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

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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.