(Semi)speeding Towards Breakthroughs

Falling, getting up and rubbing the dust off our hands to making progress

This is an exciting time to be alive. For the first time ever, a book encoded in DNA is available for sale (and of course, BioCompute has pre-ordered a copy for ourselves).

Take a moment to let that sink in. DNA storage has finally (officially) moved from the domain of academic labs to a tangible product that consumers can access. And that’s a HUGE milestone.

Image Description: DNA book by Asimov Press in collaboration with a few DNA storage companies

Of course, the average consumer cannot read the DNA sequence within the comfort of their homes like they would a physical or a kindle version of the book. And that’s partly why we at BioCompute are so keen on building out the entire read-write-store-retrieve stack in a modular hardware, apart from the fact that a piece of hardware like this can significantly reduce the space and energy consumption of data centers.

Where are our experiments at?

1. Nanopore fabrication (to read DNA)

We have finally managed to get the circuit for dielectric breakdown up and running (a huge shoutout to everyone who helped us troubleshoot). We naively assumed that this means we can just insert our chip into the flow cell and make our pores.

But while attempting pore formation, we accidentally broke the screws of the cassette and spent a week trying to procure screws that match the dimensions. It didn’t help that we were attempting to do this while the rest of the world was taking time off to celebrate Christmas and New Year. Finally, Akanksha and Ajay made their way to SP road (nearly 18 km from our workspace, but dreaded because of the infamous Bangalore traffic) to get custom-made screws that fit into our flow cell.

Image Description: The notorious screws

Now that screws aren’t screwing us up anymore, we set out to break down some membranes. However, we are running into very high leakage currents which should ideally not happen in the kind of system we have set up.

Image Description: Our leakage current is 10x higher than what it should be to make pores

We are now in the process of troubleshooting this so that we can get to making pores and optimize the process to get to reasonable repeatability. We can then use these pores to read DNA. And we are hiring a full-time electronics engineer to accelerate progress, if you are excited about this do check it out and apply.

2. Enzyme synthesis (to edit DNA)

We came up with the sequence for an enzyme to edit DNA at the single nucleotide level, and have been working closely with a CRO to express and purify it so that we can determine the efficacy of the enzyme.

While the protein is being expressed fairly well in our expression systems, it unfortunately isn’t soluble enough for us to purify it (and we need to purify to be able to carry out experiments outside cells).

We are now attempting to express the protein in a very specific bacterial strain that is optimized for disulphide bonds to improve solubility. This is an important problem to solve, and also a very important piece of our IP as we take DNA storage to commercialization.

We look forward to chatting with enzyme engineers and protein biochemists to get their insights on optimizing the expression evaluation as well as optimizing the enzyme in the long run (thanks to Sujoy and Vaibhav for chatting with me in the last week).

3. I am attending the Accelerating Biology conference by the Centre for Development of Advanced Computing (CDAC) in Pune from 7-9 January (and writing this during the inaugural ceremony, because why not). I am excited to connect and chat with folks at the intersection of data and biology to gain insights and explore potential collaborations.

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A few things I have learnt from the last 6 months of being a full-time founder.

a. People are more generous than you think they are
The biggest learning has been the perspective altering (and hence a tad bit disappointing and a lot more humbling) realization that none of us can operate independently. This is starkly visible to you when you start building a company. At all points, you find that you need things that cannot be done in-house.

When you are trying to grapple with that fundamental truth and live with it, that’s also when you realize that people are more than willing to support. In the last few months alone, the number of people who have opened up their purses, homes, networks and calendars to help us is incredible. A lot of times these have been people who barely know us, but were fascinated by what we are building and stepped up. There are people who think of me when they come across a research paper, a blog article or a book, and then very generously send them across. I am incredibly grateful to these people and am trying to pay it forward as much as possible.

b. Building a company culture while optimizing for optimal outcomes (constrained by time and money) is hard.
It’s easy to be a rebel, but setting up systems that work (and dealing with other rebels) is a tough iterative process. I am still figuring out how this works.

c. A good Canon printer costs only INR 2,600 on Amazon
I have grown up believing that a printer is a super expensive purchase. I was pleasantly surprised when I found out what it costs today - perhaps the cost of printers themselves have come down, or our purchasing power has gone up. But anyways, I wouldn’t have checked if I hadn’t started a company.

d. Getting into a disciplined lifestyle is hard but is worth doing
Being regular to morning workouts, therapy sessions, and having a mostly fixed sleep schedule is helpful to gather and sustain energy for decision-making and then the drudgery of execution.

e. Looking for delights is a meaningful pursuit
Ross Gay’s conversation with Krista Tippet in this episode of ‘On Being’ and his book ‘The Book of Delights’ gently nudged me to actively look for delights in everyday life, and be generous with what you qualify as delights. Given how our brains are wired to pick out threats, being conscious about joy is perhaps the only way to invite it in. This practice has been extraordinarily valuable on days when it feels like BioCompute (the scope and scale and the everyday challenges) is crushing me.

f. Communities and supportive friendships are extraordinarily valuable
It takes a village to raise a company; more precisely a village of equally ambitious and irrationally optimistic folks. Finding them and hanging out with them keeps you going. I am finding and building my own Lunar Society (thanks Amruth for sharing this one, and excited for the community you are building out).

Building the Lunar Society