Many articles have already been written about research and the intricacies of a life in it. Most of them, though, are from the perspective of graduate students; written by graduate students themselves, or people reminiscent of their time in graduate school. This is probably because that is when a person generally evolves from a student into a researcher, and it is during this transition that the properties of life in research become more stark. The entire point of the IISc undergraduates participating in the iGEM competition was to shift this frame slightly to the left in the timeline. All of us were under the impression that the researcher in us, though far from being developed, has already started developing. iGEM, to us, was a path to verify this rather ambitious speculation of ours.
iGEM stands for International Genetically Engineered Machines (I never really understood why the ‘i’ is in lowercase, but in defense of the ‘i’, ‘I’ never really ventured to determine the reason). As the name suggests, it is an international synthetic biology competition, mostly for undergraduates, though some high-school and over-graduate teams also participate in their respective categories. It started out as an effort from MIT to standardize plasmid backbones. Most people who do wet-lab work regularly in biology, would have faced this problem — “I have my gene of interest in plasmid A, and I want to put it downstream of some other gene in plasmid B. I need restriction enzymes m, n, o, and p for this relatively simple exercise, but there is no enzyme ‘q’ in the lab! Now all I have to do is get a quotation for it from the vendors, wait for about 6729 years for it to arrive while I finish a few more seasons of my favorite TV series, and lament after 20867 years how excruciatingly long a PhD in Experimental Biology takes to complete.” The next time a similar experiment needs to be performed, suddenly enzyme z is out of stock and the same sequence of events repeats. Instead, if most plasmids come with cut sites of a specified (and very small) set of restriction enzymes, having those in stock will be sufficient to do most research work. iGEM started an attempt to make a library of plasmids with specific cut sites (which, certainly, should not be present in your gene insert), and develop/validate this library either by using or improving the pre-existing plasmids (known as BioBricks), or making a new plasmid that fits the library criteria. Possibly the reason for the target participants being undergraduates, was because a failure for them is much less costly (with no PhD thesis at stake!), and because of this, they often tend to explore improbable regions, with hidden answers.
Like most student initiatives, the idea of forming an iGEM team came to us one day, over junk food, late at night, in our first semester at IISc. Arunavo, being a YouTube-phile, had come across a video of the formation of the iGEM team of King’s College, London, and suddenly, we thought, “Why can’t we have an iGEM Team?”. The next day, we went and talked to our instructors, who were pretty interested at the prospect, and took an active interest in discovering what the competition was and why it is worth participating in. But, like most sudden peaks of academic excitement and interest that originate in one’s hostel room, it died away soon. Thankfully, our instructor (Dr. Narmada Khare) had not forgotten about the conversation we had, and one day, while conversing with a PhD student at NCBS (National Centre for Biological Sciences, Bangalore), she came to know that this PhD student, known to her colleagues as Chaitra Prabhakara, was a member of the IIT-Madras iGEM team in her undergraduate days. Both Narmada and Chaitra considered the formation of an IISc iGEM Team a possibility, and Chaitra came and gave us a talk about her experience with the competition. That was the activation energy we needed, and a team suddenly formed out of thin air, comprising of 21 students (of course the number is not exact; all I can say is that it is of the same order of magnitude as the original number!). Anyone with any interest in biology was willing to help.
As many would have noticed in their personal life, or in the dynamics of academia around them, in the initial days after formation, the number of members in an undergraduate team follows a roughly exponential decay, until it hits a threshold number. Interestingly this threshold is often a number which is practically the minimum requirement of calling a collective a team. It finally settled down to the four of us — Abhijeet, Arunavo, Shreyas and I (Prabaha). Actually, at a point of time, the team was practically two people — Arunavo and Abhijeet, because Shreyas and I were busy discovering our startling incompetence at even starting to solve an assignment anytime before ‘the-night-before-the-deadline’. Now, since both of us were taking a lot of courses, once we solved an assignment at the last minute, the next day was always the last minute for some other assignment/test. Eventually, this oscillation in the number of members settled down, and the four of us consented in each other’s calling ourselves part of the IISc iGEM Team, which was still to be recognized by the authority – the Undergraduate Department.
The next step was the rate determining step — convincing the authority of the existence and legitimacy of the first team from our college. No one had any problem with undergraduates trying out original research; after all, the entire objective of the UG program was to promote exactly this! But, the problem is, there exist factors like intellectual property rights, and many more words, whose exact definitions still elude me, which noobs like us had not exactly accounted for (to be truthful, we had, but iGEM was open source — a philosophy we wanted to be a part of, but the authority was still getting used to). Also, $!
After multiple discussions, Prof. Umesh Varshney, the UG Dean at that time told us one of the most encouraging things we had heard, “You people take care of the science, and we adults will handle the bureaucracy”. What more does an undergraduate need? We had spent almost one and a half years, discussing among ourselves, and getting our ideas validated (generally rejected) by Chaitra, Sachit (another PhD student from NCBS) and our biology instructors in finally coming up with an original idea that was interesting, and could be verified in the time window (roughly the summer time). But research needs funds, and though the UG department had funds, it was allocated for specific purposes. We discovered a competition called iBEC that was being organized by DBT (Department of Biotechnology) for the very first time that year, for Indian iGEM teams. The teams had to submit a grant proposal, and a select few teams would receive financial aid up to an amount of Rs. 10,00,000. We got the complete Rs. 10,00,000 that we had asked for. The UG department loaned us the registration fee (~Rs. 4,00,000), because the iBEC results were to be announced after the deadline to register for iGEM, and thus the IISc iGEM Team was officially established, lead by Prof. Deepak Saini from the MRDG department (Molecular Reproduction, Development, and Genetics) and Prof. Umesh Varshney, the contemporary UG Dean. We even took in 3 of our juniors — Aiswarya, Aneesh, and Ayan, so that next year’s team got a head start.
Then began a stream of failed experiments, with one or two successful ones in between, and the not-very-uncommon waiting periods for enzymes to get delivered (I know that the entire point of iGEM was to avoid this very thing, but one or two of the iGEM prescribed restriction enzymes were not the most commonly used ones in our labs). But that is all known to anyone who has done science; most people reading this article can teach advanced courses on failed experiments, and I am just a beginner. The challenging hurdles we faced, other than the scientific ones, were the non-scientific ones. I won’t be surprised if someone now shouts, “10 points from Ravenclaw for stating the obvious”, but what one needs to understand is that we had no idea about how to solve the non-scientific ones. The registration fee ensures the recognition of the existence of the team, and the shipment of a collection of pre-existing BioBricks; it does not cover for anything else! When the team goes to present at the Giant Jamboree (the event at which the teams present their work) another registration fee for each team member had to be paid, and that, again, covered nothing else. We had to arrange for our own lodging, food, and travel. We needed to raise more money for that, the amount promised by DBT was not even close to sufficient!
Thus, in addition to spending sleepless nights in the UG bio labs doing experiments, we started thinking about how to get more money. Our professors promised to manage the money, and even help us get it, but we had to come up with the sources. We jotted down the list of funding agencies that help startups, successful startups that might be interested in our work, people who might help us point towards a source of money, and started emailing any and everyone. One day I was talking to Kuldeep from MBU (Molecular Biophysics Unit), a PhD student I worked with in my first summer, lamenting about the soup we were in, and he told me about the existence of a Facebook group called Career Support Group (CSG), comprising largely of IISc students and alumni. I thought that this group might help stranded IISc students going abroad get a place to stay. It took me some time to discover that the pre-stated description of CSG was as complete as calling a university a place with classrooms.
The first post I made on the Facebook page was requesting the members to allow the team members to stay at their apartment(s) for the duration of their stay. The response was overwhelming! Many people offered us a place at their apartment, but it was not limited to that. Dr. Selvaraj Nataraja from the group proposed that we try crowd funding, so that we could book an apartment for the entire team, and gave us a seeding amount of $300. Dr. Ananda Ghosh, the founder of the group contacted us and advised us to campaign in the group — regularly post about who we are, what we are trying to do, about the program we are a part of, about the Jamboree and the associated opportunities and exposure, etc. In addition to learning to do science, we started learning people skills, and the methods of pitching and funding one’s research endeavors. Finally, after campaigning, we asked the CSG members to help us in organizing the fundraising, and Dr. Kushagra Bansal (an IISc alumnus, and currently a Postdoc at Harvard) took up the responsibility of collecting the money for us. Once again CSG surprised us with its response and within a week, we had raised enough money to book an apartment for the duration of our stay.
In the meantime, we were trying other avenues to get funding for our travel and sustenance, and we managed to convince the IT, BT and S & T department of the Karnataka Government that our project was worth funding and got a grant worth Rs. 6,00,000 (toward consumables) from them. Also, we had applied for the Indian Alliance (Wellcome-DBT) travel grant, which is generally meant for PhD students, but surprisingly, we got that grant too! IISc-AANA (Alumni Association of North America) also agreed to make payments for the rest of the predicted amount of money required. Finally, we had all the money we needed. All that was left was the science.
If one tries to track the evolution of the answer to the question “What exactly are we trying to show?” in a project, often, the trajectory takes massive downward leaps along the axis of ambition. Our case was not much different. Our idea made sense, the genetic circuits made sense, the two modules we made also made sense, and so did the expected crosstalk between them. The only thing that did not make sense was the amount of time all the experiments we designed were taking to perform, and the astounding number of parameters that cause failures and delay work by days — reasons like “The liquid nitrogen we brought this morning has evaporated” or “The glycerol in the polymerase caused the entire PCR mix to precipitate (it took us a good part of a month to discover that that was what was going wrong with our PCRs; also, some wells in the PCR machine were not working!)”. Finally, when the week before our date of travel arrived, we had got both the modules to work independently, but did not have time to show the effects of combining both of them in a cell. We decided to present what we had done, and that in itself involved new scientific work, but were dissatisfied at the fact that we did not quite live up to our soaring ambition.
Finally, Abhijeet, Arunavo, Aiswarya, Srinath (instructor), Shreyas and I headed towards USA to present the work of IISc-UGs to the world. All of us were so relieved at the last minute completion of experimental work and documentation, it did not occur to us that we should be feeling excited about where we were going and what we represented.
None of us had ever visited Boston, but we did not feel any degree of alienation when we reached, on account of Dr. Kushagra Bansal and Dr. Gajendra Dwivedi (another CSG member in Boston) picking us up from the airport. That night, all of us enjoyed the placid, dreamless sleep brought on by exhaustion from the journey. The next day, all of team but I explored Jamaica Plain while I went to meet a professor I had mailed about the coming summer. The meeting was fruitful, the trip not only enabled us to present our work but also got me a funded project for the next summer at Harvard. On that same day, Dr. Selvaraja took us all to dinner; at this point, Boston was almost a home away from home. It was after the dinner that we realized that we had a significant portion of our presentation to complete, thanks to some experimental success right before our departure. In addition to the content, the design of the presentation was crucial; a brief look up of past years’ winning presentation revealed style was almost as important as content and delivery. And thus began a highly awkward yet effective process of outsourcing the design to India; a couple of our peers — Prokash and Sai had volunteered to draw the figures and design the layout of the presentation respectively. Another realization struck us on the night of the dinner – the poster needed significant revision; it has too much text and too few illustrations. We sat through most of that night annotating the pdf version of the poster with the changes and mailed it to Sai to implement. We needed the poster on the very next day!
We made the poster deadline (thanks to a nearby Kinko’s and the design team’s efficiency) and rehearsed the presentation in a room set up very similar to the way the presentation hall would be. We realized some visibility problems (some of the text was too small) and headed back home. Further changes were mailed to the exhausted design duo and we continued with a flurry of rehearsals during the next day and a half that finally culminated in our actual presentation. It went well, except for some unrehearsed time allotments to the different presenters. A wave of relief washed over all of us. Only 2 more days of poster presentations and we would know the result of our year and a half of blood, sweat and tears. We ended up winning a Bronze medal in the competition (not to be mistaken as the third prize; many gold, silver and bronze medals are given out, somewhat like the Olympiads). We had also contributed to something called the ‘InterLab Studies’ where volunteering iGEM teams across the world perform a particular prescribed experimental protocol, and produce robust statistically significant data. The theme for 2016 was standardizing fluorescence quantification. When we attended the InterLab committee’s presentation, we heard some ‘IISc iGEM Team’ had suggested a correction to the experimental protocol, that had reduced the error margins by 100x. “Must be a team of astoundingly brilliant students”, we thought.
We also spent a significant amount of our time watching other teams present. A trend we observed about the teams whose work was extremely elaborate (a large fraction of these teams eventually went on to win lots of awards) was the significant role of graduate students and Postdocs – some of these teams had up to 20 such researchers acting as mentors in addition to the PIs. And suddenly it hit us — a group of more experienced grad students, along with us charged-up UGs, could have hastened the lengthy process of troubleshooting our protocols, saving us precious time. Research requires both innovation and experience and the latter we lacked.
Overall, the experience was extremely valuable, not only in enabling IISc to put out better iGEM teams in the years to come but also in providing us undergrads a taste of all aspects of research, not limited to the science of it.
Prabaha Gangopadhyay is an undergraduate from Indian Institute of Science (IISc), Bangalore, India. Year: 3rd, Major: Biology This is what he has to say “I like learning about mechanisms underlying the existence of life. I find myself comfortable in the overlap of theoretical and experimental biology, because of the extreme interdisciplinary nature of the area, and being at IISc has allowed me to explore it. I am interested in doing my final year project, and eventually my PhD, in Neuroscience. Other than science, I love literature, classical music, and, like any other undergrad, food!”