The Mendenhall lab is working to alleviate age-related disease and suffering by studying individual cells in live animals during the course of aging. What keeps the cells of particularly long-lived, healthy individuals functional for longer amounts of time? This question is particularly striking when considering that genetically identical humans (monozygotic twins) live for different amounts of time and succumb to different diseases. Even in well-controlled laboratory environments, genetically identical animals live for different amounts of time.
Dr. Mendenhall’s laboratory uses the nematode C. elegans to understand how and why genetically identical populations of cells and animals in the same environment do different things, specifically how much and what kind of physiological variation is intrinsic/stochastic, programmed, and heritable. Ultimately, they want to know how physiological variation that manifests between genetically identical cells in genetically identical animals affects the aging process.
This lab directly observes events inside living cells. They study the causes and consequences of variation in gene expression and differences in cell physiology by using a spectral confocal microscope to measure the physiological properties of individual cells. Many of the different physiological states they observe in single cells may be consequential. Some of these physiological states must be identified by observing multiple processes operating in individual cells, often by observing multiple, single-copy reporter genes or ‘knock-in’ fusions of fluorescent proteins to native genes.
Thus, the Mendenhall lab uses an array of reporter genes to identify cellular mechanisms that may cause variation in lifespan by measuring the functionality of different cellular subsystems during the course of aging. They are generating a cell-resolution atlas of age-related changes in gene expression and other kinds of cell physiology. These data are used to generate and test hypotheses to determine mechanisms of cell, organ and organism failure during the natural aging process, and in different disease models, including C. elegans models of cancer (mutated Ras gain of function signaling) and Alzheimer’s disease.