Friday, July 9, 2010

Trio of GFP: Gem of Wisdom

Biology is not my cup of tea. For some unreasonable reason behind, I always feel such repulsion. Even, I took Environmental Science course instead of Biochemical Engineering course during my undergraduate study, only to avoid biology. So, the “synergistic effect” of at least three lectures made me “little bit understandable” of the term “GFP- Green Fluorescent Protein”, while those lessons were given by the three Spotters of this GFP!!!

Last year's chemistry Nobel Prize was one of the most softball predictions ever made for the Nobel Prize. GFP has become so widely used in chemistry, biology and medicine that it is easy to forget that someone had to discover it and develop the technology. Martin Chalfie, Osamu Shimomura and Roger Tsien, the trio was awarded Nobel Prize in 2008 for the discovery and development of green fluorescent protein (GFP), which is now an integral part of the life science.

Osamu Shimomura's talk is essentially historical. He starts by reviewing different types of fluorescent reactions in nature resulting in bioluminescence. A particularly striking example of bioluminescence concerns Aequorin, a small photoprotein in the jellyfish Aequoria victoria. In the presence of calcium ions another ring opening reaction takes place that produces blue fluorescence. Because of its dependence on calcium the reaction is a valuable one for measuring intracellular calcium levels.

Interestingly, Shimomura stated that most of the above findings were made before the 1980s. GFP and the revolution came later, but it would not have been possible if the foundation for understanding and studying bioluminescence had not been previous laid.

Later, Martin Chalfie starts by noting that the winning the Nobel Prize got him Andy Warhol's 15 minutes of fame. He showed us a Google news snapshot taken the day he won the prize which demonstrated that he had finally made it into the rarefied heights of the land of celebrities, very much in the same league as Britney Spears and Amy Winehouse!

Incidentally Chalfie used some unpublished results that his wife, who was also a biochemist, was working on. In return Chalfie had to promise his wife in writing that he would make coffee, cook her a French dinner and take out the garbage every night. This is one important take-home message for students and future scientists; science can involve some radical compromises with life.

Chalfie ended with a couple of important lessons about science:
1. Science is cumulative.
2. The students and postdocs are the real innovators in science. Many times it is easy to forget that they are the originator of some of the key details of Nobel Prize-winning ideas.
3. Basic research is essential and is the engine that drives innovation. Science cannot be done with too specific goals in mind.
4. All life should be studied, not just model organisms.

After the lecture, I took the chance to talk with this ever smiling down-to-earth personality, Chalfie. He seemed so happy to talk about his wife and most importantly her contribution to his research career as well as personal life.

Martin Chalfie with his big grin!

Roger Tsien talks a little about his own background. He is the youngest of 3 brothers and comes from a family of engineers and wanted to find a unique 'ecological' niche for himself. Charles Darwin was another youngest child, and he did manage to carve his own niche. Tsien was fascinated by colors from an early stage and became interested in biology and chemistry. One of the key points emphasized by Tsien was that young researchers should explore interdisciplinary areas where traditional barriers may prevent the transfer of knowledge.

Tsien, giving the lecture

Tsien then mentions some of the limitations of fluorescent proteins. They can be too big and their excitation wavelengths may not penetrate tissue. Plus the obvious scientific and moral problems associated with effecting gene transfer of GFP into humans are apparent.

Tsien concludes by talking a little about his current research which involves investigating metastasis. The work includes imaging tumors and nerves with GFP. Green tumors are easier to visualize and remove with surgery than non-fluorescent tumors. At the same time nerves should not be removed, and labeling them with a different color helps to avoid this. Imaging techniques provide a very sensitive technique for surgeons to distinguish unwanted tumors from necessary nerve growth. Tsien ended with a spectacular image of a plate displaying bacteria that have been colored by different fluorescent protein expression.

I can contemplate that Tsien, Chalfie's and Shimomura's talks held many notable lessons.

1. “You should take risks and work on big problems; even if you don't succeed at least you would have tried and learnt something.”
2. “Learn to make lemonade from lemon, sometimes persistence pay off” – Tsien.
3. “Accept that your best papers may be rejected from fashionable journals, or may be accepted for the wrong reasons.”
This was Tsien referring to the fact that his groundbreaking Science paper containing the crystal structure of GFP was initially going to be rejected after two bad referee reports, and was only accepted after the editors heard that a similar paper was to be published in another journal. Chalfie had similar problems when he wanted to have the word ‘new’ in his 1994 Science paper title, and then one of the editors thought the green-colored journal cover he had designed would look better in another color!
4. “Try to find important problems that put your neuroses to constructive work. Try to find projects that give you some sensual pleasure” – Tsien
5. ‘Prizes are ultimately matter of luck, so avoid being motivated or impressed by it’

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