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The Cordes lab “Physical and Synthetic Biology” specializes in the development and application of novel spectroscopy and imaging techniques that allow to map structure and function of biomolecules and (bio)chemical processes in space and time. For this the group uses a combination of optical techniques (single-molecule fluorescence spectroscopy & super-resolution imaging) with nanoscale sensors, i.e., fluorescent probes. The Cordes group follows a question-driven approach to gain insight into the molecular mechanisms of membrane transport and molecular motors (area 1), as well as chemical reactions and catalysis (area 2). Finally we are active in developing fluorescent probes and biophysical assays to characterize (bio)chemical processes and structures in vitro and in vivo (area 3).

 

Research Area 1: Molecular mechanisms of membrane transport

Membrane transport proteins play crucial roles in numerous cellular processes. Despite their importance, all proposed molecular models for transport are based on indirect evidence due to the inability of classical biophysical and biochemical techniques to directly visualize structural dynamics. This lack of data to validate mechanistic models for transport concerns both primary and secondary active transporters. The Cordes group is using single-molecule tools to decipher the molecular mechanisms of transport of these complex machines directly. This novel biophysical research area will support the development of new strategies against pathogenic bacteria or multi-drug resistant cancer cells.

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Research Area 2: Novel approaches to unravel fundamental principles in chemistry and catalysis

We further use our expertise and techniques to understand mechanisms of “classical” chemical and catalytic problems. Especially single-molecule tools might play an important role in understanding the fundamental principles of catalytic activity. Often less than 1% of the molecules in homogenous catalysis or active sites in heterogenous catalysis fully dominate the outcome of a chemical reaction seen at a macroscopic level. Given the importance of mechanistic insights for the development of chemical reactions, it is surprising that the application of single-molecule and single-particle fluorescence microscopy is not yet common. Our group explores the use of sensitive fluorescence microscopy and time-resolved spectroscopy techniques to chemical and catalytic problems and their reaction mechanisms.

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Research Area 3: Development of new spectroscopy and microscopy methods

In relation to the mechanistic (bio)chemical focus, the PSB group develops experimental tools based on time-resolved spectroscopy, photophysics and photochemistry.

Probe development, spectroscopy & biolabelling

Fluorescence emission has evolved to an indispensable tool in the life sciences, e.g., as a general contrast mechanism for imaging, biochemical assays, medical screening, or DNA-sequencing. The merits of these applications and their information content are not limited by physical instruments, but by the performance of the employed fluorescent reporters. These intrinsically suffer from transient excursions to dark states limiting signal height and stability as well as from irreversible photochemical destruction (“photobleaching”) that restricts their observation time. The Cordes lab is developing novel fluorophores with self-healing or other functional properties imparted by the covalent linkage of e.g., photostabilizers to the fluorophore. These vastly improved properties have proven to be crucial for advanced fluorescence applications and super-resolution microscopy (STED & STORM). Current projects focus on optimization of chemical linkage of photostabilizer-dye conjugates and their application in live-cells.

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Novel biophysical assays
 

The Cordes group is using their photophysical expertise to develop novel biophysical tools to answer mechanistic questions in molecular biology. In typical single-molecule assays used for structural mapping of protein complexes, only a single distance is determined per experiment. One of the recent developments used a combination of photophysical (or photochemical) properties to obtain a multi-dimensional assay with higher information content: While a fluorescence resonance energy transfer process (FRET) reports on the distance (changes) between the two fluorophores the novel assay simultaneously allows to detect the presence of and distance to another yet unlabelled biomolecule via protein-induced fluorescence enhancement. Alternatively, we recently explored the use of caged fluorophores for smFRET experiments.

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