Mechanistic insights into nutrient availability responses, from molecular changes to whole-body effects

从分子变化到全身效应，深入了解营养物质可用性反应的机制

• 批准号: RGPIN-2022-05149
• 负责人: Templeman, Nicole
• 金额: $ 2.4万
• 依托单位: University of Victoria
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=745912
• 关键词: Mechanistic; insights; into; nutrient; availability

My research focuses on the ties between nutrients, reproduction, and aging. The availability of nutrients has significant repercussions for an organism's ability to grow and reproduce, and also affects the progression of cell and tissue deterioration that characterizes aging. Signaling pathways that are evolutionarily conserved-from worms to humans-detect nutrient levels, and convey that information throughout the body to coordinate systems-wide responses. This allows an animal to grow and reproduce when nutrients are plentiful, for instance, whereas with fewer nutrients, energetic resources may instead be devoted to processes such as maintaining cell quality and tissue integrity. Through their regulation of crucial biological functions, these nutrient-sensing signaling pathways also govern the rate of changes during aging. The broad goal of my research program is to study how nutrients and nutrient-responsive signaling pathways control lifespan, reproduction, and energy balance. In the next five years, my research group and I will build on the foundations laid in my previous research to meet three short-term objectives. First, we will seek to determine how excessive levels of nutrients (in this case, a surplus of glucose) cause negative repercussions for reproductive function and the maintenance of egg cell quality with age. At the other end of the nutrient availability spectrum, restricting exposure to food can delay the decline in the reproductive capacity that takes place with age, and cause a dramatic extension of lifespan. Our second objective is to characterize a signaling pathway that may be instrumental in governing these responses to decreased nutrient availability. Lastly, we will characterize the genetic changes that take place in specific tissues in response to changed nutrient levels. This research will be conducted by undergraduate and graduate students who will use genetics, physiology, cell biology, and molecular biology techniques to study age-related changes spanning from the molecular and cellular levels to the whole body. We will address these questions using C. elegans, which is a tiny roundworm that is a powerful model for studying basic biological questions. Ultimately, this work will allow us to discover new regulators of cell, tissue, and whole-body changes during aging, which will be of interest for multiple areas of study (e.g., aging biology, reproductive biology, inter-cellular signaling). Since many of the signaling pathways and mechanisms regulated by nutrient levels are closely similar across diverse species, we anticipate that these experiments will provide compelling insights into evolutionarily conserved processes responsible for controlling growth, reproduction, and aging.

我的研究重点是营养、繁殖和衰老之间的联系。营养素的可用性对生物体的生长和繁殖能力有重大影响，也影响细胞和组织退化的进展，这是衰老的特征。从蠕虫到人类，进化上保守的信号通路检测营养水平，并将信息传达到整个身体，以协调整个系统的反应。例如，这使得动物在营养丰富的情况下能够生长和繁殖，而在营养较少的情况下，能量资源可以用于维持细胞质量和组织完整性等过程。通过调节关键的生物功能，这些营养传感信号通路也控制着衰老过程中的变化率。我的研究计划的广泛目标是研究营养和营养反应信号通路如何控制寿命，生殖和能量平衡。在未来五年，我和我的研究小组将在我以前研究的基础上，实现三个短期目标。首先，我们将试图确定过量的营养物质（在这种情况下，葡萄糖过剩）如何对生殖功能和随着年龄的增长维持卵细胞质量造成负面影响。在营养素供应范围的另一端，限制对食物的接触可以延缓随着年龄的增长而发生的生殖能力下降，并导致寿命的显著延长。我们的第二个目标是表征一个信号通路，这可能有助于管理这些反应，减少养分供应。最后，我们将描述特定组织中发生的遗传变化，以应对营养水平的变化。这项研究将由本科生和研究生进行，他们将使用遗传学，生理学，细胞生物学和分子生物学技术来研究从分子和细胞水平到全身的年龄相关变化。我们将使用C来解决这些问题。它是一种微小的蛔虫，是研究基本生物学问题的有力模型。最终，这项工作将使我们能够发现衰老过程中细胞、组织和全身变化的新调节因子，这将对多个研究领域（例如，衰老生物学、生殖生物学、细胞间信号传导）。由于营养水平调节的许多信号通路和机制在不同物种中非常相似，我们预计这些实验将为控制生长，繁殖和衰老的进化保守过程提供令人信服的见解。