PhD Student (gn*) Physiological Chemistry and Pathobiochemistry

Generate collagenase-sensitive probes whose cleavage site depends on native triple-helical conformation of collagen Equip these collagenase-sensitive probes with FRET (Förster resonance energy transfer)- and FLIM (fluorescence life time microscopy)-capable molecular moieties, which enable fluorescence-based real-time monitoring of their cleavage Determine characteristic features of the probes, such as thermal stability of the triple-helical conformation as well as affinity and selectivity for different proteases (e.g. collagenolytic and gelatinolytic matrix metalloproteinases (MMPs) and snake venom metalloproteinases (SVMPs) Use the probes to localize and quantify collagenase activity in damaged tissue (tissue samples of snake bites and other skin wounds by zymography) Use the probes to assess the inhibition of collagenase-targeting tools on different collagenases Develop non-cleavable homologs of the collagenase-sensitive probes that block the active site of collagenases EXPECTED RESULTS: Develop novel, diagnostic tools for mapping and quantifying collagenase activity within wounded tissue A test to determine collagenase activity as a marker of (aberrant) wound healing This