Researcher Spotlight: Dr Arun Shukla

Dr Arun Shukla is an assistant professor in the Department of Biological Sciences and Bioengineering, at the Indian Institute of Technology. His research focuses on the largest group of cell surface receptors and he hopes that understanding the atomic level structures of these receptors may in future help us design more effective drugs. Here Dr Shukla talks about how he came to be at the forefront of a new line of research in India…

What are you working on?

We are trying to understand how G Protein-Coupled Receptors (GPCRs) work. These receptors are the largest class of cell surface receptors in our body and they are targeted by about half of the currently prescribed medicines.

GPCRs control many physiological processes in our body such as blood pressure, heart beat, pain sensation and appetite – to name a few. Our primary focus is on obtaining atomic resolution information on selected GPCRs to decipher their activation and regulatory mechanisms.

We design and generate synthetic protein binders to stabilise these receptors in specific conformations so that we can trap these conformations by X-ray crystallography.

What does your average day involve?

The first thing I do after coming to the lab is to talk to my students and fellows, get updates on experiments, discuss and design the next steps and so on. Then, I talk to my lab manager and get updates on the status of various orders, visitors etc. Of course, on days when I have to teach a class in the afternoon, I work on slides and read about the topics that I am going to cover in the class.

I like to work on grants and papers in the afternoon and try to spend solid two-three hours if possible. As you can imagine, there are other commitments on some days such as different committee meetings, seminars etc. And yes, a couple of trips to coffee joint and checking emails every five minutes.

Why is your work important?

We believe that our work will not only reveal fundamental mechanistic insights in to very complicated cellular signalling events but it will also provide a framework for translational discoveries. Our research is directly relevant to a number of human diseases and the hope that perhaps our research findings in long run might help somebody, someday, somewhere, is what keeps us motivated and to keep going.

From the Indian science point of view, our work is likely to establish a new line of research in India i.e. Structural Biology of Membrane Proteins, GPCRs in particular. This is an incredibly challenging endeavour and has not received much attention in the Indian research community. Thanks to Wellcome Trust DBT India Alliance fellowship programs, this research domain is picking up some pace in the country.

What do you hope the impact of your work will be?

We hope that by understanding their atomic level structures, we will be better positioned to design drugs that will be more effective against various diseases and will have lesser side effects. Although our work primarily focuses on basic research, the potential outcomes have tremendous translational potential. 

How did you come to be working on this topic/in this field?

My lucky break in research came when Professor Rakesh Bhatnagar from Jawaharlal Nehru University (JNU) in New Delhi (India) arranged for me to do a summer research project during my MSc in Professor Shyamal Goswami’s laboratory. That is where I realised that research was my calling.

During my Masters in biotechnology, I started to learn about how critical membrane proteins – especially GPCRs – are for receiving diverse signals outside of the cells and communicating them across the membrane to inside of the cell. This got me fascinated with these incredible molecular machines and I developed a desire to understand their atomic details.

How has Wellcome funding helped you/your research/your career?

The kind of research we do is incredibly expensive and consumables-intensive. And, that perhaps applies to most research areas in life sciences, if not all. I feel very fortunate to have received the Intermediate Fellowship within a couple of months of landing in India. This meant that I don’t have to run after many different funding agencies to accumulate the quantum of funds that I would have liked to begin with.

Moreover, the flexibility to spend the funds as per the needs of the project and the timely release of funds are indeed a blessing. As the India Alliance fellowships are highly competitive, the prestige of being a fellow also has added advantage with respect to visibility in the science community.

What’s the most frequently asked question about your work?

I always talk about how many physiological and cellular functions are mediated by GPCRs. People often ask me how can they regulate so many things with extreme temporal and spatial precision in a very complex cellular context.

I wish that I knew the answer but that is what we are trying to figure out. The other question that I often get, especially from students, is how did I get a chance to work with three different Nobel Laureates during my Ph.D. and post-doctoral research? – I say, “I just got lucky”.

Which question about your work do you most dread – and why?

Nothing as such but sometimes, people ask me how closely X-ray snapshots represent the native structure of proteins in their natural environment. I do not think that anybody has a very good answer to that.

Tell us something about you that might surprise us…

When I was in college, I developed an interest in journalism and politics. I even considered a career in one of those professions. I wrote many small articles for national newspapers and magazines, and I also contested elections of the students union in college.

I guess writing research papers now satisfies my appetite for getting published and perhaps in future, I would be able to contribute in science policy decisions to my address my cravings for administration.

What keeps you awake at night?

Anticipating data that my students email me late at night, often past midnight. When I go home in the evening, I know what experiments were being run in the lab and which of them will be finished later in the night and yield some data. I have my smartphone under my pillow and when it beeps (indicating an incoming email), I just cannot resist checking it.

What’s the best piece of advice you’ve been given?

I guess, the advice given by my post-doctoral mentor, Professor Robert Lefkowitz (Nobel Prize, 2012). He used to say: “there are three keys to success in research, the first is focus, the second is focus and the third is focus”. Even now, I tune to one of his YouTube videos once in a while and hear him say this again.

The chain reaction question – posed by previous spotlit researcher, Dr Daniel Streicker, is this: If you had a time machine, what year would you travel to and why?

I would love to travel 20 years into the future and see how the projects that we worked on progressed over the years. Of course, I would be lot wiser when I return because I would know what did not work, and we could tweak the experiments accordingly.

If you’d like to read more about Dr Arun Shukla’s research, the following papers may be of interest: Methodological advances: the unsung heroes of the GPCR structural revolution and Visualization of arrestin recruitment by a G-protein-coupled receptor. You can also follow Dr Shukla on Twitter as @ArShukla.