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Research
News
25. - 28. April 2013
Again we go for retreat at the Lago di Como (Italy). Excellent science, food, drinks, culture and discussions. Meaningful pictures are available on the group file server.
26. April 2013
A big big good bye and a farewell to Christian Bippes. After having been for more than 8 years with the lab Christian decided to join Nanosurf, an AFM company close to Basel. After having beeing inspired by Christians art of cooking every labmember gave her/his best to prepare a speciality of the home country. It was a long evening we enjoyed Swiss, Italian, German, Spanish, Indian, Scottish, US, Argentinian, Chinese, Finnish, Armenian and Russian food. It was fantastic and Christian is welcome to join and leave the lab as often as he can ;-)) Best wishes from us all to Christian - it was wonderful having you as colleague!
15. - 18. April 2013
Global challenges - Opportunities for Nanotechnology! We organize the workshop for PhD students and postdocs at San Servolo at Venice, Italy. The organisators Christoph Gerber from the Swiss Nanoscience Institute (Basel), Hermann Gaub from the Center for Nanoscience (CeNS, Munich), and we from the ETH Zurich together with the Jean-Marie Lehn, Gerd Binnig and Viola Vogel coached the PhD students and postdocs to foster the awareness for the global challenges by an analysis of the current major problems. More information can be found at: http://www.cens.de/international/joint-workshops/globalchallenges13/
15. April 2013
Welcome to Richard Newton from Scotland (we learn that this does not mean that Rich is from England!!!). Rich is our newest, youngest and xxxx PhD student.
2. April 2013
Welcome to Roland Goers! Roland joins our group as a master student. He will do his master thesis together with Wolfgang Meiers group (Uni Basel) and Dimitrios Fotiadis group (Uni Bern).
26. January 2013
Good bye and farewell to Michael Zocher. After having been working, publishing, and graduating Michael decided that its time to support innovations. He will continue his career as a patent attorney at Munich. Good luck, have fun, and go and staple as much money as you can! ;-)
07. January 2013
Happy new year and a very warm welcome to our new PhD students Alessandra Franchino (Italy) and Estefania Mulvihill (Argentina/Italy). Alessandra received her Masters in molecular and cellular biotechnology from the University Milano and after this worked shortly in a biotech company at the Netherlands. Estefania received her masters in biotechnolgy from the university of Florence.
06. January 2013
Kings of the Day
03. January 2013
We sadly say goodbye to Izhar Medalsy. Izhar will join Bruker at Santa Barbara to participate in the development of new AFMs. We will miss him! Mazel tov Izhar!!!
8. Oct 2012
Double congratulations to David Martinez Martin. David received a prestigious EMBO postdoctoral fellowship and the research award from the Spanish Royal Academy.
17. Sept 2012
We welcome David Martinez Martin who will be a new postdoc of our group. David has an impressive background on building different AFM for the multifunctional high-resolution imaging. In a joint project with Christoph Gerber and Tony Hyman David will develop a new AFM for biophysical measurements.
4. July 2012
The triple PhD is done! Gratulations to Shiho, Michael, and Martin who all three passed their PhD exams and got their crown ;-)
2. July 2012
PhD defense of Michael Zocher at Basel.
1. July 2012
Welcome Tania! From today on Tania Serdiuk will join our laboratory as PhD student. Tania did her masters at Kiev National Taras Shevchenko University, Ukraine, and at the Institute of Nanotechnologies INSA, Lyon, France.
29. June 2012
PhD defense of Martin Stewart at Dresden.
28. June 2012
PhD defense of Shiho Kawamura at Basel.
27. June 2012
We congratulate David Martinez Martin for being awarded by a long-term EMBO postdoctoral fellowship. David will join our lab soon to develop a new promising nanotechnology to quantify cellular processes.
22-24. March 2012
Group retreat at the lake of Como, Italy.
20. January 2012
Gratulations to Patrick Bosshart who today passed his PhD exams. The extensive party destroyed many brain cells of (formerly) talented students ;-) Pictures are under censorship and available from patrick who is now joining the Dimitrios Fotiadis group at the University of Berne.
January 2012
We welcome our new PhD students Mitasha Bharadwaj (India) and Rafayel Petrosyan (Armenia). Mitasha received her MSc Biotechnology from the Amity University, New Delhi. Rafayel received his MSc Nanobiophysics from the TU Dresden, Germany.
1. Januar 2012
Two new stars are born! We all congratulate Johannes Thoma and Nico Strohmeyer for successfully passing their Master Exam.
15. September 2011
'Bienvenue' or "welkom' to Joost te Riet from the University of Nijmegen.
As an EMBO fellow Joost will stay at our lab for 3 months and work on a cell adhesion project.
1. September 2011
A very warm 'benvenuta' to Barbara Sorce. Barbara is a postdoc and Marie Curie Fellow (FP7-SBMP) coming form the University of Bologna and Lecce. In our lab Barbara will develop new nanotechnological approaches to study the mechanics of single cells.
1. September 2011
1. September 2011
A big welcome to Miao Yu. Miao is our new PhD student sponsored by the Chinese Academy of Sciences. In our lab Miao will characterize membrane receptors regulating cell adhesion.
15. August 2011
A very warm 'bienvenue' to Viciane Grimard from the University of Brussels. As EMBO fellow Viciane will stay at our lab for 3 months and work on a single-molecule force spectroscopy project.
5. May 2011
A new star is born! We all congratulate Susanne Wegmann for passing her successful PhD exams at the ETH Zürich. After all formalities have been done she will be the NEW Dr. in our lab. The photo shows Susanne at the beginning of extensive celebrations. Photos at later stage may be available upon request ;-)
15. April 2011
We welcome Iordan Iordanov as a temporary labmember of our group. Iordan is a Marie-Curie-Fellow (FP 7) and performs his PhD at the University Toulouse, France. In our lab Iordan will perform single-molecule studies to characterize structural and functional properties of membrane proteins he prepared for NMR studies.
1. March 2011
We congratulate Clemens Möller for accepting his full professorship in biophysics at the Life Sciences Faculty at the Albstadt-Sigmaringen University, Germany. Clemens was the first PhD student of our lab and gained considerable experience as research group leader at the pharmacological industry. More info at: http://www.hs-albsig.de
1. February 2011
A very welcome to Ulf Hensen, our new scientist on the block!!! Ulf hast obtained his PhD at MPI of Biophysical Chemistry Göttingen. In the scientific group of Helmut Grubmüller, Ulf has worked using and developing tools for molecular dynamics (MD) simulations of proteins. Infos at http://www.mpibpc.mpg.de/home/grubmueller/index.html
1. December 2010
We congratulate Harald Janovjak for his new position as Assistant Professor at the I.S.T. Austria.
Harald was one of the first PhD students at our laboratory and did a great postdoc at Berkeley. Infos at http://www.ist.ac.at/research/research-groups/janovjak-group/
23. November 2010
We congratulate Michael Krieg for receiving the Deutscher Studienpreis of the Körber-Stiftung.
The price will give Michael a great time at USA. From December 2010 on Michael will join the Stanford School of Medicine as a postdoc.
03. November 2010
We welcome our new lab member Nico Strohmeyer.
Nico is a Master student of our lab.
02. November 2010
We congratulate Martin Stewart, Jonne Helenius and Ramanthan Subramaniam to their newest paper "Hydrostatic pressure and the actomyosin cortex drive mitotic cell rounding" which was accepted by Nature!
01. November 2010
We welcome our new lab member Moritz Pfreundschuh.
Moritz is a PhD student of the Molecular Life Science Graduate School of ETH and University Zürich.
01. Oktober 2010
We welcome our new lab member Cédric Cattin.
Cédric is a PhD student who received his Msc in Nanosciences at the University of Basel.
Quantifying biological processes from cells to molecules
Molecular interactions drive all processes in life. They determine the molecular crosstalk and build the basic language of biological processes. Molecular interactions fold the polypeptide into the functional protein, stabilize the structure, or lead to protein misfolding. These molecular forces determine protein-protein interactions, switching on and off ion channels, ligand-binding, the functional states of receptors, and the supramolecular assembly of molecular machines to functional units. On more complex scales molecular interactions guide cell adhesion, migration, communication and differentation. Other examples show how they sculpture reaction pathways of biological processes. Because of this enormous importance it is one pertinent demand in life sciences to characterize how these interactions are established and how they guide biological processes ranging from the molecular to cellular scale. To decipher fundamentals of this biological language, we have pioneered two bionanotechnological methods, single-molecule atomic force microscopy (AFM) and single-molecule force spectroscopy (SMFS), which allows detecting inter- and intramolecular interactions of native membrane proteins. Recent extensions of both methods allow to image cells at nanometer resolution and to study interactions of single cells at molecular resolution using single-cell force spectroscopy (SCFS).
Learning to detect and interpret molecular forces and interactions
SMFS and SCFS allow detecting inter- and intramolecular forces and reveal intriguing insights into the forces that stabilize biological structures, determine various biological interactions, and drive biological processes. Originating from the experimental setup of the force spectroscopy it was thought that the interactions detected would be mostly of mechanical nature. However, it has become clear that force spectroscopy detects molecular interactions resulting from different physical and chemical origins. The ongoing challenge is to dissect and determine the extent to which various physical interactions contribute to a certain force detected in biological systems. For example, what are the life-times of these interactions? How do they contribute to ligand- and inhibitor-binding? How do these interactions follow each other thereby forming an interaction network? How does deleting or adding an interaction (e.g. by mutations) affect complex interaction networks of membrane proteins? How does a cell control interactions to direct membrane proteins into dynamic functional assemblies? Typically such questions are experimentally addressed using techniques from structural biology, where structural details help decipher the nature of theses interactions. Since these techniques only provide static pictures they are inherently limited in addressing these questions. Cell biological approaches on the other side rather provide descriptive than quantitative insights into molecular mechanisms. Certainly, with the existing and the forthcoming generations of SMFS and SCFS it will be possible to characterize and understand the forest of interactions and their contributions to complex cellular processes.
Quantifying biological interactions and mechanisms
We continuously develop and establish experimental approaches of single-molecule and single-cell force spectroscopy to quantify cellular interactions down to the resolution of single proteins. It became even possible to take a look into single proteins and to precisely locate the interactions established between proteins and within a protein. In most cases this feasibility could be demonstrated on individual membrane proteins by mapping the interactions of their secondary structures. Nowadays, it can be investigated how their inter- and intramolecular interactions alter upon environmental changes such as caused by temperature, electrolyte or protein-protein interactions. Other examples quantify how mutations destabilize membrane proteins leading to malfunction or how proteins interact with a receptor to initiate signal transduction. Molecular interactions occurring upon ligand-binding thereby activating a transporter can be detected and structurally located. In recent experiments we quantify the mechanisms by which different drugs act to modulate the functional states of transporters, carriers and G-protein coupled receptors.
Closing the gap: Quantifying living cells at molecular scale
SCFS uses a single living cell as a probe. With this probe it becomes possible to detect cellular interactions with another cell or a substrate. In most cases such interactions are of adhesive nature and can be divided into specific and unspecific. Cell surface receptors can bind to a variety of ligands to which they show intrinsic specificity. Such ligand-binding can initiate signaling that is taken by the cell to properly respond to its environment. Using SCFS it has become possible to quantify the specific interaction mechanisms of single cell surface receptors of living cells. Differential SCFS allows quantifying how ligand-binding of one kind of receptor modulates the binding affinity of another kind of a cell surface receptor. Such process of one receptor regulating another is called crosstalk. We are now at the beginning to quantify the crosstalk of cell surface receptors and how it contribute to cellular processes such as adhesion, migration and differentiation. Cell adhesion is not only a challenging topic in modern cell biology, but also important for biotechnological applications, tissue engineering, medicine and developmental biology. Several thousand papers having the topic cell adhesion are published every year in international journals. We are convinced that methods of quantifying mechanisms that regulate cell adhesion to molecular scale will find broad interest in the future.
Cartoon showing the detection of molecular interactions of single living cells. The bionanotechnological technique CellHesionTM developed in the laboratory of cellular machines is now internationally sold as the standard lab equipment to characterize cellular adhesion down to the contribution of single molecules.
Overview articles on the topic from the group
- ‘Five challenges to bringing single-molecule force spectroscopy into the living cell’
Y.F. Dufrene, E. Evans, A. Engel, J. Helenius, H.E. Gaub & D.J. Müller
Nature Methods (2011) 8, 123-127.
- ‘Force probing surfaces of living cells to molecular resolution’
D.J. Müller, J. Helenius, D. Alsteens & Y.F. Dufrene
Nature Chemical Biology (2009) 5, 383-390.
- ‘Vertebrate membrane proteins: Structure, function and insights from biophysical approaches’
D.J. Müller, N. Wu & K. Palczewski
Pharmacological Reviews (2008) 60, 43-78.
- ‘Atomic force microscopy as a multifunctional molecular toolbox in nanobiotechnology’
D.J. Müller & Y. Dufrene
Nature Nanotechnology (2008) 3, 261-269.
- ‘Single-cell force spectroscopy’
J. Helenius, C.P. Heisenberg, H.E. Gaub & D.J. Müller
Journal of Cell Science (2008) 121, 1785-1791.
- ‘Atomic force microscopy and spectroscopy of native membrane proteins’
D.J. Müller & A. Engel
Nature Protocols (2007) 2, 2191-2197.
- ‘Deciphering molecular interactions of native membrane proteins by single-molecule force spectroscopy’
A. Kedrov, H. Janovjak, K.T. Sapra & D.J. Müller
Annual Review of Biophysics and Biomolecular Structure (2007) 36, 233-260.
- ‘Single-molecule studies of membrane proteins’
D.J. Müller, K.T. Sapra, S. Scheuring, A. Kedrov, P.L. Frederix, D. Fotiadis, & A. Engel
Current Opinion in Structural Biology (2006) 16, 489-495.
- ‘Observing proteins at work with the atomic force microscope’
A. Engel & D.J. Müller
Nature Structural Biology (2000) 7, 715-718.
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