Protein folding is a long-standing biological problem. The discovery of parallel folding and unfolding pathways highlighted that single molecule techniques are required to uncover how proteins fold. As a graduate student in Professor Daniel J. Müller's lab in Dresden, we have developed a mechanical single molecule approach where forces generated by atomic force microscopy (AFM) play the role of the denaturant and probe the stability of individual proteins. I was able to measure the energy stabilizing helices in the prototypical membrane protein bacteriorhodopsin (Janovjak et al. 2004, Structure 12:871ff) and provided an experimental measure of roughness in the protein’s energy landscape (Janovjak et al. 2007, J. Am. Chem. Soc. 129:246ff). We also conducted the first combined thermal and mechanical unfolding experiment (Janovjak et al. 2003, EMBO J. 19:5220ff) and, through instrumentation development, probed protein visco-elastics (Janovjak et al. 2005, Biophys. J. 88:1423ff) and extended the dynamic range of the technique (Janovjak et al. 2005, Eur. Biophys. J. 34:91ff). Finally, we were able to directly follow single membrane proteins as they proceeded through the folding process (Kedrov et al. 2006, J. Mol. Biol. 355:2ff). This work provided detailed insights into the otherwise inaccessible energetics underlying the stability and heterogeneous folding pathways of membrane proteins.

To complement our mechanical single molecule experiments with computer simulations, I started a collaboration with Professor Marek Cieplak (Polish Academy of Sciences, Warsaw), who is an expert in molecular dynamics simulations of protein mechanics. In 2006, our work yielded the first theoretical study of mechanical unfolding of a membrane protein (Cieplak et al. 2006, BBA Biomembr. 1758:537ff) and it included the first independent confirmation of unfolding pathways that we proposed earlier based on experimental data. More recently, our collaboration focused on modeling dynamic protein stability using molecular dynamics and kinetic models. In early 2009, Dr. Piotr Szymczak from Warsaw and I published the first manuscript to describe the effect of a repetitive, time-dependent force on a folded protein structure (Szymczak and Janovjak 2009, J. Mol. Biol. 390:443ff), which we consider a fundamental step towards understanding protein mechanics under complex forces such as during mechano-signaling.

How can we control nerve cell activity using light?

Light-controlled systems provide many advantages for manipulating biological function in vitro and in vivo through high spatio-temporal resolution and precise control of signal strength. In particular, genetically-targeted, light-activated ion channels can control activity in specific nerve cells and thereby probe neuronal circuits. As post-doc with Professor Udi Isacoff and in collaboration with Professor Dirk Trauner (Ludwig-Maximilians-Universität, Munich), we have built ion channels that are gated by photochromic tethered ligands. Using chimeric re-design of a glutamate receptor, we developed a potassium-selective ion channel that is light-activated (Janovjak et al. 2009, manuscript submitted). When expressed in neuronal cells and activated by a brief light pulse, this ion channel reversibly and completely inhibits action potential firing (Janovjak et al. 2009, manuscript submitted). We also devised a Monte-Carlo approach to rapidly and rationally design light-gated systems (Janovjak et al. 2009, manuscript in preparation). Our simulations both explain the functionality of existing light-gated proteins and allow the design of novel light-gated ion channels and G-protein coupled receptors.

You can download an online version of my CV here.