How the young brigade mapped the TB genome

April 15, 2010 02:50 am | Updated April 16, 2010 06:24 pm IST

NEW IMPETUS: Mapping of the TB gene may expedite the discovery of a new drub for the disease. Photo: AP

NEW IMPETUS: Mapping of the TB gene may expedite the discovery of a new drub for the disease. Photo: AP

When nearly 400 motivated students, with the help of a few faculty and scientists, get together voluntarily and work single-mindedly, solving any complex problem can turn out to be child's play.

These students, with a few exceptions, were trying to solve a complex problem during their free time after attending classes or studying for an exam. They spent more than six hours every day for four months to achieve their goal.

That the entire exercise was done through online interaction did not in any way cause any problems. They succeeded though some of them had never studied bioinformatics, so essential for such work. What is significant is that some were only doing their under-graduation.

The fact that there would be no monetary gain from solving the mega scientific puzzle had little bearing. Many of the students had never read a peer-reviewed paper published in journals like Science and Nature .

That, in a nutshell, is the story of how the young brigade went about mapping the TB genome in just four months despite many limitations.

The TB genome contains nearly 4,000 genes. The functions of nearly 1,500 genes were not known. And a flood of information contained in hundreds of published peer-reviewed papers was to be culled out. And for those genes that were not annotated (functions not known), the predicted functions were computationally extrapolated by them.

Quality checks were done onsite by students and their Principal Investigators (PI). The TB gene map was finally produced by combining the already annotated genes and those that were computationally extrapolated.

“Within two days of giving an open call to students to join the Connect 2 Decode (C2D) project, we got about 850 applications. Most of them were from students,” said Mr. Zakir Thomas, Project Co-ordinator. C2D is a part of a large Open Source Drug Discovery (OSDD) project, and Mr. Thomas is the Project Director of OSDD.

“The students were given a small exercise to solve. It was a kind of screening,” said Dr. Anshu Bhardwaj, one of the Principal Investigators of the project. She is a scientist at the Delhi-based Institute of Genomics and Integrative Biology (IGIB). About 400 students were selected.

Mapping the TB genome was done by splitting it into five themes, and students were free to choose any of them. Each theme had one Principal Investigator. “All the 400 students made some contribution, but significant contributions came from about 250 students,” said Dr. Bhardwaj.

The students were first trained for a month. And the project began in full earnest in January this year.

The road block

But two weeks into the project, the PIs had to make a midcourse correction. The initial structure was to have for each theme a Principal Investigator and a faculty co-ordinator who would work closely with the students. But no inputs were coming in for a few days, and the reason soon became apparent. The faculty co-ordinators were choking the system!

“So we asked the students to get in touch with the PIs directly,” said Mr. Thomas. And there was no stopping since then.

Trepidation

“I am an experimental scientist, and it is easier for me to have students before me and monitor them. But in this case they were spread out and everything was to be done online. I was nervous in the beginning,” said Dr. Sulagna Banerjee, PI for one of the five themes. She is a Scientist at AU-KBC Research Centre, Anna University, Chennai.

“Initially, I was not sure if it would work as I had not met them. I was sceptical. Initially, there was a big learning curve as the students were not used to reading [journal] papers.

“But they soon learnt after going through a few papers,” said Dr. Samik Ghosh, PI of one of the five themes. Dr. Ghosh is a scientist at The Systems Biology Institute, Tokyo.

The initial reaction was no different with Dr. Bhardwaj either, who was a PI of another theme of the genome mapping project.

Gained confidence

But the scepticism soon gave way to confidence. “Happy to tell, I got a feeling that I was wrong. I was gaining more confidence. Students could quickly get the essence of building the network,” Dr. Ghosh said. “I was really swept off my feet when I met them. [I was] completely surprised at a girl's confidence to learn.”

Dr. Banerjee said: “I really did not realise students' potential would be like that. It was really amazing.” The proof of the pudding came at the end. One part of the project was considered very difficult and was kept aside to be taken during onsite (where it was a face to face interaction). “20 students completed it in seven hours straight,” she added.

What surprised many PIs was that students managed to work during their free time. “That surprised me a lot. I was amazed as they had classes and exams when they were doing this work. They were working on this even during their holidays,” Dr. Banerjee said.

The volunteers

Harsha Rohira of Acharya Narendra Dev College, Delhi University, though the youngest member in her group, was a mentor for others in her group. This, despite having no background in bioinformatics, which is so essential for this kind of work. She is doing her second year under-graduation in Biomedical Sciences.

For Harsha, after college hours meant working on the TB project. “I was doing the entire work from 7.30 pm till 4 am, every day,” she said. It only got more gruelling during the onsite work at Ghaziabad. “We used to work from 9 in the morning to 3 am [the next day]. I would then study for my exams for 2 hours,” Harsha said.

“I got exposed to bioinformatics and learnt how to use very large databases,” she added.

For Prabhakar Munusamy, a final year year B.Tech student of PSG College of Technology, Coimbatore, Tamil Nadu, the diffidence gave way to confidence very soon. “I was not very confident that I could do it. I did not know what it was all about but I soon got interested.” he said. “But now I can do annotation for other organisms. I am happy now. At last, I am part of a big work.”

Working in an office did not stop Rajdeep Poddar based in Pune from working on this project. “I used to work three hours every day. Missed a few days, but made it up during weekends,” he said. “The project gave me a big exposure. Working on a large project and doing it online was interesting.”

Though Poddar has learnt the various bioinformatics tools during his post graduation, this was the first time he used them. “It gave me hands- on experience working on real data that would be used for drug discovery,” he said.

For J. Laxmanan who is doing his Ph.D under the guidance of Dr. Banerjee, at Anna University, Chennai, working on this project was a wonderful experience. He had worked for three years after his post-graduation. “Whatever I learnt while working helped me; it was a wonderful experience,” he said. He has gone one step ahead. “Have identified some very good drug targets,” he noted. He would be doubly benefited by this project. His Ph.D work is about validating the predicted functions of the genome.

Dr. Ghosh has the last word. With an international exposure in the U.S. and now in Japan, his impressions about Indian students have changed drastically. “From my experience, if these students are given the same encouragement, they can perform like any other student from any developed country,” he said. “It is essential for India to provide the environment and motivation for students to excel.”

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