1. AntiSec Antibacterials
We are collaborating with Pfizer Inc. (Groton, USA) in the development of novel Sec antibacterials.
2. Protein secretion biotechnology
We wish to develop technologies for the expression/secretion/purification of human polypeptides in bacteria (collaboration with J.Anne, Louvain and A.Tsiftsoglou,Thessaloniki). One of the major contributions to the cost of heterologous biopharmaceuticals is the labour-intensive process of protein purification and the denaturation/refolding frequently required. A possible route to overcoming this problem could be the expression of proteins of interest as secreted polypeptides in bacteria. We have now expressed ~10 polypeptides (e.g. interferon g, TNFa, interleukins etc.). Most of these have been expressed either in Streptomyces lividans or E.coli (Pozidis et al., 2001). S.lividans is a Gram positive bacterium (i.e missing an outer membrane) and therefore the proteins that it secretes are releases directly into the medium facilitating recovery. Moreover, a huge body of data is available on the use of this bacterium in large-scale fermentations due to its capacity to produce antibiotics.Technologies and products developed in our lab are transferred and marketed by MINOTECHbiotechnology.
Other recombinant proteins of interest include membrane-embedded proteins such as GPCRs and ion channels as well as proteins isolated after screening of microbial metagenomes such as a novel xyloglucanase (Sianidis et al., 2005) and a novel glycosyltransferase involved in aranciamycin biosynthesis (Sianidis et al., 2006). Using systems biology tools we are involved in the development of optimised heterologous secretion of biopharmaceuticals from bacteria. This work is part of the EU project Streptomics.
Technologies for the reconstitution of membrane proteins into lipid bilayers can be used for the development of specific biosensors. These can be used to study membrane protein receptors with their respective ligands. Optical, acoustic(collaboration with E.Gizelli, UoC Biology and IMBB) and fluorescence-based biosensors are being developed. In addition we are developing a novel FRET-based glucose biosensor that will be part of an integrated platform that includes an implantable monitoring system and telemonitoring modules for diabetes patients (Shenkman et al, 2007). This work is part of the P.Cezzane EU network.
4. Bionanotechnology of transport devices and motors.
Using optical biosensor, fluorescence and surface polymer technologies. We are interested in exploiting the motor-like ATPases and the tube-like structures of the Sec and T3S systems in the development of novel bionanomachines.