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Stemming Sickle Cell (con't)Chris Hartlove

Stemming Sickle Cell (continued)

The Mentor Chain

When he was still in India, Ramalingam, who earned his doctorate in molecular biology from the University of Madras, studied strategies for boosting the iron content of rice through manipulating the crop’s genes.

That’s how he heard about Chandrasegaran’s groundbreaking work on zinc finger nucleases, called ZFNs, as a tool for tweaking DNA. “Chandra was the expert,” the younger scientist says. “I sent him my CV and wrote that I was interested. I was very fortunate to work with him.” He came to Hopkins in 2008 as a postdoc to work with Chandrasegaran in EHS.

One advantage of ZFNs and similar gene-editing technologies, Chandrasegaran says, is that, made carefully, they can be targeted at one and only one point in the genome, avoiding the damage that can be caused by random insertion. (Sickle cell disease is caused by an error in a single chemical “letter” in the 3.2-billion-letter-long library of human DNA.)

But making these precise tools for cutting and editing DNA isn’t always simple. Ramalingam says he probably faces another two or three years of working on this crucial phase of the effort. “The success rate is very, very low here,” he says. “So you need a lot of patience doing this research.”

The postdoc, who is married with a 10-month-old son, says he was very proud when his parents traveled the 7,000 miles from his tiny home village of Kullampalayam to visit the Baltimore lab. “They were very excited, they were very happy,” he says. “I tried to explain it to them and the basics, they understand. But the technology, they may not yet.”

While the sickle cell project could accelerate Ramalingam’s career, his senior partner in the lab is considering retiring after three decades at the School.

“Whenever I end up with problems, I discuss them with [Chandra]. He’s a great advisor.”
—Sivaprakash Ramalingam

Chandrasegaran, who grew up as one of 10 children, is the son of a customs official working in what was then the French colonial city of Pondicherry on the Bay of Bengal. Accepted to an elite state-run military secondary school, Chandrasegaran rose to the rank of house captain, excelled at physics and graduated with honors. “All my friends who right now are in India? They’re generals and air marshals,” he says.

But he decided to become a scientist rather than an officer, earning a degree in chemistry from the University of Madras in India and his doctorate from Georgetown. He came to the School as a postdoc in late 1981 and joined the faculty in 1986.

At Johns Hopkins, Chandrasegaran learned molecular biology at the bench of Hamilton Smith, professor emeritus at the School of Medicine and a key scientific strategist for a private company that published a working draft of the human genome in 2001. Smith shared the 1978 Nobel in physiology or medicine with Hopkins’ Dan Nathans and a Swiss scientist, Werner Arber, for the discovery of restriction enzymes, the first chemical tools for editing DNA.

It was Smith, in fact, who suggested that Chandrasegaran pursue the synthesis for new gene-editing tools. That suggestion eventually led to Chandrasegaran’s groundbreaking work on ZFNs—technology that, Smith notes, “is now leading to discoveries of several new ways to cleave DNA in site-specific fashion without using restriction enzymes. It’s a hot new field with implications for gene therapy and genome engineering.”

“I had a great teacher,” Chandrasegaran says. “I followed him. He got me interested in molecular biology, in restriction enzymes.”

Ramalingam, in turn, says Chandrasegaran has inspired him by spending long hours in the lab and generously sharing his skills. “Whenever I end up with some problems, I discuss them with him,” he says. “He’s a great advisor to me.”

Comments

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  • AFOLABI WASIU

    NIGERIA 10/14/2012 07:31:10 AM

    Congratulations to these scientists for daring to take up this challenge. I can only wish them success as humanity will never forget anyone that will rid the world of these deadly scourges. There will be light at the end of the tunnel

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