NSF Award
2426394
Animals of all species face a challenging problem: they must be resilient to changes in environmental temperature that alter the functional properties of all of their proteins. This general problem has become even more significant in the face of climate change, in which many species are seeing temperatures in the world that are more extreme than those to which they are accustomed. This study combines computational and experimental methods to study the effects of temperature on the feeding system in the nematode worm, C. elegans. As part of the feeding apparatus, the pharynx of C. elegans functions as a rhythmic pump, which is in turn activated by a rhythmic circuit. An intriguing set of observations has suggested a very unconventional biophysical mechanism underlying the activation of this circuit, which may provide clues to a new mechanism that ensures its robustness to temperature changes and noise. Understanding all of the myriad mechanisms that animals have evolved to ensure their resilience to the fluctuations in their natural environments will be important for understanding how and when different animal species will be significantly compromised by global warming. The project includes opportunities for trainees from minoritized groups to participate in research in an interdisciplinary environment, and the development of a module on thermal tolerance for the Acton, MA, Science Discovery Museum and a travelling science exhibit for the public.<br/><br/>The overall goals of this proposal are to define the neuronal and circuit principles that underlie functional resilience to temperature using an invertebrate organism that is facing constantly changing temperatures in the wild. The investigators propose to combine experimental analyses and theoretical modeling to determine resilience and failure modes in the pharyngeal pumping rhythm of C. elegans to temperature changes. In experimental studies, the investigators will first obtain quantitative measures of the effects of temperature on the pumping rhythm. Then, they will establish how temperature resilience in this rhythm is influenced by the presence or absence of excitatory and inhibitory neuronal inputs into the pharyngeal muscle, as well as by neuromodulation. They also will determine whether there is natural variation in the temperature resilience of the pumping rhythm across wild C. elegans strains, and whether this resilience correlates with natural variation in thermotolerance. In modeling studies, the investigators will use the experimental work as a foundation to construct computational models with temperature-sensitive conductances and characterize their temperature resilience. The investigators will include models of how the resilience range is altered by excitatory and inhibitory inputs and neuromodulatory currents. They will perform these analyses using a recently implemented model of the pharyngeal pumping circuit and a set of degenerate models. The investigators expect that experimental data will inform and constrain the modeling work, and that the theoretical models will in turn allow experimental testing of predictions. Findings from this interdisciplinary work are expected to provide new information regarding mechanisms of neuronal resilience to climate change.<br/><br/>This project is supported jointly by Division of Integrative Organismal Systems in the Directorate for Biological Sciences of NSF and the Kavli Foundation.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
