Pincus Lab

Washington University School of Medicine

Department of Developmental Biology
and Department of Genetics

We study individual variability, aging, and robustness.

From human twins to the products of division of a single bacterium, genetically identical organisms often develop into very different individuals and experience different life histories, even in identical environments. Such differences, and other instances of so-called non-genetic individuality, are the focus of the Pincus lab.

We primarily use variability in C. elegans lifespan as a metazoan model for understanding noise control, homeostatic robustness, and biological individuality. Overall, we hope to understand why and how some individuals age more successfully than others.

The Origins of Individuality

Our fundamental goal is to understand variability in living systems: what are the origins of biological individuality? How are individual differences determined, limited, and exploited by a species?

On the one hand, we are interested in the origin of homeostatic robustness: how do organisms control biological noise and maintain their state over time? On the other hand, a certain degree of variability may be adaptive in an unknown and ever-changing environment.

Living organisms have to carefully manage this trade-off between stability and adaptability, and we want to understand how.

Variability in Lifespan

In particular, we explore individual differences in lifespan and the rate of aging as an exciting and clinically important case study for these broad biological questions. Aging is intimately related to the maintenance (and loss) of robustness, and is a trait in which there is a large amount of individual differences.

Even C. elegans, with their famously invariant pattern of embryonic development, experience large differences in individual lifespans. Raised in identical lab environments, genetically identical C. elegans show as much relative variability around their two-week lifespans as humans do around theirs of eighty years. We hope to learn why this is, what more-robust individuals have that their frailer siblings lack, and what that means for human health and aging.