Exploring Circadian Cycles in Intestinal Firmicutes

Cornell University, Ithaca NY

Investigators

Abstract

Most life on Earth follows a daily routine guided by predictable environmental cycles (light and dark, temperature changes etc.). Some aspects of the routine are controlled by external cues while some are maintained using circadian rhythms. These internal, self-sustained clocks with a periodicity of about 24 hours allow microbes, animals and plants to anticipate and prepare for daily fluctuations. Recently, self-regulated clocks composed of one or a few proteins have been discovered, suggesting that genes for a robust clock can be readily acquired. Thus far, true bacterial clockworks have been characterized only in phototrophs (that harvest energy from sunlight), but other bacteria would likely benefit from an internal clock. Specifically gut microbes, with a clock that allows them to anticipate changes in host activities, would have an advantage over bacteria without a clock. Shift workers often suffer intestinal discomfort and weight gain. Gut microbes out of sync with their human host may be contributing to these unwanted physiological changes. Uncovering a gut microbe circadian clock would inform targeted remedies to combat undesirable physiological changes that accompany our modern lifestyles. To date, the complexity of gut microbial communities and lack of any readout for daily processes have hampered the ability to observe regular functions in most gut microbes. To circumvent these issues, wild surgeonfish and their intestinal bacteria will be used as a natural model system to describe daily metabolic and developmental cycles. One group of Firmicutes, Epulopiscium spp. and related epulos, are naturally occurring, abundant intestinal symbionts that produce conspicuous internal offspring once every 24 hours in a predictable process. This provides a meter of everyday physiological changes in natural symbiont populations. Daily physicochemical changes in the intestinal ecosystem will be characterized to uncover regular fluctuations that may be used for entrainment. Symbiont oscillations will be determined by analyses of their temporal transcriptome and the cyclical redox cycle of a widely distributed clock protein. The project provides training opportunities for postdoctoral, graduate and undergraduate researchers. An undergraduate Reciprocal Exchange Program will be developed to build a cooperative learning group that will contribute to the research project while building networks and skills for advanced training. Native Pacific Islanders and other groups that are underrepresented in the sciences will be specifically recruited for these opportunities. Project results will uncover fundamental modes by which gut symbionts coordinate their activities with those of their host.