What is sleep and how do we study it?
Every animal on earth sleeps and humans spend greater than a third of their lives doing it. Amazingly, fundamental questions about sleep remain unanswered including: What is its function? And; How is it regulated at a molecular and genetic level? In fact, sleep remains one of nature’s greatest biological mysteries! However, it has become clear that sleep is evolutionarily ancient and conserved at the genetic level.
Simple “model organisms” have become powerful tools for exploring sleep because many of the same genes and molecules that drive their biology also controls ours. The nematode Caenorhabditis elegans is a microscopic, free-living worm that has been widely used in the lab as a model for understanding development and behavior. C.elegans displays sleep behaviors at regularly timed intervals during larval development and in response to stressful environmental stimuli.
Sleep Neurons
Why C. elegans?
But, why study sleep in a microscopic worm? First, C.elegans are a powerful genetic system that we can manipulate with ease. They are transparent and grow from an embryo to an adult in 4 days, thus allowing for fast genetic alteration and experimentation. Because of their simplicity, we know the location of every one of their cells and the connection of every neuron in its simple nervous system (Only 302 neurons!). The Nelson Lab takes advantage of this amazing animal in hopes to further our understanding of sleep. Specifically, our research focuses on the identification of sleep regulating neurons and how they communicate as neural circuits to control sleep behavior and the characterization of the mechanisms of how signaling molecules called neuropeptides regulate sleep. We use a combination of techniques from the disciplines of genetics, molecular biology, neurobiology and behavior.
Research Projects
Genetic and Molecular Regulation of Sleep
Our lab leverages powerful genetic tools, such as CRISPR, optogenetics, and calcium imaging, to study sleep regulation with single cell resolution. Our goal is to understand how cells communicate and coordinate sleep and arousal. Our primary focus has been characterizing neuropeptide signaling.
Optogenetic and Biosensor Tools
We have helped implement genetic tools for behavioral research in C. elegans and have been using these to explore the mechanisms of sleep. Some examples include the red light-activated adenylyl cyclase (IlaC22) and an AMPK FRET-based biosensor (AMPKAR-EV).
Cellular Effects of Sleep Deprivation
We are interested in better understanding how sleep deprivation alters fundamental cellular processes such as transcription/translation and metabolic energetics. To do this we use fluorescent imaging of cellular components and pathways following genetic sleep disruptions.
Science Outreach
Our lab is dedicated to expanding access to STEM-related research within the Philadelphia community. We are establishing an outreach project that will allow for participating Philadelphia public schools to participate in C. elegans sleep research remotely; we call it Worm-Cam.
C. elegans in action
Waking a sleeping worm (See Nelson et al. 2014)
Lab Announcements
