, Shapiro RS, van der Burg M, Chapman JR, Christianson JC, Davies B, McGrath JA, Przyborski S, Santibanez Koref M, Tangye SG, Werner A, Rutter GA, Padilla-Parra S, Casanova JL, Cornall RJ, Conley ME, Hambleton S

An essential role for the Zn2+ transporter ZIP7 in B cell development.
Nat Immunol. 2019 Mar;20(3):350-361
doi: 10.1038/s41590-018-0295-8

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Iliopoulou M, Nolan R, Alvarez L, Watanabe Y, Coomer CA, Jakobsdottir GM, Bowden TA, Padilla-Parra S

A dynamic three-step mechanism drives the HIV-1 pre-fusion reaction
Nat Struct Mol Biol. 2018 Sep;25(9):814-822
doi: 10.1038/s41594-018-0113-x

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Kong Y, Janssen BJ, Malinauskas T, Vangoor VR, Coles CH, Kaufmann R, Ni T, Gilbert RJ, Padilla-Parra S, Pasterkamp RJ, Jones EY

Structural Basis for Plexin Activation and Regulation
Neuron. 2016 Aug 3;91(3):548-60
doi: 10.1016/j.neuron.2016.06.018

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Zhao Y, Ren J, Harlos K, Jones DM, Zeltina A, Bowden TA, Padilla-Parra S, Fry EE, Stuart DI

Toremifene interacts with and destabilizes the Ebola virus glycoprotein
Nature. 2016 Jul 7;535(7610):169-172
doi: 10.1038/nature18615

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Healey EG, Bishop B, Elegheert J, Bell CH, Padilla-Parra S, Siebold C

Repulsive guidance molecule is a structural bridge between neogenin and bone morphogenetic protein
Nat Struct Mol Biol. 2015 Jun;22(6):458-65
doi: 10.1038/nsmb.3016

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Zhao Y, Ren J, Padilla-Parra S, Fry EE, Stuart DI

Lysosome sorting of β-glucocerebrosidase by LIMP-2 is targeted by the mannose 6-phosphate receptor
Nat Commun. 2014 Jul 14;5:4321
doi: 10.1038/ncomms5321