From Genesis, Till Now
by Subhanan Banerjee, Team Leader, iGEM IISc-Bengaluru
It was by a mere coincidence that I came across a completely new thing in the field of biology, just by picking a random book from our Institute library: Electrochemical Biosensors by Sergei Cosnier. It was no sooner that the book opened the versatile interdisciplinarity of applied biology on my desk. I read the word ‘Aptamer’ for the first time in a chapter that showed how it has been used as a probe in electrochemical biosensors, how such molecules are synthesized and why they are strange in their ways. A thing that immediately caught my eyes was that Aptamers have the elevated property of structural selectivity, although they are less affine than antibodies. I was now in search of a field to apply the ‘exalted Aptamers’.
In the meantime, there was the buzz in the Institute of starting the ideation for the next iGEM cycle and so were the newcomers now being encouraged to take a step towards being Scientists. Everyone started making small groups of likely minds, proposing ideas, debating them, dreaming of them and so on. And so were we, a group of three: me, Suvam and Arjun. Long held talks across the classes and messes revealed our common interest in prion diseases. We certainly were more interested in the replication of Prions; How could that even happen sans a genome? We were spending lots of times in the library, across Nature and Springer or perhaps in search of a book that has all resolutions. It was the 1st of October, a bright day in Bangalore, we found a book that had a lot to offer… Prion Biology by Stanley B. Prusiner. It was a fallen wealth from Heaven! We learned a new thing, that some misfolded proteins can misfold their normal versions; mathematically, this is equivalent to regeneration. That’s beautiful! We got the key!
We had a clear version now, of how Aptamer can have a role in a field that we feared and loved too. ‘Aptamer Technology for Prion diseases’ – Doesn’t that sound revolutionary? We met Prof Varadarajan to tell our idea, he was highly welcome and just said, ‘You never know unless you try’ Truly speaking, iGEM was still an excuse for us, for brainstorming and intellectual discussions above academics. A. P. J. Abdul Kalam’s quote, ‘Dream with closed eyes and fulfil them when you wake’, so now was the second part. We must establish this now, this was not the part of science, something else, an exercise of our characters. So, our seniors started hearing us in presentations on Sunday nights. We also had a few other ideas like ‘Pathophysiology of auto-Erythrocytic sensitisation’ and ‘Increasing drug effectivity at Lower Concentration by localised adsorption’. Well, the latter also could involve Aptamers, but we loved the main idea. I remember disappointing my roommate once due to meeting in my room, that was funny, now but a good memory. It was that Autumn evening that Suvam proposed that why not we span it across other such conditions arising from misfolding of a protein? Now, a new challenge, what are such conditions?
In gradual pace, we found that Alzheimer’s, Parkinson’s, Huntington etc are all real-world examples. In fact, most neurodegenerative diseases are because of protein misfolding oriented cascades! We wanted to believe that Aptamers can be solution to all of them but were sceptical enough, we understand now that’s how science works. We realised that doing experiments with Prions is a bit impractical for us, so we kept it for another day.
Then came the winter, homecoming season for most of us. Suvam made an WhatsApp group and christened it ‘Misfolded Folks’!
The second semester was perhaps a bit filled one, due to optional subjects, assignments, quizzes and exams. So, our frequency of meeting was a bit less now. It was on a Sunday night after meeting the seniors I remember that I spoke to Anurag, who was by then in another team with Avani and just preceded the moment speaking about Alzheimer’s theranostics. I said like a salesperson ‘You may like to use Aptamers’. That was the birth of a new collaboration and slowly the two teams became one (Unification of Germany!). We now wanted to select any one disease as a model… So, we distributed the diseases among us! Suvam was on Parkinson’s, Manya who had recently joined our team was on Huntington’s, Anurag and Avani were on Amyotrophic Lateral Sclerosis (ALS), Arjun on Alzheimer’s and I was on Tauopathies in general. We figured out! Tau phosphorylation had something to do with the misfolding and we were clear we wanted to use it as a Biomarker. We met Prof Muddashetty from the Centre of Brain Research and realised that we may have a solution but with yet got posed with another challenge: Tau phosphorylations leads to misfolding and the cascade of neurodegeneration but are highly variable. He said that it is only the average phosphorylation that increases up to 8 and is still not well established. Statistics! Now we understand why statistical physics was developed, macroscopic properties are oftentimes more reliable than individualised properties.
This was February, and we were heading to decide a team representing the Institute. But how could it be done unbiased and well-spirited? There were two major groups now, us and Parth’s. Parth, Anushka and Geeth had been working on strategies to cure Type 1 Diabetes, an autoimmune disorder, using Foxp3 transcription factor to create bihormonal cells and facilitate an alternative mechanism of insulin exocytosis. Suvam proposed a panel consisting of our iGEM experienced seniors and an anonymous voting after successive presentation. I heard Parth’s idea that day, properly and completely and realised it was as good if not better. It was completely something else than expected. The seniors stepped back from choosing! I personally, who was thinking Parth as a competitor, was stunned when he joined hands with us happily on his own. Now, there was one single team, unified with science, bonded with dreams.
The team had to get the coordinators and leader and that’s why the experience in the cycle wasn’t only
of a scientific rollercoaster. The team voted me as the Team Leader and Suvam as the co-Team Leader.
From administering a team to facing the issues with the administration, it was all like the lines of a
bildungsroman novel.
The intermittently worked day and night to resolve the flaws in the idea, checked with Professor Varadarajan and Muddashetty frequently. Our PI, Prof Deepak gave us the contact of a few experienced researchers on the relevant field at the Brigham and Women’s Hospital; Dr Nagendran, Dr Lei Liu and Dr Jean-Pierre Bellier. We obtained lots of prospects from them.
During the summer, everyone went to some lab or the other for training and internship. It was too, an exercise of balancing all your interests after all… We met every week during this time, planned the experiments and ordered the materials. Well, after all when the wet lab started, we faced several issues and failures. But that’s a part of life, right? Trying our best is the only thing we have in our hands. The semester also started by then. I remember how hard Suvam used to work in the labs, he really sacrificed a bounty of sleep. Nevertheless, we still had a lot of fun… We oftentimes met in front of the main building of IISc, which is itself an inspiration that helped us keep going. And I remember, on one such meeting Avani ordered a huge pack of ice cream and we all shared from the same. We never realised when a team crafted for a motive, slowly transformed into a group of friends, where each one was a peculiar character: Parth the teacher, Suvam the happy-go-lucky guy, Anurag the chemi-passionate, Manya the reserved lady, Avani the bold girl, Arjun the innocent, Anushka the illustrator, Geeth with the distinctive accent, Harish who laughs more than he speaks, Shouvik the Neuroscientist and many more…
