Scientists at Rice University have developed a technique to dial up or down the sensitivity of two-component systems, which are an important source of sensors for synthetic biology. The team says its technique could enable the engineering of tailor-made biosensors in the development of diagnostic gut bacteria, detection of environmental pollutants, or automated control of nutrient levels in soil.
While these sensors have been known for three decades, they weren't sensitive enough, according to Jeffrey Tabor, a synthetic biologist at Rice. He and Rice alumnus and lead author Brian Landry set out to decrease the amount of input needed to turn them on. In a paper published yesterday in Nature Communications, they described how phosphatase activity can have a dramatic effect on the detection thresholds of two-component systems.
Previous research had shown that mutations to the first component, a signaling sensor protein known as a histidine kinase, can be used to control the extent of phosphorylation of the second component, a response regulator protein. Landry worked with co-author Lucas Hartsough to identify a "hot spot" amino acid present in 64% of all sensor histidine kinases that can be mutated to tune sensitivity.
Two-component systems can be triggered by many kinds of inputs, including gases, heme molecules in blood, sugars, gut polysaccharides, human or plant hormones or even light. "That's why we're so excited about this," Tabor said. "These sensors all operate the same way. They all have the phosphatase and the kinase. We've identified over 25,000 of them in bacterial genomes and we think our strategy will work on most of them."