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Research Overview

So much of our experience is visual, it can be surprising to learn that light controls widespread functions -- including the circadian rhythm, sleep, locomotion, and the pupillary light reflex -- without impinging on awareness. Rods and cones, long believed to be the only mammalian photoreceptors, are not required. 

This "non-image vision" is mediated largely by the intrinsically photosensitive retinal ganglion cells (ipRGCs), newly discovered photoreceptors that capture light with a pigment, melanopsin, and directly drive neurons in the retina and over a dozen brain regions. The widespread influence of non-image vision is reflected in the many diseases associated with its dysfunction. For instance, ipRGCs are the principal means of synchronizing the circadian clock with local time, and dysregulation of the clock has been implicated in poor mental health, metabolic disorders, cancer, and cardiovascular disease. 

Our overarching interest is how organisms regulate their behavior according to the environment. Non-image vision provides a rigorous paradigm for tracking an environmental signal all the way to motor output. The signal, ambient light, can be precisely matched for behaving animals and in vitro experiments. The intact circuitry of the retina is accessible with minimal perturbation. Non-image behaviors are readily measured, while their diversity allows investigation of signal processing across numerous brain regions. 

Importantly, ipRGCs are selectively manipulable through the melanopsin promoter, and the influence of ipRGCs on the whole animal can be isolated using established mouse models with rods and cones disabled. These features allow us to take a quantitative approach to understanding the system. We use electrophysiology and imaging on transgenic mice and tissues to connect biophysical mechanisms to behavior. 

About Michael Do

Michael Do received his PhD in Neurobiology from Harvard University, where he studied with Bruce P. Bean how neurons of the subthalamic nucleus generate rhythmic activity without any external influence. He then joined King-Wai Yau at the Johns Hopkins University School of Medicine to investigate newly discovered photoreceptors in the mammalian eye that are critical to "non-image" visual functions such as regulation of the circadian clock and of sleep. 

Dr. Do does basic research on biological mechanisms that are important to health and disease. He has been supported by fellowships from the Howard Hughes Medical Institute and National Eye Institute, and recognized by awards from the Johns Hopkins School of Medicine and Federation of American Societies for Experimental Biology.

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