Star Scientist of the Month - Dr Meghna Sobti

"I love everything about science! It’s a lot of hard work but when you finally get there, it’s the most amazing feeling."

22 June 2021

From a curious school student to an accomplished scientist, June's Star Scientist, Dr Meghna Sobti, shares the story of her lifelong love of science, its challenges, and the gains she's made in the field of structural biology.

Congratulations Meghna for your nomination as Star Scientist! You’ve been at the Institute for 12 years, and been able to work with different labs, tell me a little about your time so far at the Victor Chang Cardiac Research Institute?

Thanks, I am very excited and honoured to be nominated! I joined the Institute in 2008 as a Post Doc in Prof Thomas Preiss’s lab. In 2010, I moved on to work with Dr Daniela Stock for a wonderful six years, before joining Dr Nicola Smith’s lab for a couple of years. Since 2018, I’ve been with Dr Alastair Stewart, who heads the Structural Biology Laboratory here.

Sitting in that same seat for the past 12 years, I have witnessed a lot of changes and immensely enjoyed the time working at the Institute. The institute offers a wonderful support system, starting from Jason and Bob, HR, IT, engineering, my peers and everybody else. I live an hour away from the institute so to make that commute every day, you’ve got to love where you work.

What is your role within the Structural Biology Lab?

I study 3D structures of proteins using a technique termed cryo-electron microscopy. I use an instrument called an electron microscope, which is an incredible piece of equipment that allows us to understand protein function by imaging them with unprecedented detail.

The Victor Chang Cardiac Research Institute's Innovation Centre recently purchased and installed an electron microscope at UNSW. There are still only a few of these microscopes in Australia, so we are very fortunate to have quick and easy access to the microscope for our research.

I was lucky enough to be trained on these electron microscopes by FEI, the company that manufactures these instruments, as well as some of the experts in the field at Oregon Health and Science University, Oregon, USA. This training allowed me to not only use the instrument for my own research, but also train other local users.

Was it a challenge to learn how to use the microscope?

The microscope is pretty complicated so there were several aspects of learning to use the instrument! The initial training included about a month of online learning with understanding of theory and about 60 hours of videos to watch and then a month of hands-on learning in Oregon with the specialists. I was away from my family for over a month, especially my daughter who was seven years old at the time. I would say it was challenging but also very exciting and lots of fun to learn a new technique.

What does the Structural Biology Lab use the cryo-electron microscope for?

Our lab mainly works on protein complexes called ATPases, that convert energy from the food you eat into the energy currency that the body can use. They are like little energy-generating machines that are found in all cells, starting from bacteria to humans. We use cryo-Electron Microscopy to study the detailed structure of the protein complex which in turn helps us to understand how the machine functions.

Once we understand their fundamental biology, we can start thinking about what happens to the machine when things go wrong. For example, in the genetic disorder Leigh’s syndrome, where mutations in the machine can lead to impaired function and cell death due to the decrease in available energy. We can also use our knowledge to understand compounds that interfere with energy production in bacteria, producing novel antibiotics to use in the fight against antimicrobial resistance.

We have published several papers that highlight the inner workings of the molecular machine from bacteria. The most recent one published in Nature Communications describes the importance of flexibility within the protein complex that allows the motor to function efficiently.

We also collaborate with research groups from the Garvan Institute, the University of Sydney and the University of Tokyo, for many different projects using the electron microscope. The project with the University of Sydney described the location of the chloride channel in glutamate channels, which is important for nerve function and the collaboration with the Garvan Institute showed how therapeutic antibodies were able to interfere with SARS-CoV-2 infection.

What’s the proudest moment you have had throughout the process of learning and setting up the microscope?

My proudest moment was when we solved the first structure of the entire ATPase complex. We had been working on this complex for a very long time. I had spent a good five years trying to get it to work with lots of hurdles, like travelling to Singapore every six months with frozen samples because we didn’t have a microscope in Australia. I clearly remember that instant when we all first saw the structure of the complete motor on the computer screen; it was just an incredible moment.

And now after all that hard work, we have our own microscope to work on that is just 10 minutes’ drive away. We also have the expertise to carry out our own experiments; it is really been a game-changer.

What is it you love so much about science?

Oh, everything! The process of finding a question that you would like to answer, the challenges of trying to understand the problem at hand, the methods of solving the mystery, and the thrill that goes along with it. It’s a lot of hard work and only one in every few experiments will actually work, but when you finally get there, it’s the most amazing feeling. There is continuous learning and growing when you are a scientist. I absolutely enjoy it, the lab is my happy place, I can’t see myself doing anything else.

Has a career in science always been the goal for you?

I have always loved science! I remember when I was in school in India, we were driving through the outskirts of the city along a curving road and there was this huge, beautiful building. I looked up at it and wondered what it was and on the front of the building, it said, ‘International Centre for Genetic Engineering and Biotechnology,’ I told myself that day that I’m going to work there. I went home and researched what I needed to do to achieve my goal. I did my degrees and I ended up working at that exact Institute for seven years before I moved to Australia.

That’s a beautiful story. Do you miss India?

Yes, very much. I’m from Delhi and all my family, including my parents, are still in India. I normally try to go home at least once a year, but since COVID I haven’t been able to do that which is not easy in such difficult times.

I moved from India in 2005 to do my PhD at Macquarie University; after that I started working at the Institute and started my family here. Australia is home for us now. Hopefully, life will return to pre-COVID times soon and I can travel back to see my family.

Do you think your daughter might be interested in science?

Science is all around us, it’s hard not to like it. She does ask a lot of questions and likes to find the answers to them. I recently bought her a book about DNA because she asks me every day when I pick her up from school 'What did you do today?'. It’s tough to explain it to her but she’s only 11, so I bought her this book, so she can understand what I do at work.

Tell me a little more about what life is like for you outside of work?

I’m a very creative person and my friends call me “a scientist with a paintbrush”! I love to sketch; my specialisation is black and white art with pen. I sketch portraits that capture expressions as well as more structured art forms like zentangles and mandalas. I have exhibited my artwork both in India as well as at Tap Gallery in Darlinghurst. Besides that, I like to do patchwork to create quilts and bake beautiful cakes. I often run craft stalls in my daughter’s school fete where I sell handmade things to raise money for the school. I strongly believe in the power of creativity to both stimulate and calm your mind at the same time.

I also love plants, growing vegetables, and gardening. We have an enormous mulberry tree in our backyard. The month of September is when it fruits, we call it the mulberry month. All our friends and lab members get involved and we all pick fruit and make jams and pies. James Walshe in the lab made wine with the mulberries last year; it’s called Sobti Family Vineyard Vintage 2020. We aren’t allowed to open it just yet, but it'll be very exciting to try when we can!

What are your next steps? What are you looking forward to?

There are a lot of good things to look forward to and so many possibilities now we have the microscope and an accessible established technique.

There are some papers in the pipeline that will further enhance our understanding of the ATPase complex. I am starting to move towards translational research and start applying the structural and functional knowledge that we have gained so far. I am working on a series of venom peptides from snakes and spiders that inhibit the ATPase protein complex we are working with. We want to try and understand the difference between how the peptides bind to bacterial and mammalian systems so that we can develop these as novel anti-microbial agents.

Lastly, any advice for budding scientists?

In my opinion, a few essential traits are required to be a scientist; a lot of patience, persistence, and resilience to face the challenges and keep going, inquisitiveness to be able to ask questions, creativity to able to think outside the box, observation, and critical thinking to be able to analyse. Last but not least, an absolute love for science and don’t forget to have fun along the way!