Nitin Baliga, PhD

How do you combine your two degrees in microbiology and marine biotechnology when approaching research, especially pertaining to tuberculosis?

My career wasn’t a straight path. I don’t think anyone else’s career is either.

When I got my degrees, I didn’t know what I was going to be working on down the road, so tuberculosis was not something I had planned on at that time. Even how I got to microbiology was a series of unplanned events, including some outside of my control. I was unable to get into medical school for a variety of reasons, so I decided to go to microbiology because that was the next best option. To be honest, for the longest time, I didn’t really know what I was going to do. It wasn’t even until my second or third year of college when I started to enjoy microbiology. 

I finished my bachelor’s but I didn’t know what to do next. In India, there was a national entrance exam, so anyone who wanted to go into higher studies would have to go through this testing system. If you passed, you got randomly assigned to one of eight universities, and based on what programs they have, you decided to join or try something else. I went into marine biotechnology because that’s what was offered at my university, not because I planned to. 

Even after that, my PhD was in a different area, so that’s what I meant when I said that my career wasn’t a straight path. I tried a lot of things. In retrospect, that was a good thing. Eventually, I realized what I’m good at, what I enjoy doing, and what I want to invest time in. Tuberculosis was a conscious selection much, much later.

Don’t be surprised if your career unfolds in a similar way. That’s a good thing. If you knew exactly what you were going to do, you’d get bored very quickly. It’s good to have surprises along the way; you get to try different things. There might be things you’d never thought of that you encounter. If you’re receptive, it will work out for you.

One of the things that ISB emphasizes is having scientists from multiple disciplines work together. How do you make sure multiple disciplines are interacting in your lab, and could you give us an example of this collaboration happening right now?

Research in any lab typically takes a similar form but it’s more exaggerated in systems biology, where we ask big questions. 

For example, we might ask a question regarding drug resistance in TB. Primarily, we want to understand how drug resistance evolves, and we want to develop new drugs to fight resistance. When you start breaking that question apart into actionable hypotheses and approaches to address those hypotheses, you quickly realize that you need to do all kinds of measurements. You need technologies to be able to culture the microbe in different contexts. This approach requires someone with strong microbiology skills. If you need to engineer reactors, you need an engineer who can design and build one of these reactor systems. You’ll need to profile the pathogen with multi-omics technology, so you need to sequence DNA and RNA; you need to do protein analysis. Soon, you’re faced with large amounts of data. To analyze that data, you need people who understand computational biology and who have good statistical and math backgrounds, so you need a different set of skills there. You analyze the data, you build models, and from the models you build new hypotheses, and to test the models you need someone with good microbiology skills to perturb the pathogen. As you go through that cycle, you see that different people with different skill sets are needed to go from a question to a hypothesis to doing an experiment to modeling data and so on. Systems science organically brings together people with different skill sets.

Nowadays, every person has multiple skill sets. Your training is going to be very different from my training. But when you get out into the workforce, you’ll find that having a generalized knowledge of skills is good because you understand concepts from different disciplines. However, you still need people with deep expertise in certain domain areas to come together. The way I built it in my lab, part of it was need-based, and as we became more conversant with what was required, we could then plan ahead and say, “Ok, we need to hire someone with this skill set so we can take on problems of this type.”

In general, you need a diverse skill set which gives you the capability to take on different types of projects. But when you write for funding, you have to give them a clear scope of the project: what you want to do, what skill sets are required, who on your team has those skill sets. As a lab becomes more established, you have in-house capabilities that allow you to do a lot of things. 

What was your most valuable mistake or failure that you had during your scientific career?

Mistakes and failures are two different things. I won’t say any of my failures was a mistake. That’s just a mindset - to look back and constructively evaluate what influenced your career trajectory. When I do that, I find that I stumbled upon many opportunities. That was the best I could do at the time. I don’t think it was anyone’s mistake, but I did the best with whatever opportunities were presented to me. 

The worst that could happen is I could fail, and if I fail, I could just stand up and go in a different direction.

I did take risks. I think that everyone needs to do things that are not the most comfortable. For example, I tried to get into an area of research soon after my master’s program as a part of my PhD research work; I started working on malaria. I explicitly decided not to apply to universities outside of India. In retrospect, one could say that was a mistake, but I would say I learned a lot, because I tried to do research in that environment [in India] and came to realize that India was heavily resource limited. 

Besides, malaria was not a topic of great interest to me. It was of interest but it didn’t align with my skill set or the skill set I wanted to acquire at the time. After a year and a half, I decided to do something else, so I switched back into microbiology. I was able to recognize how much I was interested in microbiology, which I might not have realized had I continued down the microbiology path. But it also made me fearless when it came to trying things. 

Since then, I haven’t been afraid to go into new areas of research. The worst that could happen is I could fail, and if I fail, I could just stand up and go in a different direction. I think that mindset has to be there for anyone who is a student of anything, and you have to be a student of everything and anything throughout your career.

If you keep asking leading-edge questions, you’re always pushing the frontier of what we can do. That’s the fun part. You’re always pushing yourself to go into an uncomfortable zone. You’re not just resting on your previous laurels. 

What do you think are barriers to innovation that were present in India?

You can say there was a lack of innovative culture, not because people weren’t innovative, but because there weren’t enough resources or infrastructure to support innovation. Innovation requires people with great ideas and infrastructure to help them execute those ideas. A place like ISB supports multidisciplinary research and brings many different people into one building, which is difficult to do in a department of mathematics or chemistry. Even if you have a good idea, a certain environment or institution that doesn’t support those ideas could be a big hurdle. 

Also, the type of funding support you get can influence how much you can try risky things. Historically, and even now, NIH (National Institute of Health) and NSF (National Science Foundation) have funding mechanisms that are very conservative. When you apply for funding, you have to ask for things that will most likely work. When you propose such things, you’re very likely to get funding. But if you do exactly what is outlined in the proposal, then you’ll end up doing lackluster, not innovative, science. You need to learn how to convince study panels to fund your research, then how to use that money to address all the aims you proposed while also doing leading-edge and high-risk projects. 

When you came to the US from India, did you want to build an environment for innovation in addition to chasing more specific research topics?

At the time, I didn’t have this broad vision of driving innovation. For me at the time, my priority was my own education and getting sufficient resources to be engaged in leading-edge research. I was still learning, I didn’t know what it meant to be innovative. I knew that where I was wasn’t innovative. I didn’t know what it would take to shift towards more innovation. 

Over the years, as I learned how research is done from people who are more experienced, I became more aware of what works and what doesn’t work in a lab. Over time, you build your own understanding of what an innovative environment looks like - they’re not all the same. You have to constantly think about what it means to innovate now. Biology was not an information science ten years ago; we didn’t have these big machines collecting large amounts of data, but now we do, so the innovation infrastructure had to evolve to bring in those technologies and people into the right space.

You learn best from other people who are on your team.

How did you learn to take advantage of the advancements in scientific technology since the conclusion of your schooling? 

Science will continue to move in ways that you cannot predict. One way to keep up with the changes is to take a sabbatical. Another way that I find to be more productive is to bring in people with that expertise and collaborate with them. That’s why team science becomes important; you learn best from other people who are on your team. When you’re at my stage in my career, you just need to listen. Through those interactions and reading appropriate literature, you can learn enough. You could not become a master with every new thing but you can certainly understand enough so that you can use it effectively. 

How do you see science communication growing and changing in the future, especially given the current social climate and disinformation circling in our society?

I know it can be discouraging to see the conversation threads about a politically charged issue. The thing to remember is that the internet has just given a platform for a lot of misinformed people to get together, share their ideas with each other, and get encouraged down the wrong path. But remember: There are a lot of people like you, who are taking the time to learn and think critically about an issue. The best weapon against disinformation is information. We have to get out there. Picking up an argument on an online thread is not productive; I came to that realization the hard way. 

The right way to deal with it is to get involved in a scalable platform for education and outreach. One of the ways that I helped with this is through ISB’s educational programs that benefit thousands of students and teachers. As students, I think you have to find mechanisms and efforts that can help you reach exponentially large numbers of people through structured interactions and focus on some of the foundational skills. It’s not giving the information to everyone, but teaching them how to get the right information.

Critical thinking is a foundational skill. If I tell you something, you should always look for orthogonal sources of evidence that support or refute that piece of information, look for (in)consistencies across independent sources that corroborate or disprove the authenticity of information. That is a very powerful weapon against disinformation. Fight disinformation in a way that doesn’t draw you down. Don’t argue with that one person who has put their head in the sand - why waste your time on something like that?

Do you have any ideas for how the education system can be destandardized to be more focused on individual development of critical thought?

I think the whole concept of project-based learning is the right idea. You have to start with the observations, hypotheses, or questions. When you see certain phenomena, you should be curious. If you ask the right question, then the learning process flows very well. You need some structured framework to know how to answer questions using authentic tools. That’s why you go to school - to work with professionals who have the expertise to direct your learning. To know how to do it yourself, you must have some kind of scaffold, which is why the education system is good, but it can be better: Everything should start with a problem and a question. You should be asking questions, which you follow up with experiments to test if you’re right or wrong. 

That’s why I said that failure is not a bad thing. You ask a question, you do experiments, you find your hypothesis was wrong - that’s not a failure. You’re finding out that a certain explanation is not fitting with the observation, so it’s pushing you in a different direction. That’s constructive. If you learn information this way, you’ll never forget it because you experience it first-hand. In our learning models at ISB, we want the students to get excited because then the brain becomes a sponge. 

What project in the Baliga Lab are you most interested in seeing the results for?

We’ve been trying to find a drug for tuberculosis for over a decade. There’s this new theory we’ve been working on: If you drug the networks that control how the organism responds to environmental change, you can have a system-wide effect to kill the organism. The pathogen can cloak itself, changing the cell wall to make it impenetrable, and it can keep changing. If your target genes control how the pathogen remodels its cell wall when it’s living in the host, then in essence, you are disabling its ability to change its armor. We’ve discovered a regulator that controls this remodeling process. We published a lot of papers on it and got a grant from the Gates foundation to find a drug that targets that regulator. In fact, another group has found that this regulator is the most vulnerable point for the pathogen. It looks very promising, but it’s also a very difficult target to drug. In the next year, I’m very curious to see if we can find a molecule that targets this regulator and proves to be effective in killing the pathogen. There’s still a long journey beyond that, too. Maybe it will happen in the next five years, but if it works out, it will be a very exciting thing for us.

This is a whole new venture for me because I’ve never done drug discovery before. Typically, a lab would just find a target and hand it over to a pharmaceutical company. However, no pharmaceutical company wants to make a drug for tuberculosis because the patients who need it are in the developing world and have pennies to pay for it, so there’s no monetary incentive. 

Know that even the most established scientists and researchers fall off because things don’t work out, but they’re resilient.

Anything you do can be fun at the beginning, but to do it right through the end, you will need to do a lot of hard work. While I encourage everyone to do multiple things, I also recommend not giving up after the first rough patch. Stick with it long enough to make sufficient progress and then change not because you hit a rough patch, but because you were happy with what you learned and you want to try something new. 

For me, maintaining motivation is about keeping the big vision. With the tuberculosis discovery, I know that the end of the journey is finding the drug. Just because this target turns out not to be the right one, it doesn’t mean we’ve failed; we’ve developed and learned a lot in the process. You need to focus on the details, but once in a while you need to step back. You need to enjoy small successes and be proud of your past accomplishments. You know you’re part of a team; lean on your collaborators to get comfort and support when needed. Know that even the most established scientists and researchers fall off because things don’t work out, but they’re resilient. They get up and continue the journey.