The Scientist - USA (2019-12)

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S

uccess for physicians and bio-

medical researchers in repair-

ing birth defects, inducing the

regrowth of complex organs, normal-

izing cancer cells, and bioengineering

novel living machines will hinge on first

achieving a common goal: understand-

ing how cells collaborate to build and

rebuild large-scale anatomical struc-

tures. Over the past 20 years, research-

ers have made tremendous progress

in identifying specific genes necessary

for development, mostly by chronicl-

ing mutations or deletions of genes

that lead to the onset of diseases and

anatomical defects. But this informa-

tion is just the tip of the iceberg. While

the genome specifies the crucial “parts

list” for individual cells, researchers

have much to learn about the signaling

events that coordinate the collaborative

cellular processes to create and repair

complex anatomies.

In the post-genomic era, it is becom-

ing clear that the next step beyond iden-

tifying the genetically specified hardware

of the body involves understanding the

physiological software: the mechanisms

that enable cells and tissues to make

decisions and implement swarm dynam-

ics that remodel organ-level structure.

Often, the same anatomical outcome can

arise from a range of diverse starting con-

ditions. For example, normal frog faces

can arise even when tadpole faces have

their craniofacial tissues in scrambled

positions (Development, 146:dev.175893,

2019). To understand this anatomical

convergence toward the correct target

morphology, researchers must incorpo-

rate the deep insights of physics and com-

puter science into cell and developmen-

tal biology and remember that evolution

exploits physical forces such as biome-

chanics and bioelectrics.

The Allen Discovery Center at Tufts

University was founded in 2016, with

funding from Microsoft cofounder

Paul Allen earmarked for research into

areas he called the “Dark Matter of

Biology”—frontiers of interdisciplinary

biosciences that were as-yet unexplored.

There, we work to identify new scien-

tific hypotheses (for example, the idea

that anatomical goals are represented

by biophysical “memories” in tissues)

and experimental tools that will reveal

entirely new areas of life science. The

dynamic control of biological shape is a

problem that requires cross-disciplinary

collaboration and the synthesis of data

from an array of model systems. We and

our colleagues at the Allen Discovery

Center and beyond address this problem

from different perspectives and at differ-

ent levels of organization, ranging from

individual ion channels and bacterial

signaling to the much larger scales of

limb regeneration in the axolotl and the

control of whole-body axis patterning in

planaria and frog embryos.

Recent advances in the field have

revealed new ways to exploit endog-

enous bioelectric and neurotransmit-

ter control systems in neurons and in

other cells. For example, we found that

Cracking the Morphogenetic Code

Insights into non-neural bioelectricity are helping researchers understand

organismal growth and form.

BY JOSHUA FINKELSTEIN, KELLY McLAUGHLIN, AND MICHAEL LEVIN

CRITIC AT LARGE

While the genome specifi es

the crucial “parts list” for

individual cells, researchers

have much to learn about the

signaling events that coordi-

nate the collaborative cellu-

lar processes to create and

repair complex anatomies.