Physics and Engineering

Enabling technology for a host of experimental methods

At EMBL, many groups incorporate different areas of Physics and Engineering into their research, such as biophysics, optics, spectroscopy, imaging, robotics and micro engineering.

These disciplines provide enabling technology for many biological applications such as studies on the cytoskeleton and cell mechanics, structural biology, microscopy, single cell/single molecule assays and high-throughput screening.

EMBL units researching Physics and Engineering

EMBL offers a unique opportunity to be involved in highly interdisciplinary projects in the life sciences, such as:

Mechanobiology at the cell surface

scientific equipment

The Diz-Muñoz group uses atomic force microscopy and live cell imaging to characterise and modify mechanical properties of cells and tissues. We also aim to develop non-contact techniques to measure and control such properties.

This will allow us to pursue a comprehensive understanding of the specific contribution of different force inputs (e.g. adhesion, membrane tension, contractility, stiffness) for cell polarization. Moreover, this will provide an avenue to assess how these inputs affect signaling and set a framework to theoretically describe the complex reality of cell migration.

Selected publications

Membrane Tension Acts Through PLD2 and mTORC2 to Limit Actin Network Assembly During Neutrophil Migration

Alba Diz-Muñoz, Kevin Thurley, Sana Chintamen, Steven J. Altschuler, Lani F. Wu, Daniel A. Fletcher, and Orion D. Weiner

PLoS Biology 2016

vol. 14(6)

Use the force: membrane tension as an organizer of diverse cellular functions

Alba Diz-Muñoz, Daniel A. Fletcher and Orion D. Weiner

Trends Cell Biol 2013

vol. 23 (2)

Control of directed cell migration in vivo by membrane to cortex attachment

Alba Diz-Muñoz , Michael Krieg , Martin Bergert, Itziar Ibarlucea-Benitez, Daniel Muller, Ewa Paluch and Carl-Philipp Heisenberg

PLoS Biology 2010

vol. 8 (11)

Robotics and process development for MX and Cryo-EM

scientific equipment

Our team develops instruments and methods for X-ray scattering experiments within the EMBL/ESRF Structural Biology group and contributes to the development of the EMBL@PETRA-III beamlines in Hamburg.

Our core activity is to develop High precision diffractometers and automated sample environments for MX and SAXS beamlines. Recent example is a sample changer based on a 6 axis industrial robot and patented EdgeDewar (Picture). This system called FlexED8 holds up to 252 miniSpine samples holders in 7 pucks maintained in an ice free environment. The Flex technology is being adapted to equip the ESRF MX beamlines and coupled to our CrystalDirect harvester developed in collaboration with the Grenoble HTX lab.

Our technical expertise in high precision mechanics, cryogenics, optics, electronics and software, associated with the scientific input provided by the Synchrotron Crystallography Team ensures the success of our instruments. Most of them are transferred to industry and commercialised worldwide with the support of EMBLEM, the commercial and technology transfer arm of EMBL.

Selected publications

New beamline dedicated to solution scattering from biological macromolecules at the ESRF

P. Pernot*, A. Round*, P. Theveneau, T. Giraud; R. Nogueira-Fernandes, D. Nurizzo, D. Spruce, J. Surr, S. McSweeney, F. Felisaz, L. Foedinger, A. Gobbo, J. Huet, C. Villard, F. Cipriani

J. Phys.: Conf. Ser. 2010

*247* 012009 *Joint first authorship

Automation of sample mounting for macromolecular crystallography

Cipriani, F., Felisaz, F., Launer, L., Aksoy, J.S., Caserotto, H., Cusack, S., Dallery, M., di-Chiaro, F., Guijarro, M., Huet, J., Larsen, S., Lentini, M., McCarthy, J., McSweeney, S., Ravelli, R., Renier, M., Taffut, C., Thompson, A., Leonard, G.A. & Walsh, M.A.

Acta Crystallogr D Biol Crystallogr. 2006

Oct;62(Pt 10):1251-9. Epub 2006Sep 19 PubMed

Protein microcrystals and the design of a microdiffractometer: current experience and plans at EMBL and ESRF/ID13

Perrakis, A., Cipriani, F., Castagna, J.C., Claustre, L., Burghammer, M., Riekel, C. & Cusack, S.

Acta Crystallogr D Biol Crystallogr 1999

Oct;55 ( Pt 10):1765-70 PubMed

Functional dynamics of nuclear structure during the cell cycle

scientific image

Engineering and physics are essential in two areas of our work.

  1. To identify and characterize cell division genes systematically, we need novel high throughput methods. In our group we:
  1. In order to interpret protein dynamics inside cells we need to understand their rheology. To this end we are interested in the physical properties of the microenvironment in the cell nucleus, which we probe by biophysical methods and model in computer simulations.

Selected publications

Phenotypic profiling of the human genome by time-lapse microscopy reveals cell division genes

Neumann, B., Walter, T., Heriche, J.K., Bulkescher, J., Erfle, H., Conrad, C., Rogers, P., Poser, I., Held, M., Liebel, U., Cetin, C., Sieckmann, F., Pau, G., Kabbe, R., Wünsche, A., Satagopam, V., Schmitz, M.H., Chapuis, C., Gerlich, D.W., Schneider, R., Eils, R., Huber, W., Peters, J.M., Hyman, A.A., Durbin, R., Pepperkok, R. & Ellenberg J.

Nature 2010

Apr 1;464(7289):721-7

Molecular crowding affects diffusion and binding of nuclear proteins in heterochromatin and reveals the fractal organization of chromatin

Bancaud, A., Huet, S., Daigle, N., Mozziconacci, J., Beaudouin, J. & Ellenberg, J.

EMBO J. 2009

Dec 16;28(24):3785-98

Dissecting the contribution of diffusion and interactions to the mobility of nuclear proteins

Beaudouin, J., Mora-Bermudez, F., Klee, T., Daigle, N. & Ellenberg, J.

Biophys J. 2006

Mar 15;90(6):1878-94

Synchrotron Instrumentation for structural biology

scientific equipment model

Research carried out at the EMBL Hamburg Unit utilizes the extremely brilliant Synchrotron radiation X-ray intensity produced by particle accelerators at DESY for structural investigations in biology. Experiments are carried out in Small angle solution scattering (SAXS) and X-ray crystallography (PX).

Each of these methods has specific instrumentation needs and our groups design, construct, build and commission the appropriate equipment. Our activities include mechanical engineering, vacuum technology, X-ray optics, data acquisition and control electronics and software. Because of the wide spectrum of skills and competences required our group members include physicists, mechanical, electronic and software engineers as well as skilled technicians in these fields.

EMBL is building and will operate three beamlines on one of the world leading synchrotron radiation sources, PETRA III. In this context major challenges and opportunities in the field of beamline instrumentation, sample handling, control electronics and software have to be mastered.

Selected publications

The concept of EMBL beamline control at PETRA III

Ristau, U., Di Castro, M. , Pazos, A. & Fiedler, S.

Proceedings of PCaPAC08 2008

MOZ02, 22-24

Upgrade of the small-angle X-ray scattering beamline X33 at the European Molecular Biology Laboratory, Hamburg

Roessle, M.W., Klaering, R., Ristau, U., Robrahn, B., Jahn, D., Gehrmann, T., Konarev, P., Round, A., Fiedler, S., Hermes, C. & Svergun, D.

Journal of Applied Crystallography 40 2007


New beamlines for protein crystallography at the EMBL Outstation Hamburg

Hermes, C. Gehrmann, T., Jahn, D., Ristau U., Robrahn, B. & Siambanis, T.

AIP Conference Proceedings 705 2004


Statistical Computing and Mathematical Modeling

scientific diagram

Progress in biology is driven by technology. High throughput sequencing and microscopy require sophisticated statistical and computational operations in order to exploit their potential. To understand (and, eventually, manipulate) biological systems, all available data about them needs to be integrated into computable maps and mathematical models. Ideas and techniques from physics, mathematics, statistics, computer science and engineering are the crucial drivers for our research.

Selected publications

Independent filtering increases detection power for high-throughput experiments

Richard Bourgon, Robert Gentleman, and Wolfgang Huber

PNAS 2010

107(21):9546-9551 (11 citations) DOI

Mapping of signalling networks through synthetic genetic interaction analysis by RNAi

Thomas Horn, Thomas Sandmann, Bernd Fischer, Elin Axelsson, Wolfgang Huber, and Michael Boutros

Nature Methods 2011

8(4) DOI

High-resolution mapping of meiotic crossovers and non-crossovers in yeast

Eugenio Mancera, Richard Bourgon, Alessandro Brozzi, Wolfgang Huber, and Lars M. Steinmetz

Nature 2008

454(7203):479-485 (76 citations)

More publications

Synchrotron Crystallography

scientific equipment

The Synchrotron Crystallography team works in close collaboration with the Structural Biology Group of the European Synchrotron Radiation Facility (ESRF in the design, construction and operation of macromolecular crystallography (MX) and biological small angle X-ray scattering (bioSAXS) beamlines.

In addition, we are responsible for the management of the CRG beamline BM14 at the ESRF, which is operated in partnership with the Indian government and ESRF. We also participate in the development of instruments, software and novel methodologies for sample handling and data collection strategies, which is carried out in close collaboration with the Papp team.

Finally the team is active in a number of collaborative projects with other synchrotrons in Europe, such as EDNA and the kappa working group.

Selected publications

Translation calibration of inverse kappa goniometers in macromolecular crystallography

S. Brockhauser, K. I. White, A. A. McCarthy, R. B. G. Ravelli

Acta Cryst. 2011

A67 (in press)

New beamline dedicated to solution scattering from biological macromolecules at the ESRF

P. Pernot*, A. Round*, P. Theveneau, T. Giraud; R. Nogueira-Fernandes, D. Nurizzo, D. Spruce, J. Surr, S. McSweeney, F. Felisaz, L. Foedinger, A. Gobbo, J. Huet, C. Villard, F. Cipriani

J. Phys.: Conf. Ser. 2010

*247* 012009 *Joint first authorship

A decade of user operation on the macromolecular crystallography MAD beamline ID14-4 at the ESRF

A. A. McCarthy, S. Brockhauser, D. Nurizzo, P. Theveneau, T. Mairs, D. Spruce, M. Guijarro, M. Lesourd, R. B. G. Ravelli, S. McSweeney

J. Synchrotron Rad. 2009

16, 803–812

Advanced optical techniques for deep tissue microscopy

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The Prevedel group develops new optical approaches and techniques to non-invasively image dynamic cellular processes in living tissue. To advance the frontiers of deep tissue microscopy we integrate concepts from diverse physical fields, such as wavefront engineering, photo-acoustics and computational imaging.

At the same time, we engineer innovative optical and mechanical hardware solutions for our microscopes to adapt them to particular samples and imaging conditions. In order to interpret our recordings, we also develop custom software to automate the extraction of relevant parameters from our data.

Selected publications

Optimizing and extending light-sculpting microscopy for fast functional imaging in neuroscience

Rupprecht P, Prevedel R, Groessl F, Haubensak WE, Vaziri A.

Biomed Opt Express 2015

6:353-368. doi: 10.1364/BOE.6.000353 Europe PMC

Simultaneous whole-animal 3D imaging of neuronal activity using light-field microscopy

Prevedel R, Yoon YG, Hoffmann M, Pak N, Wetzstein G, Kato S, Schrodel T, Raskar R, Zimmer M, Boyden ES, Vaziri A.

Nat Methods 2014

11:727-U161. doi: 10.1038/NMETH.2964 Europe PMC

Brain-wide 3D imaging of neuronal activity in Caenorhabditis elegans with sculpted light

Schrodel T, Prevedel R, Aumayr K, Zimmer M, Vaziri A.

Nat Methods 2013

10:1013-1020. doi: 10.1038/NMETH.2637 Europe PMC

Superresolution Microscopy

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In order to investigate biological questions that were previously inaccessible because of the limited resolution of light microscopes, we are developing novel superresolution microscopy tools. The design and implementation of advanced microscopes is crucially based on physics and engineering such as optics, mechanical and electrical engineering, image analysis and software development.

Currently we are developing the following tools:

Selected publications

Superresolution Imaging of Amyloid Fibrils with Binding-Activated Probes

Ries, J., Udayar, V., Soragni, A., Hornemann, S., Nilsson, K.P., Riek, R., Hock, C., Ewers, H., Aguzzi, A.A. & Rajendran, L.

ACS Chem Neurosci. 2013

Apr 22 Europe PMC

A simple, versatile method for GFP-based super-resolution microscopy via nanobodies

Ries, J., Kaplan, C., Platonova, E., Eghlidi, H. & Ewers, H.

Nat Methods 2012

Jun;9(6):582-4. doi: 10.1038/nmeth.1991. Epub 2012 Apr 29 Europe PMC

Binding-activated localization microscopy of DNA structures

Schoen, I., Ries, J., Klotzsch, E., Ewers, H. & Vogel, V.

Nano Lett. 2011

Sep 14;11(9):4008-11. Epub 2011 Aug 18 Europe PMC

From microscopy to mycology, from development to disease modelling, EMBL researchers cover a wide range of topics in the biological sciences.