Ming Hammond

​Exploiting riboswitches to study and manipulate bacterial signaling

Bacteria are both our friend and foe. They reside on our bodies and are ubiquitous in both natural and manmade environments. Through signaling pathways, individual bacteria respond to environmental conditions and interact with neighboring cells, which can include host cells as well as other members of the microbial fauna. Thus, the study of bacterial signaling is important for understanding both pathogenesis that leads to infectious disease and maintenance of the microbiota that promotes human health.

The long-term goals of my research program are to understand how bacterial species adapt to complex environments and communicate with neighboring cells, and to develop compounds for selectively targeting bacterial lineages to manipulate microbiota composition. Our general strategy toward both of these goals involves exploiting natural RNA-based receptors called riboswitches that regulate bacterial genes in response to small molecule ligands. Toward the first goal of studying bacterial signaling, we are using the ligand recognition domains of riboswitches to develop fluorescent biosensors for real-time cellular imaging of cyclic dinucleotides, which are a newly expanded class of second messengers. RNA-based fluorescent biosensors offer advantages for economical synthesis, rapid design-test-build cycles, and access to biosensors when protein receptors are unavailable or not amenable. Toward the second goal of manipulating microbiota composition, we are targeting riboswitches found only in certain bacteria to impede cell growth in a lineage-specific manner. Unlike most RNAs, riboswitches form a well-defined ligand binding pocket that is a suitable target for small molecule modulators.