Lab 108: Big Ideas, Bare Basics.

 

I have often wondered whether one really needs a well-heeled laboratory to do innovative work. Having seen labs at both ends of the spectrum, I am still not quite sure. But my two-and-a-half years at the Indian Institute of Science, gave me plenty to think about.

I had moved from Banaras Hindu University (BHU) to the Molecular Biophysics Unit (MBU) at IISc - colloquially called the Tata Institute - and joined the laboratory of  Dr. Samir Brahmachari. He was Samir or SKB to many, but simply “BOSS” to us.

During my PhD, I had visited CCMB, perhaps the only “five-star” research institute of those times. That visit had helped me build a rather dazzling picture of what IISc would look like. 

Then I walked into Lab 108.

It was quite basic.

There was one large laboratory with workbenches, no air-conditioning and large windows that usually remained open. In one corner, BOSS held court, gently swinging on a Godrej chair sometimes puffing away at his cigarette. A small air-conditioned room was mainly used for running gels, the most prized machine there being the pulsed-field gel electrophoresis system.

The passage outside served as both a seating area and a place for bacterial work. Seating followed the musical-chair principle.

Bacterial inoculations were done on an open bench between two powerful gas burners. During this delicate operation, the main laboratory door was locked to prevent “contamination.” Interestingly we rarely had contaminations in this open contraption. But when BOSS got money and bought us a culture hood we ran into trouble!!

Pungent chemistry was pushed into a small room with a fume hood. The laboratory’s most protected possession was a water bath permanently set at 37°C. Nobody dared touch its knob because there was no guarantee that we would ever find 37°C again.

The same water bath was used for restriction digestions and bacterial transformations. To hell with Maniatis’ prescribed  42°C heat shock. 

There were, of course, other common facilities scattered across MBU and neighbouring departments. But within Lab 108 itself, what we would today grandly call “infrastructure” consisted largely of this - and probably a minus 20 freezer and a glass distillation unit tucked in a corner.

What the lab lacked in equipment, however, it made up for in ideas.

It brought together biologists and chemists under a BOSS who could become wildly excited with  questions and new technological ideas. While I was still finishing my PhD, I had heard SKB speak about how unusual structures in DNA could affect gene expression. I think the structure was then called Form V DNA - essentially a cruciform structure.

I understood only parts of the lecture, but his enthusiasm was hard to miss. When I spoke to him afterwards, he simply said, “Come and join me after your PhD.”

I took him seriously. After pursuing him through a series of inland letters - there were no emails to chase people with - I finally landed in Lab 108, without fully understanding what I was getting into. But then, this was IISc, the Mecca of Science, as some liked to call it. Surely the rest would sort itself out.

Around 1990, we were quite a bunch.

There were PhD students and postdocs: Bagga, Meera, Balagurumoorthy and Partho, who had entered through the grill of written tests and interviews. Eugenia was an external PhD student. Then us the postdocs selected, I suspect by BOSS’s eyes and heart: Jalaj, Akhilesh and Ranjana, all three from what was then Allahabad (sorry can’t keep track of the changed names) and me, the slightly lost one from Varanasi.

And Oh! how can I forget Usha, who seemed to take care of everything? 

The young boy (sorry can’t remember his name) who came in once in a while to wash the glass wares.

Sowmya joined soon afterwards. 

We were a lively mixture of chemists and biologists, held together by curiosity, confusion and our effervescent BOSS. The science was as varied as the people.

Bala, Akhilesh and perhaps Ranjana synthesised oligonucleotides and studied their structures, with a common circular dichroism machine in MBU as their mainstay. Lab 108 was probably among the first semi-commercial ventures in India to synthesise and supply oligos across the country.

Bagga followed the work on cruciform DNA and how it could block transcription. Partho explored another unusual DNA structure - the triple helix. 

Eugenia worked with a protein purified from wheat germ that could bind left-handed DNA, or Z-DNA.

Jalaj’s prized possession was the pulsed-field gel electrophoresis system, on which we separated yeast chromosomes. We also made yeast plugs that were sold as size markers for PFGE through Bangalore Genie. Lab 108 had quietly entered business (no need for current day BIRAC and BioNests). 

Meera worked on nucleosome mapping  using a complicated two-dimensional electrophoresis method and borrowed radioactivity. The developed autorad decided whether she smiled or announced that it was time for coffee. Sorry, Meera, I no longer remember the exact details, but I do remember that the work looked frighteningly difficult.

When Sowmya began, she set about establishing a new sequencing technology. 

Each project involved a technique that was difficult, uncertain and, in several cases, not being attempted elsewhere in the country. Perhaps the absence of impact factors, citation scores and API calculations helped. We thus took on problems without first asking how many points they might earn. Of course, all of us had our ups and downs - but the questions were never small.

As for me, I was dazed and dazzled in roughly equal measure.

I tried my hand at protein purification, gel retardation, gene expression, yeast chromosome separation and some of the mysteries of oligo synthesis. CD remained beyond me, though I picked up enough jargon during smoking breaks with Bala to later exaggerate my knowledge quite convincingly. I occasionally peeped into Meera’s work but wisely kept a safe distance.

Eventually, I became part of a project that asked how the long trails of A, T, G and C expected from the Human Genome Project could be represented, viewed, analysed and stored. At the time, this was a challenge very few people in India were even thinking about.

We developed a program that we lovingly called GENOME MAPPING.

Today, when an entire genome can travel in your pocket, it is difficult to explain how strange and ambitious that question seemed more than three decades ago. For me, it became a steep learning curve and changed the way I thought about science.

That story deserves a blog of its own.

Lab 108 did not have dazzling infrastructure. What it had were ideas floating freely, people willing to attempt the difficult and a BOSS whose excitement was wonderfully infectious though sometimes……!!

I spent only two and a half years there. But what I picked up in that modest, open-windowed laboratory, with its musical chairs, smoking breaks and untouchable water bath carried me through the next three decades.

Perhaps Lab 108 did have five-star facilities after all. They were simply housed in the people 😀, not the building.

Disclaimer: This is Lab 108 as I remember it after more than three decades. Pardon me for any omissions, mix-ups or scientific liberties.

The lab had little polish, no grandeur in sight,

But ideas burned there, fierce and bright.

Sowmya giving SDS, Meera and Usha listening intently and me the only one working sincerely. 1992.. at a International Conference hosted at Tata Institute.

BOSS (far left)  his usual self with other DNA structure stalwarts.. year 1992