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

为什么我们会变老这个根本问题一直困扰着人类数千年。广泛接受的衰老进化理论假设衰老是生物体的结果？在不断变化的环境条件下，普遍需要协调生存和繁殖。然而，动物如何根据环境输入改变其生理机能仍不清楚。线虫是解决这个问题的绝佳模式生物，因为它的寿命很短，并且具有相对容易操作的基因组。该项目将研究转甲状腺素蛋白家族的一个成员 TTR-1，其功能未知，但已知会影响线虫的寿命。这项工作将在日本名古屋大学秀丽隐杆线虫细胞信号传导专家 Kunihiro Matsumoto 的实验室中进行。该项目将为一个几乎未表征的基因家族的功能提供新的见解，并增进对应激反应和衰老的生殖控制的了解。体细胞的繁殖和维持之间的权衡是生物体生理学的一个普遍特征，反映了能量分配的选择并影响抗压性和寿命。生物体如何协调环境输入、新陈代谢、应激反应和繁殖之间复杂的相互作用仍不清楚。线虫类转甲状腺素蛋白 (ttr) 基因家族的成员已被证明能够对压力做出反应并影响寿命，但这些蛋白质在线虫生理学中的实际作用仍然难以捉摸。虽然人们对线虫中的 ttrs 知之甚少，但单一脊椎动物运甲状腺素蛋白是亲脂性维生素和激素的载体。该项目将通过评估 TTR-1 可以在体外结合的脂质类型来研究一种 ttr（TTR-1）的功能。该项目将揭示一个功能未知的基因家族及其在激素信号传导应激反应和寿命整合中的潜在作用。该奖项属于东亚和太平洋地区暑期学院计划，支持美国研究生的暑期研究，由美国国家科学基金会和日本科学振兴会共同资助。

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.