One of the fundamental unsolved problems in biology is how proteins attain their proper three dimensional conformations. Heat shock proteins and protein folding catalysts are vital in assisting proteins in this process. Understanding how the protein folding process is assisted is important to understand not just the vital protein folding itself, but also the numerous pathologies, like Alzheimer's, that result from defective protein folding. To determine how protein folding and stability are determined in vivo, we have developed a strong genetic selection that directly links the stability of a protein to an easily selectable marker – antibiotic resistance. Using directed evolution, we are able to select on the one hand for variants of a target protein that are thermodynamically or kinetically stabilized or, on the other hand, for folding factors that are especially suitable to enhance the expression of recombinant proteins. Another major project in the lab is the detailed in vitro characterization of the mechanism of the acid stress chaperone, HdeA, and the periplasmic chaperone Skp. This involves probing the conformation of the chaperones under various conditions, studying chaperone-substrate interactions, and the fate of substrate proteins following chaperone inactivation. Furthermore, we are experimentally evolving enzymes that are involved in the disulfide bond formation and isomerization in the model organism E. coli. We are using a multifaceted genetic, biophysical and structural approach to investigate protein folding, including techniques like cloning, site-directed and random mutagenesis, enzymatic assays, Western blots, spectroscopic techniques (including UV-vis absorbance, fluorescence, FRET and circular dichroism), rapid mixing (stopped flow), protein purification and other. Internship: at least 3 months, $900/month Diploma/master thesis: >6 months, $1400/month PhD thesis: 3 years, $2100/month