Open positions
The position is part of the new excellence clusters: "Nanoinitiative
Munich" and "Munich Cluster for integrated Protein Science", as well as
of the Sonderforschungsbereich SFB 646 "Networks in genome expression
and maintenance" . 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 Rad26, an enzyme
involved in transcription coupled repair.
Single-molecule techniques have provided a wealth of information for a
huge variety of molecular machines that perform highly specialized
tasks inside of the cell. Many of these machines utilize chemical
energy to drive a process in a cyclic fashion. Due to the crowded
environment inside of the cell and the constant binding and unbinding
of proteins, oftentimes these machines must be able to work against an
external load, in order to overcome transient barriers. Thus they
constitute molecular motors that are driven in a higly efficient
manner. Understanding the general principles that underlie the motor
function is the common underlying theme behind our research.
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.
Transcription coupled repair (TCR), the efficient removal of lesions in
the transcribed strand is extremely important for genome maintenance
and gene expression. CSB/Rad26, an ATPase related to the Swi/Snf
remodeling factors, facilitates TCR. To date, it is not clear, what the
precise role of CSB/Rad26 in TCR is. Our aim is to elucidate details of
the underlying molecular mechanism by studying the behavior of single
Rad26 molecules bound to DNA. A true test for existing models of TCR
can be found by investigating the effect of Rad26 on a polymerase that
is stalled at a specific DNA lesion.
The experiments will be carried out in close collaboration with the lab
of Patrick Cramer (Pol II), the lab
of Karl-Peter Hopfner (Rad26) and
the group of Thomas Carell (DNA lesions).
We are looking for a skilled and motivated 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: Jens
Michaelis
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: Jens Michaelis
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: Jens Michaelis
Wie bewegen sich Enzyme?
Was für Kraefte koennen molekulare Motoren aufbringen?
Warum sind einzelne biomolekulare Maschinen soviel effizienter als
hochentwickelte Motoren der makroskopischen Welt?
| Mit diesen und aehnlichen hochaktuellen Fragen beschaeftigen 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 stuetzen wir uns auf Methoden der Einzelmolekuelfluoreszenz, die es uns ermoeglichen Konformationsaenderungen der Molekuele oder auch deren Bewegungen direkt zu beobachten. Ausserdem koennen wir mit ausgekluegelten Lasersystemen auch die Kraefte messen, die bei molekularen Prozessen auftreten. Mit diesen neuartigen Methoden ist es nun moeglich gaengige Modelle fuer die Funktionsweise der Biomolekuele 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 koennen, aus dem Weg geraeumt werden, und wie gleichzeitig Defektstellen in der DNA repariert werden. Studenten, die neben dem Interesse fuer Chemie, sich auch fuer aktuelle Fragestellungen der Biologie und Physik begeistern, wenden sich bitte an: Jens Michaelis