What was not known until recently is a crucial missing link in the network in each bacterium that results in the ability to change behavior. Just before he came to Virginia Tech in August 2004, Kulkarni and his collaborators at Princeton solved the mystery. Using bioinformatics and modeling, Kulkarni drafted theoretical predictions for the missing regulatory element, which were confirmed experimentally by his colleagues at Princeton.
"We showed that the crucial missing element was a group of genes called small RNAs. ("The small RNA chaperone Hfq and multiple small RNAs control quorum sensing in Vibrio harveyi and Vibrio cholerae," by D.H. Lenz, K.C. Mok, B.N. Lilley, R.V. Kulkarni, N.S. Wingreen, and B.L. Bassler, published in Cell, July 9, 2004). "As it turns out, quorum sensing is a hot topic in biology, and small RNAs is another hot topic. The convergence of these topics is exciting, and it has resulted in several additional questions," Kulkarni said.
He will address these questions in his Powe-funded research. "We are asking, what are the environmental signals, apart from quorum sensing, that are integrated by the small RNAs to initiate changes in behavior. An example might be the amount of nutrients in the environment. Another question is why are there multiple RNAs? The sensing and communication circuit functions even if some of the RNAs are removed ?in fact, even if there is only one small RNA. Modeling the circuit will be crucial in understanding how it functions and integrates signals from multiple inputs," Kulkarni said.
A third question is how the circuit regulates important biological processes, such as biofilm formation and virulence. "Biofilms make bacteria resistant to antibiotics, so preventing t