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Feature

Inside Salk 12 | 15

www.salk.edu

DECODING THE BOOK OF LIFE

Manching Ku

holds out what looks like a glass

business card with four pencil-thin lines run-

ning across it. Each line is a channel that can

hold up to about 150 million fragments of DNA

from samples such as, for example, a diseased

brain and a healthy brain.

After one side of the double-stranded DNA is

stripped off, the sample-laden card—known as

a flow cell—is fed into a box-shaped machine

called a sequencer. The sequencer reloads

matching molecules, sequences of four nucleo-

tides (adenine, thymine, cytosine and guanine)

onto the DNA. But these replacement A, T, C

and G nucleotides are tagged with colors,

allowing a camera inside the machine to cap-

ture a snapshot of the newly colorized DNA and

decode what exactly those sequences are.

Despite only being made up of four letters, so

to speak, our DNA—and all the accompanying

bits that hang onto it—is still a puzzle to read.

It has been described as a book in which there

are no spaces or punctuation marks and with

letters thrown in at random. But decoding this

book is the key to understanding disease and

health, development and aging.

Manching Ku, director of Salk’s Next Generation Sequencing Core, holds a flow cell containing samples of DNA, which will be entered into a sequencer for decoding.

A flow cell can hold several million

fragments of DNA samples.

for integrating human stem cells into nonviable

mouse embryos in a dish. The work, published

in the journal

Nature

in May 2015, garnered

international attention for being a critical pre-

cursor to regenerative therapies.

“The core’s state-of-the-art technical support

for projects involved with the routine mainte-

nance, characterization and differentiation of

human pluripotent stem cells was critical to

this work,” says

Jun Wu

, first author of the

Nature

paper and postdoctoral researcher in

the Izpisua Belmonte lab. “The customized

basal media provided by the Stem Cell Core

was one of the key components for generating

these human region-selective pluripotent

stem cells.”

The discovery prompted much interest from

other labs at Salk, to the point where Boyer

acquired the chemicals and protocol for the

technique so that everyone could use it. She

is currently working with Wu to optimize and

outline an easy-to-use protocol.

“The cores are facilitators of research and

the hubs of collaboration—we make science

more cost-effective, time-efficient and robust,”

says Boyer.