Principal Investigator (PI): Dr Patrik Samuelson

Description: Microbial host strains are attractive for production of recombinant proteins. Attempts to produce complicated proteins in bacteria, for human therapeutic use, however, often result in misfolded biologically inactive proteins or insoluble protein aggregates. The underlying reasons to this may, among other things, be that bacteria lack the proper folding machinery for the protein of interest. Therefore, we seek to engineer bacterial strains that are better equipped to deal with such shortcomings. Avenues that we will explore are; (i) introduction of new chaperones and/or foldases, (ii) directed evolution of specific folding modulators, (iii) and genetic engineering of the host.

Site-specific proteolysis has a profound role in the regulatory mechanism of many biological processes. Moreover, it is also critical in the replicative cycle of many viruses and also seems to play a role in the development of certain other disease conditions. Besides these biological effects, site-specific proteases may also find use as a tool for removal of affinity tags from fusion proteins. To date, few site-specific proteases have been isolated although many general proteases are known. Consequently, there is a need for simple and convenient systems that could aid in the isolation of novel site-specific proteases. We are currently developing novel selection/screening systems for isolation of site-specific proteases. These systems are then used in order to (i) isolate novel site-specific proteases, (ii) change the substrate specificity of proteases, and (iii) search for novel protease inhibitors.