Genome Center Sequencing Success: Mohan Narla Honored for Leadership

June 28, 1996

By Lynn Yarris, LCYarris@LBL.gov


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.

"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!"