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

我的研究重点是营养、生殖和衰老之间的联系。营养的可获得性对有机体的生长和繁殖能力有重大影响，还会影响以衰老为特征的细胞和组织退化的进程。进化上保守的信号通路--从蠕虫到人类--检测营养水平，并将信息传递到全身，以协调整个系统的反应。例如，这允许动物在营养丰富的情况下生长和繁殖，而在营养较少的情况下，能量资源可能会转而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学功能，这些营养感应信号通路也控制着衰老过程中的变化速度。我的研究计划的主要目标是研究营养和营养反应信号通路如何控制寿命、繁殖和能量平衡。在接下来的五年里，我和我的研究小组将在我之前研究的基础上再接再厉，以实现三个短期目标。首先，我们将寻求确定营养水平过高(在这种情况下，葡萄糖过剩)是如何对生殖功能和卵细胞质量随年龄保持的负面影响的。在营养可获得性光谱的另一端，限制接触食物可以延缓随着年龄增长而出现的生殖能力下降，并导致寿命的大幅延长。我们的第二个目标是描述一种信号通路，它可能有助于控制这些对养分供应减少的反应。最后，我们将描述特定组织中因营养水平变化而发生的基因变化。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与年龄相关的变化。我们将使用线虫来解决这些问题，线虫是一种微小的蛔虫，是研究基本生物学问题的强大模型。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，这将是多个研究领域(例如，衰老生物学、生殖生物学、细胞间信号传递)的兴趣所在。由于许多受营养水平调控的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。

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.