EAPSI: Investigating the role of a Putative Lipid-Binding Protein in Hormonal Signaling and Control of Lifespan in the Worm C. Elegans

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The fundamental question of why we grow old has puzzled humans for thousands of years. Widely-accepted evolutionary theories of aging have postulated that aging results from organisms? universal need to reconcile survival and reproduction under changing environmental conditions. However, how animals modify their physiology according to environmental inputs remains unclear. The roundworm C. elegans is an excellent model organism in which to address this question, as it is short-lived and has a genome that can be relatively easily manipulated. The project will investigate a member of the transthyretin-like protein family, TTR-1, which has an unknown function, but is known to affect lifespan in C. elegans. This work will be conducted at Nagoya University in Japan, in the lab of Kunihiro Matsumoto, an expert in cellular signaling in C. elegans. The project will provide new insights into the functions of a virtually uncharacterized gene family and advance knowledge of reproductive control of stress responses and aging. Trade-offs between reproduction and maintenance of the soma are a general feature of organismal physiology reflecting choices in energy allocation and affecting stress resistance and lifespan. How organisms coordinate the complex interplay between environmental inputs, metabolism, stress response, and reproduction remains unclear. Members of the transthyretin-like (ttr) gene family of the nematode C. elegans have been shown to respond to stress and affect lifespan, but the actual roles of these proteins in worm physiology remain elusive. While little is known about ttrs in C. elegans, the single vertebrate transthyretin is a carrier of lipophilic vitamins and hormones. The project will investigate the function of one ttr, TTR-1, by evaluating which types of lipids TTR-1 can bind in vitro. The project will shed light on a gene family of unknown function and its potential role in integration of stress response and lifespan by hormonal signaling. This award under the East Asia and Pacific Summer Institutes program supports summer research by a U.S. graduate student and is jointly funded by NSF and the Japan Society for the Promotion of Science.