Genome Center Sequencing Success: Mohan Narla Honored for Leadership
June 28, 1996
By Lynn Yarris, LCYarris@LBL.gov
"I want to call your attention to the pivotal role played by Mohan
Narla in the success of our Human Genome Center," said Berkeley Lab
director Charles Shank in a message read to attendees of the
celebration by Deputy Director Pier Oddone. Indeed, all of the speakers
at the morning-long event, which included LSD Director Mina Bissell,
new HGC Director Mike Palazzolo (see June
7 Currents), and HGC leaders, began their remarks with
acknowledgment of Narla's contributions. All were especially mindful of
the stability he brought to the program.
"All of our success has been achieved from within," Bissell said. "With
little help from the outside, Mohan worked with our own people to put
our Human Genome Center on a tract that has made it one of the top
genome programs in the country."
Palazzolo also praised Narla's stewardship. "Mohan did a selfless thing
at the prime of his scientific career. He took the time to marshal the
resources here at the Human Genome Center, said the future is in
sequencing, and pointed us in that direction. We are healthy today
because of it."
He noted that HGC researchers are now sequencing at the rate of 500,000
base pairs a month, which is more than what they could do in an entire
year prior to Narla's acting directorship. To date, the HGC has
sequenced nearly 5.5 million base pairs of DNA (human and drosophila),
a total that is second in the world only to the base pairs sequenced
for the nematode genome by the collaboration between Washington
University in St. Louis and the United Kingdom's Sanger Centre.
It is in the sequences of the base pairs of nucleotides that make up
DNA that the genetic code of life is written. The full complement of
DNA needed to create any individual organism is called a genome. The
human genome is one of the most complex (though not the largest), made
up of three billion base pairs which are organized into 23 chromosome
pairs. It is the goal of the Human Genome Project to sequence all three
billion base pairs, determine which are used in genes, and map their
location along the chromosomes. The project, which is jointly sponsored
by the U.S. Department of Energy and the National Institutes of Health,
has been called "biology's flight to the moon."
With guidance from Narla, Berkeley Lab's HGC shifted from its original
focus on mapping chromosome 21 to developing and implementing a
cost-effective and accurate "high throughput DNA sequencing"
capability. Though Narla's vision got the ball rolling, credit for the
Center's subsequent success is shared by all of its component
programs.
Chris Martin, who now leads the HGC's sequencing group, discussed the
role played by the "directed approach" to sequencing which he and
Palazzolo developed with other members of the group. Unlike the
strategy followed by most genome groups, in which random coverage is
expected to yield a complete sequence, the directed approach employs
"sequencing templates" that have been mapped to a resolution of 30 base
pairs. This greatly reduces the labor and difficulty for genome
sequencing.
"In a single year, we have tripled our productivity per staff member,"
Martin said. The goal of the Human Genome Project is to complete the
sequencing task by the year 2005.
Everyone associated with the genome project acknowledges the critical
importance of automation. In her introduction of Joe Jaklevic, leader
of the HGC's automation group, Bissell expressed admiration for what he
and his group have accomplished.
"Joe has been the embodiment of the effort to bring high-technology
into the life sciences," she said. "One of the major reasons that our
Human Genome Center has been so successful is the incredible work of
the automation group."
In his presentation, Jaklevic used a chart to graphically illustrate
that more than 80 percent of the base-pairs sequenced at the HGC have
been achieved in the past couple of years. Berkeley Lab's HGC was
established in 1987.
Among the innovative technologies introduced to the Center by the
automation group, Jaklevic cited such examples as the high-speed
automated colony picker and arrayer, the CCD system for digital image
processing, the high-speed thermocycler for PCR assays, and the DNA
preparation robot.
"Most of our increased production rate has come from eliminating
bottlenecks in the (sequencing) process," Jaklevic said. "DNA
preparation has been a huge bottleneck." He noted that a sequencing
rate of 20 million base pairs a year, a goal envisioned by our HGC,
requires a lab to be able to prepare five microtiter plates of DNA
material a day.
"Our DNA prep robot can do five plates in a couple of hours," he
said.
The other speakers that morning were Bruce Kimmel, who spoke on the
future of genome research, Edward Rubin, who heads the HGC's biology
group, Frank Eeckman, who heads the informatics group, and Gerald
Rubin, who heads the drosophila sequencing center. The message was that
substantial progress has been made and the pace is rapidly picking
up.
"We (at Berkeley Lab) have become the lead sequencing center for DOE,
and we are really going to build an automated sequencing center--which
is what DOE was charged to do," Palazzolo told the audience. "Today is
a celebration!"
Mohan Narla of the Life Sciences Division was
the toast of the crowd gathered at the Bldg. 66 Auditorium last Friday
to celebrate the achievements of the Lab's Human Genome Center under
his stewardship. Narla, who served as the Center's acting director from
1994 until this month, is credited with providing the leadership that
helped transform what had been a struggling program into one of the
nation's most successful.