Research

Research Sträßer: Sträßer

Coupling of single steps in gene expression

Gene expression is a fundamental process of living cells that brings the genetic information stored in the DNA to life. The overall goal of the lab is to unravel, how this information is “read” by the cell. The DNA is first transcribed into messenger (m)RNA. The mRNA is processed and packaged by proteins into an mRNP. We focus on the question, how nuclear mRNP formation takes place, how it is integrated with concurrent steps of gene expression and how it influences subsequent life of the mRNA.

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Research Friedhoff: Friedhoff

Molecular enzymology of the DNA mismatch repair (MMR) pathway

The repair of DNA damage is a critical step in maintenance of genome integrity. Errors in DNA repair pathways lead to build up of mutations, genome instability and ultimately result in cancer in humans. The processes involved are executed by complicated molecular machines that execute a carefully choreographed set of activation steps.

We study molecular enzymology of the evolutionary conserved DNA mismatch repair (MMR) pathway from Escherichia coli. To study this dynamic multistep repair pathway we use complementary approaches employing enzymatic, biochemical and biophysical methods to study the protein-nucleic acid and protein-protein interactions (endonuclease, ATPase, helicase). Typical biophysical methods comprise fluorescence spectroscopy (e.g. FRET - steady-state and time-resolved (stopped-flow)), chemical cross-linking (combined with mass spectrometry), interaction analysis (ITC), dynamic light scattering, circular dichroism. In national and international collaborations we combine single molecule analysis, high resolution structural biology and highly time-resolved biochemical and biophysical assays that will allow an integrated vision of the steps in DNA mismatch repair (MMR).

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Research Wende: Wende

Highly specific tailor-made nucleases as essential tools for genome engineering

TALE nucleases and the recently introduced CRISPR-Cas9 system have widely spread and become the methods of choice for genome editing in a wide range of higher organisms. However, critical mechanistic details of the technologies remain largely unknown. Therefore, we investigate the mechanism how these genome targeting tools find their specific target, as well as the thermodynamics and kinetics of DNA binding. Based on these results, we want to improve the specificity of our new designer nucleases and promote their clinical and biotechnological application.

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