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Inside Salk 12 | 15

www.salk.edu

“Right now the spatial information of those cells

is very hard to quantify and measure,” Cang

says. He is also in talks with other potential

collaborators to use this technique to quantify

latent HIV genetic material inside cells, some-

thing that is currently hard to pinpoint.

A collaboration like this, adds Cang, wouldn’t

have happened anywhere else. “I don’t know

anyone who is pushing sequencing this far,”

he says. “You need someone with the biological

and technical experience like Manching and

the engineering background like me, and an

environment that supports doing something

risky but is also collaborative, like Salk.”

IMAGING THE UNSEEN

Salk Assistant Professor

Nicola Allen

wanted

to find the answer to the question: how many

neuronal connections are there in a developing

brain? While it’s easy enough to take a snapshot

of dyed brain cells, figuring out the number of

synapses—specialized connections that neurons

use to communicate—was a much bigger

computational problem, but one that could help

to understand how the brain develops and what

happens when things go awry.

She found a solution in a collaboration with

Michael Adams

, a Biophotonics Core staff scien-

tist and physicist. Adams developed a software

program to count the number of synaptic con-

nections in a volume of brain tissue. This work

will let the Allen lab ultimately investigate if

altering the function of other brain cells, known

as astrocytes, affects the formation of these

synapses in developing and mature brains.

“The Biophotonics Core helped us beyond what

we could do on our own,” says Allen, who has

used most of the Salk cores to advance her neu-

roscience research. “It’s not just about training

you on how to use a confocal microscope; the

core staff talks to you about your experiments

and their design to do science most effectively.”

Salk’s Biophotonics Core was founded in 2011

as part of the Waitt Advanced Biophotonics

Center, which was established with a $20 mil-

lion gift from the Waitt Foundation. With a staff

of only a few, this core remains one of the most

heavily used shared resources at the Institute.

About 40 labs rely on the two dozen state-of-

the-art imaging platforms it houses, including

Michael Adams and Nicola Allen

Brain cells called astrocytes are pictured

in red, neuronal nuclei in blue.

Courtesy of the Allen lab

cell,” says Cang, who was awarded a Waitt

Advanced Biophotonics Imaging Tools and

Technologies Seed Grant to pursue this work.

“We want to be able to put the entire tissue

onto a flow cell, amplify the genes of interest

and do the sequencing without destroying its

structure.”

The duo used a 3D printer to make custom

flow cells that would work with this hacked

sequencer and hopefully retain—and image—

the shape of the chromatin. Ideally, the hacked

sequencer would be able to look at a tumor

and record the individual transcription of

each cell, showing how the cancer develops

drug resistance.