How does an organism, as a whole, overcome physiological challenges?

Top-down view of a whole larval zebrafish, forebrain to spinal cord, with active cells highlighted.

The observability gap

Many of an organism’s capabilities do not reside in any single organ, but rather emerge from cellular interactions distributed across tissues. Yet existing methods either survey the whole body without resolving individual cells, or resolve cellular dynamics within a single region, or capture both but at a single moment — each providing only a sparse view of body-wide networks.

Extending neuroscience to the whole body

The lab takes a WHOLISTIC approach to studying state-dependent decision-making by extending the tools and approaches of neuroscience to the whole body. We develop and deploy technology to measure, probe and control cellular activity across the brain and body in transparent vertebrates (zebrafish and Danionella), and use dynamical systems modeling and machine learning to uncover principles by which cells compute and coordinate to meet physiological challenges.

Brain–body interactions and state transitions

We are particularly interested in the interplay of brain and body during organismal state transitions. One such example is sleep: sleep is defined in terms of neural activity, yet sleep deprivation disrupts many aspects of physiology — metabolism, immunity and cardiovascular function. Why? Imaging body-wide cellular activity lets us observe, for the first time, how such state transitions unfold across the organism, and dissect the brain–body circuits that underlie them.

Whole-body screening platform

We are also automating the platform to run whole-body drug screens at scale. Drugs act on the whole organism, yet most screens either report on a few cell types in a dish, which cannot predict off-target effects, or measure low-dimensional endpoints in an animal, which say little about mechanism and are thus hard to act on. We aim to fingerprint each compound by its evoked response function across organs to identify novel cellular properties, drug targets and pathways.

To read more about WHOLISTIC 1.0, head to wholistic.janelia.org.