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

我们为什么会变老这个基本问题已经困扰了人类几千年。被广泛接受的衰老进化理论假设衰老是由生物体引起的。在不断变化的环境条件下协调生存和繁殖的普遍需要。然而，动物如何根据环境输入来改变它们的生理机能仍不清楚。蛔虫秀丽隐杆线虫是解决这个问题的一个极好的模式生物，因为它寿命短，并且具有相对容易操纵的基因组。该项目将研究转甲状腺素样蛋白家族的一种成员TTR-1，它的功能未知，但已知会影响秀丽隐杆线虫的寿命。这项工作将在日本名古屋大学的松本国弘（Kunihiro Matsumoto）实验室进行，松本国弘是秀丽隐杆线虫的细胞信号专家。该项目将为一个几乎没有特征的基因家族的功能提供新的见解，并推进对应激反应和衰老的生殖控制的认识。生殖和维持体细胞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，并影响了抗逆性和寿命。生物体如何协调环境输入、代谢、应激反应和繁殖之间复杂的相互作用仍不清楚。秀丽隐杆线虫（C. elegans）的转甲状腺素样（ttr）基因家族成员已被证明对应激作出反应并影响寿命，但这些蛋白质在蠕虫生理中的实际作用仍不清楚。虽然我们对秀丽隐杆线虫中的促甲状腺素知之甚少，但单一脊椎动物的促甲状腺素是亲脂性维生素和激素的载体。该项目将通过评估ttr -1在体外可以结合哪种类型的脂质来研究ttr -1的功能。该项目将揭示一个未知功能的基因家族及其通过激素信号在应激反应和寿命整合中的潜在作用。该奖项隶属于东亚和太平洋暑期研究所项目，由美国国家科学基金会和日本科学促进会共同资助，支持一名美国研究生进行暑期研究。

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.