Protein Biotechnology

Recombinant DNA technology allows proteins to be engineered to suit our needs. From ELISA to Biosensors, many applications require hydrophilic proteins to be attached to hydrophobic man-made surfaces like plastic overcoming coatability and binding problems. Similar challenges such as adhesion and nutrient uptake at the membrane-aqueous interface in bacteria have forced them to evolve a simple solution. Pioneering work done by Dr. Sankaran in association with Prof. Henry C. Wu, USA showed in E.coli and other bacteria that a three-enzyme pathway attaches a lipid adapter to the N-terminus of hydrophilic proteins. This helps to anchor such lipoproteins to the membrane.

Prof. Sankaran's group has exploited this machinery of E.coli, a popular host for expressing recombinant proteins, for successful lipid modification of experimental proteins. In an indigenous technology development the success of such models is now being extended to a variety of commercial applications including ELISA, biosensors and drug delivery. This work was partly funded by AICTE, India.

In another important application, as lipid modification is essential, unique to and ubiquitous in bacteria, it is also a target for broad-spectrum antibiotics. High throughput assays for the biosynthetic enzymes to screen for new antibiotic molecules and downstream processing protocols are being developed in collaboration Prof. Paul D. Rick, USA. In a major bioinformatic exercise, taking advantage of his vast first-hand knowledge on this subject, Sankaran and Madan Babu have launched a website for bacterial lipoproteins.

Molecular pathogenesis and early diagnosis of Diarrhoeal pathogens Childhood diarrhoea is one of the root causes of poverty and socio-economic problems in developing countries. Nearly 50% of infantile mortality, malnutrition and poor physical and low IQ are due to bloody and persistent diarrhoea caused by Shigella and E. coli. Availability of simple, rapid and low-cost but sensitive early diagnostic methods designed for peripheral clinical labs operating with minimum facility will drastically reduce this burden in bulk of the affected population living in poor sanitary conditions. His discovery of a unique periplasmic enzyme activity in Shigella (FEBS Lett. 512, pp8, 2002) has become an attractive diagnostic candidate with the above attributes. The diagnostic kit is being developed in collaboration with Prof. Peter Williams, UK and other collaborators as part of the European Commission's project.

Based on detailed molecular pathogenesis studies appropriate diagnostic targets are being identified in a variety of E.coli pathogens and this work is being supported by the Departmental Special Assistance programme of UGC and Indo-French collaboration with Dr. Eric Oswald. Ultimately the aim is to develop an integrated diagnostic tool that'll detect potentially dangerous enteropathogens at early stages of childhood diarrhoea and help to start effective antibiotic therapy without delay.