Ries Lab

We are studying nanoscale multi-protein machineries in their functional cellular context, and elucidates their dynamic structural organisation using tailor-made superresolution microscopy technologies.

Research in the Ries Lab

Previous and current research

Like nanoscopic machines, protein complexes and assemblies carry out a variety of essential cellular processes. Understanding their function and mechanics requires knowing their in situ structural organisation, which is barely accessible to classical structural biology techniques (EM, NMR, crystallography). Recently developed superresolution microscopy techniques however are ideal tools that allow us to study these assemblies in their natural cellular environment and to understand their modus operandi.

In our group, we push the limits of the technology by developing optical, biological and computational methods for superresolution microscopy:

We are developing novel techniques to achieve highest 3D resolution of single fluorophores using Supercritical Angle Localization Microscopy and correlative superresolution and electron microscopy, and are implementing quantitative superresolution imaging based on counting reference standards. Lattice-light sheet microscopy allows us to dynamically visualise structures in thick samples and organisms.

High-content superresolution microscopy and a computational analysis framework enables the acquisition of large datasets of structures with powerful statistics.

In the past, we introduced nanobodies as versatile superresolution labels and pioneered superresolution microscopy in yeast, where strain libraries with tags and mutations allow system-wide superresolution studies.

We then apply our newly developed technologies to exciting cell biological systems:

In one project, we study the complex and dynamic protein machinery that performs clathrin-mediated endocytosis in yeast. Using automated high-content superresolution imaging and quantitative data analysis, we determined how more than a dozen endocytic proteins are organised at the nanoscale. The architectural principles we discovered allowed us to understand how the endocytic machinery achieves remarkably high regularity and efficiency. Our vision is to reconstruct the time-resolved distributions of all endocytic proteins and integrate this data with mathematical modelling, to understand key aspects of the endocytic mechanism, including how the machinery assembles, how membrane curvature is induced and how vesicle scission is mediated.

In other projects, we are studying the structure of the kinetochore, we are investigating intracellular aggregation of Parkinsons’ alpha-synuclein and we aim at reconstructing the 3D organisation of DNA in a cell nucleus.

Future projects and goals

Our vision is to further extend superresolution microscopy as a tool for structural cell biology in situ. We aim to push its limits on all fronts to establish a technique which combines nanometre 3D resolution with maximum labelling efficiencies, absolute measurements of protein copy numbers, precise multi-colour measurements, high-throughput for large scale statistics and novel data analysis approaches, to address the vast array of exciting biological questions at the nanoscale, which are becoming accessible only now.

People

Ries Lab 2018

Group Members

Jonas Ries
Group Leader
Konstanty Cieslinski
Konstanty Cieslinski
PostDoc
Joran Deschamps
Joran Deschamps
Scientific Officer
Robin Diekmann
Robin Diekmann
PostDoc
Philipp Hoess
Philipp Hoess
PhD Student
Yiming Li
Yiming Li
PostDoc
Ulf Matti
Ulf Matti
Research Technician
Aline Tschanz
Aline Tschanz
PhD Student
Jervis Vermal Thevathasan
Jervis Vermal Thevathasan
PhD Student
Yu-Le Wu
Yu-Le Wu
PhD Student
Anindita Dasgupta
Anindita Dasgupta
Master Student
Maurice Kahnwald
Maurice Kahnwald
Trainee

Associated PostDocs

Tim Pollex
Arina Rybina
Rafael Martins Galupa
Markus Mund

Open positions

We are always looking for motivated Masters students and interns with a background in physics, programming or biology. Please contact Jonas directly.

If you want to join as a PhD student, please note that admission is exclusively via the EMBL PhD program.

Alumni

Name Position Topic Period Current affiliation
Alejandro Colchero Master Student Optimizing Dual-Color SMLM 04.2018 - 09.2018 University of Madrid
Sudheer Kumar Peneti Master Student Quantifying labeling efficiency in SMLM 03.2018 - 07.2018 Newcastle University
Rayka Karimi Intern 4 Pi software development 04.2018 - 06.2018  
Julia Botta Intern Counting by SMLM and Kinetochore 02.2018 - 04.2018 University of Heidelberg
Daniel Heid Intern Quantifying labeling efficiency in SMLM 01.2018 - 03.2018 University of Heidelberg
Li-Ling Yang PostDoc Inverted lattice light-sheet microscope 06.2014 - 12.2017  
Markus Mund PhD Student & PostDoc Endocytosis 09.2012 - 12.2017 University of Geneva
Sarah Hoerner Master Student Counting with SMLM 06.2017 - 12.2017 Heidelberg University
Daniel Schroeder Master Student Microscopy Development 04.2017 - 10.2017 FU Berlin
Elena Buglakova Intern Modeling of 4Pi-PSF 07.2017 - 09.2017  
Krishna Kasuba Intern Protein counting by SMLM 10.2016 - 08.2017 ETH Zürich
Johanna Mehl Intern Superresolution imaging of endocytosis 10.2016 - 04.2017 ETH Zürich
Jooske Monster Intern Superresolution imaging of endocytosis 10.2016 - 12.2016 Utrecht University
Joanna Zareba Intern Fluorophores 07.2016 - 10.2016 Chicago University
Katharina Lindner Intern Kinetochore 01.2016 - 05.2016 Heidelberg University
Tooba Quidwai Intern Superresolution imaging of platelets 04.2014 – 08.2015 Edinburgh
Jan van der Beek Intern Superresolution imaging of endocytosis 12.2014 – 07.2015 Utrecht University
Rohit Prakash Intern Superresolution imaging of endocytosis 11.2013 – 03.2015 Rochester University
Andreas Rowald Intern Microscopy development 09.2014 – 02.2015 Erlangen University
Nagaraja Chandramohan Intern Programming 01.2014 – 12.2014 HITS
Sven Spachmann Bachelor student Co-localization in superresolution 05.2014 – 07.2014  
Sunil Kumar Dogga Intern Endocytosis 12.2013 – 02.2014  
Sanchari Datta Intern Endocytosis 06.2013 – 07.2013  
Meet Mukesh Paswan Intern Programming 06.2013 – 07.2013  
Johannes Bues Intern Superresolution in yeast 04.2013 – 05.2013  

Software

SMAP

SMAP (Superresolution Microscopy Analysis Platform) is a comprehensive software framework for single-molecule localization microscopy that can be used for fitting of raw data and subsequent analysis.

It can be obtained from GitHub

fit3Dcspline

fit3Dcspline is a GPU based 3D single molecule fitter for arbitrary, experimental point spread functions (PSF).

It was published in Nature Methods and can be obtained from GitHub

Data obtained from the standalone version can be visualized using Felix Woitzel's Pointcloud-Loader

Publications

2018

Systematic Nanoscale Analysis of Endocytosis Links Efficient Vesicle Formation to Patterned Actin Nucleation
Mund M, van der Beek JA, Deschamps J, Dmitrieff S, Hoess P, Monster JL, Picco A, Nédélec F, Kaksonen M, Ries J.
Dual-Color and 3D Super-Resolution Microscopy of Multi-protein Assemblies.
Hoess P, Mund M, Reitberger M, Ries J.
Methods Mol Biol 1764:237-251. doi: 10.1007/978-1-4939-7759-8_14
Site-specific labeling of Affimers for DNA-PAINT microscopy.
Schlichthaerle T, Eklund A, Schueder F, Strauss M, Tiede C, Curd A, Ries J, Peckham M, Tomlinson D, Jungmann R.
Angew Chem Int Ed Engl doi: 10.1002/anie.201804020
Real-time 3D single-molecule localization using experimental point spread functions.
Li Y, Mund M, Hoess P, Deschamps J, Matti U, Nijmeijer B, Sabinina VJ, Ellenberg J, Schoen I, Ries J.
Nat Methods doi: 10.1038/nmeth.4661
ChromoTrace: Computational reconstruction of 3D chromosome configurations for super-resolution microscopy.
Barton C, Morganella S, Ødegård-Fougner Ø, Alexander S, Ries J, Fitzgerald T, Ellenberg J, Birney E.
PLoS Comput Biol 14(3) doi: 10.1371/journal.pcbi.1006002

2017

Nanoscale invaginations of the nuclear envelope: Shedding new light on wormholes with elusive function.
Schoen I, Aires L, Ries J, Vogel V.
Nucleus 8(5):506-514. doi: 10.1080/19491034.2017.1337621
Aurora-B kinase pathway controls the lateral to end-on conversion of kinetochore-microtubule attachments in human cells.
Shrestha RL, Conti D, Tamura N, Braun D, Ramalingam RA, Cieslinski K, Ries J, Draviam VM.
Nat Commun 8(1) doi: 10.1038/s41467-017-00209-z
Nanoscale invaginations of the nuclear envelope: Shedding new light on wormholes with elusive function.
Schoen I, Aires L, Ries J, Vogel V.

2016

Acetylated tubulin is essential for touch sensation in mice
Morley SJ, Qi YM, Iovino L, Andolfi L, Guo D, Kalebic N, Castaldi L, Tischer C, Portulano C, Bolasco G, Shirlekar K, Fusco CM, Asaro A, Fermani F, Sundukova M, Matti U, Reymond L, De Ninno A, Businaro L, Johnsson K, Lazzarino M, Ries J, Schwab Y, Hu J, Heppenstall PA.
eLife 5 doi: 10.7554/eLife.20813
Efficient homogeneous illumination and optical sectioning for quantitative single-molecule localization microscopy.
Deschamps J, Rowald A, Ries J.
Opt Express 24(24):28080-28090. doi: 10.1364/oe.24.028080
Specific protein labeling with caged fluorophores for dual-color imaging and super-resolution microscopy in living cells.
Hauke S, von Appen A, Quidwai T, Ries J, Wombacher R.
Chem Sci 8(1):559-566. doi: 10.1039/C6SC02088G
Bax assembly into rings and arcs in apoptotic mitochondria is linked to membrane pores.
Salvador-Gallego R, Mund M, Cosentino K, Schneider J, Unsay J, Schraermeyer U, Engelhardt J, Ries J, García-Sáez AJ.

2015

Molecular architecture of native fibronectin fibrils.
Früh SM, Schoen I, Ries J, Vogel V.
Nat Commun 6 doi: 10.1038/ncomms8275
Absolute Arrangement of Subunits in Cytoskeletal Septin Filaments in Cells Measured by Fluorescence Microscopy.
Kaplan C, Jing B, Winterflood CM, Bridges AA, Occhipinti P, Schmied J, Grinhagens S, Gronemeyer T, Tinnefeld P, Gladfelter AS, Ries J, Ewers H.
Nano Lett. 15(6):3859-3864. doi: 10.1021/acs.nanolett.5b00693
Visualizing the functional architecture of the endocytic machinery.
Picco A, Mund M, Ries J, Nédélec F, Kaksonen M.
eLife 4 doi: 10.7554/eLife.04535
Scanning fluorescence correlation spectroscopy on biomembranes.
Hermann E, Ries J, García-Sáez AJ.
Methods Mol. Biol. 1232:181-197. doi: 10.1007/978-1-4939-1752-5_15
Show older publications

Contact

Ries Lab

EMBL Heidelberg
Meyerhofstr. 1
69117 Heidelberg

Room 402
Phone number: +49 6221 3878199
E-Mail: ries(at)embl.de

Ries Lab website at www.embl.de
European Molecular Biology Laboratory