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Ph.D. thesis:

Single molecule tracking and super-resolution microscopy in living organisms

Within organisms, the individually stochastic but overall finely orchestrated interaction of inanimate biomolecules enables the enigma of life. Single molecule fluorescence experiments allow for an exceptionally detailed view on life processes in the natural environment of cells and organisms and provide functional information with utmost sensitivity and resolution, far beyond of what can be achieved with ensemble measurements. Tracking individual molecules yields quantitative information on kinetic properties such as reaction rate constants and diffusion coefficients.  By combining stochastic activation of fluorophore labels and single molecule localization microscopy, the number of proteins and the spatial distribution and stoichiometry of cellular structures can be obtained with a resolution even better than the optical diffraction limit. Thus, information necessary for a complete understanding and modeling of life processes can be obtained.

In this project, you will develop and set up a novel fluorescence microscope capable of single molecule imaging and super-resolution microscopy in isolated cells and whole organisms and apply the new technique to fascinating biophysical questions in cellular and organismic biology. The project is ideally suited for physics students with a strong background in optics and high interest in biophysical questions. 

If you are motivated and interested in working in a young, dynamic and interdisciplinary research group at the exciting limit between Physics and Biology and at the forefront of technical possibilities, please send an email to: Opens window for sending emailChristof Gebhardt

 


Ph.D. thesis:

Molecular bases of cellular functions

In a cell, myriads of different molecules are corralled together into a crowded environment. Yet, their mutual interactions lead to well-defined cellular structures and enable the cell to perform its vital functions such as gene expression, replication or repair of DNA. The key participating biomolecular species are known for many cellular tasks. To achieve a deeper understanding and thus modeling of cellular processes, we aim to additionally identify the stoichiometry of molecules, the temporal order and dynamics of their interactions and their spatial distribution.
We use and develop modern biophysical and biochemical methods, with a focus on live cell single molecule fluorescence microscopy, to visualize and follow the operation of individual molecules and study their interactions in the natural environment of a living cell.

If you are motivated and interested in working in a young, dynamic and interdisciplinary research group at the exciting limit between Physics and Biology and with cutting-edge technology, please send an email to: Opens window for sending emailChristof Gebhardt

 


Ph.D. thesis or Postdoc position:

Molecular mechanism of transcription and transcription regulation

The aim of this research is to gain insight into the molecular mechanism of eukaryotic transcription by examining the function of the yeast RNA polymerase II (Pol II) and its regulation.
We will use single-molecule fluorescence, a novel technique that eliminates averaging over time and/or ensembles of molecules, to study conformational changes and interactions of Pol II elongation bubbles in real-time. While structural studies have given us a great insight into the molecular architecture behind the transciption process, details of the dynamics of this process are currently not well understood. Single-molecule experiments therefore compliment the structural studies by providing real-time, dynamic information.
Furthermore the complex behavior of the elongation process, where phases of rapid transcription are interrupted by distinct pauses, can be investigated directly by single-molecule force spectroscopy. Changes in transcription velocities and effects of transcription factors can be examined with unprecedented detail, allowing for the test of current models of transcription elongation and termination. A better understanding of the molecular details of the transcription process can lead to important insight on how transcription is regulated in vivo.

We are looking for a skilled and motivated Ph.D student or postdoctoral researcher with a background in biochemistry, biophysics or related fields. If you are interested in fast-paced interdisciplinary research at the border of physics, chemistry and biology and would like to work in an international research atmosphere, send your applications including the name and address of two references to:
Opens window for sending emailJens Michaelis

 


PhD thesis:

Superresolution optical microscopy

For a long time it has been believed that resolution in optical microscopy is limited to about 200nm due to the diffraction of light. For applications of light microscopy in molecular and cellular biology it is, however, extremly important to develop novel methodologies to break this diffraction limit and extend the resolution of optical microscopy down to the level where single proteins can be resolved. The advantage of light microscopy over other existing approaches for applications in biology is that light microscopy allows for the direct investigation of dynamical processes and therefore, besides optical resolution also time resolution is important. A promising technique in this area is the technique of stimulated emission depletion (STED) microscopy. With STED microscopy super-resolution images with video rate time resolution have been demonstrated recently. The aim of the PhD project will be to design and develop a STED microscope for the investigation of higher order chromatin structures. The project is thus at the intersection of physics, chemistry and biology and candidates with a background in biophysics or optical physics are invited to apply for this position.

Interested? Send your applications to: Opens window for sending emailJens Michaelis

 


PhD thesis:

Nanomechanics of DNA-protein interaction

Enzymes, such as polymerases, helicases or translocases bind to DNA and catalyze biological processes with high specificity and fidelity. We are interested in understanding the underlying molecular mechanisms that drive these marvelous nano-machines. In well-defined in vitro assays we study one molecule at a time with high spatial, and temporal resolution. We use single-molecule fluorescence techniques, to monitor conformational changes as well as movement and rotation. Details about the mechanical properties and mechanisms are elucidated with the help of single-molecule force spectroscopy in optical tweezers, magnetic tweezers or an AFM microscope. We are looking for a skilled and motivated student to combine these two techniques in a new apparatus, to study DNA-protein interaction.

If you are interested in fast-paced interdisciplinary research at the border of physics, chemistry and biology and would like to work in an international research atmosphere, send your applications to: Opens window for sending emailJens Michaelis

 


Masterthesis:

Experimente mit einzelnen Molekülen an der Grenze zwischen Chemie, Biologie und Physik

Mit diesen und ähnlichen hochaktuellen Fragen beschäftigen wir uns in der Nanomechanics Gruppe von Prof. Jens Michaelis. Wir untersuchen einzelne Biomolekuele, indem wir sie aus Zellen isolieren und dann in einer wohldefinierten Umgebung beobachten. Dabei stützen wir uns auf Methoden der Einzelmolekülfluoreszenz, die es uns ermöglichen Konformationsänderungen der Moleküle oder auch deren Bewegungen direkt zu beobachten. Ausserdem können wir mit ausgeklügelten Lasersystemen auch die Krafte messen, die bei molekularen Prozessen auftreten. Mit diesen neuartigen Methoden ist es nun möglich gängige Modelle für die Funktionsweise der Biomoleküle unter die Lupe zu nehmen und neue Einblicke in molekulare Mechanismen zu gewinnen. Wir wollen unter anderem untersuchen wie ein einzelnes Gen kopiert wird, wie dabei andere Proteine, die diesen Prozess behindern können, aus dem Weg geräumt werden und wie gleichzeitig Defektstellen in der DNA repariert werden.
Studenten, die neben dem Interesse für Chemie, sich auch für aktuelle Fragestellungen der Biologie und Physik begeistern, wenden sich bitte an: Opens window for sending emailJens Michaelis