Exploring the fitness landscapes of riboswitches

Riboswitches are mRNA portions fold into specific structures to regulate many essential bacterial processes. Furthermore because riboswitches are only present in bacteria, they are also important therapeutic targets for novel antibiotics. We are curious about what benefit riboswitches confer upon their host organisms, and how robust they are to changes (mutations). To answer these questions we are exploring the fitness landscapes of riboswitches. A fitness landscape is a description of how individual sequences from a pool of potential sequences perform a specific function. To characterize the fitness landscape of riboswitches we use both computational and laboratory tools to examine large numbers of sequences and assess whether they fold into the correct shape, or retain the original biological function. Computational modeling of existing natural sequences and their mutants allows us to predict a fitness landscape. Experimental testing in the laboratory allows us to directly test hypotheses generated from computational approaches and determine which sequences retain the biological function. By understanding how important riboswitches are for the organism, and how mutations impact riboswitch structure and function, we expect to identify which riboswitches are likely to make the most effective therapeutic targets.