In October’s blog post, we feature an interview with Dr. Vijay Rajagopal, Senior Lecturer of Biomedical Engineering, The University of Melbourne.

Vijay Rajagopal

When did you first become interested in mathematics and biology?

Two major things happened to me that drove me to where I am with mathematics and biology today:

I remember to this day that I was sitting in a first year Engineering Mathematics class and my future Ph.D. supervisor told us that he and his team had worked out that you only need 12 eigenvectors and eigenvalues to describe facial expressions. It blew my mind that maths could be used to describe and understand the human body. An interesting side note: that work was led by a Ph.D. student who much later became an Oscar Award winner for his animation work in movies like Spiderman.

The second time my mind was blown was when I read David Goodsell’s The Machinery of Life in the midst of writing my Ph.D. thesis on breast tissue biomechanics. I had never studied biology in high school and this book just transformed my naiive understanding of biology and cells at the time.

These two events led me into a career that spans mathematical modelling, bioengineering, and cell biology.

Was the decision to do a Ph.D. an obvious and easy choice?

I was not sure I wanted to do a Ph.D. I thought that I would just get a job. But every now and then I’d hear my dad or one of the professors tell me that I should think about a Ph.D. I’d often shrug at the suggestion. But towards the end of my 4 year Bachelor of Engineering degree, the time had come to make a decision. I looked up all the exciting jobs that I wanted to do, and they showed that I needed a Ph.D. in Bioengineering. I applied for a Ph.D. scholarship but also gave myself one final test: I applied and got a job in a software engineering firm, which I then declined. This gave me the confidence that I would have no regrets, and so I delved into a Ph.D.

How did you come to run your own group?

When I finished my Ph.D. I knew I wanted to work on cell biology. At the time, electron tomography was the latest new advance in 3D cell imaging. I wanted to visualise the 3D architecture inside cardiomyocytes, how they change in disease, and what these changes mean for heart function. So I shifted my postdoc career into mathematical and computational modelling cardiomyocytes. I was awarded an early career research grant to pursue my research interests. Through my research network I then moved to Singapore to learn about microfluidics and 3D cell migration. Through these experiences I cemented a vision to create spatially detailed and biophysically accurate computational models of cells that could be applied in basic science, drug discovery, and clinical applicaitons. I was then recruited by a colleague and mentor in Melbourne to establish my own research group.

Through all of this I am grateful to my mentors and funding agencies who supported my research vision and passion.

What are your main research questions and why are they interesting?

How does the heart grow? Our hearts grow from the size of a walnut to the size of our fist from birth into adulthood. This growth helps to sustain a force of contraction that supplies blood to our bodies. The heart also grows in disease conditions like hypertension but the structure and the function of the heart is compromised. Heart growth is fundamentally about the growth of individual cardiac cells that make up the heart. In my research group, we are focused on how chemical and mechanical cues govern gene transcription for heart growth (called hypertrophy). Besides chemical and mechanical signals, there is increasing evidence that the spatial organisation of signaling proteins within the cell play an important role in regulating heart growth. We are creating mathematical and computational models of cardiac cells to investigate these questions. Our aim is to apply our experimentally validated models to discovering drug targets for heart disease that would help to reverse disease related heart growth. There may be applications of our model in clinical diagnosis and even bio printing cardiac tissues in the future.

What mathematical equations do we need to describe, model, and predict mitochondria dynamics and their impact on bioenergetics? Mitochondria provide the energy our cells need to sustain life. Over the last 5 years we have seen some exciting new data illustrating that mitochondria form networks that are dynamic and seem to adapt to the cell’s energy needs. Uncovering the principles of mitochondria organisation and function will help us find mechanistic drug targets related to mitochondria and bioenergetics to treat heart disease, neurodegenerative diseases, and more.

A third research question is a broader question within the lab within which the above two questions reside. How does the cell’s internal architecture, the sub-cellular organisation of organelles, affect cell and tissue function? For a long time, mathematical biology and systems biology has viewed cells as bags of chemicals. While this is certainly a good approximation that enables us to describe and predict large-scale chemical interactions, we are yet to understand the hidden role of cell architecture. We believe that the architecture itself defines signalling cross-talk because many types of information exchange happen at the intersection of sub cellular structures. For example, apoptosis is regulated at the interface of the ER and mitochondria via calcium.

What makes you passionate about your work?

Cells are just so cooool! But seriously, the complexity of cell biology and the fact that computational modelling can help you dissect this complexity really satisfies me. Over time I have been fortunate to find collaborators and mentors in physiology and molecular biology who enhance my group’s work. Working with them on big questions to advance scientific knowledge and improve health outcomes makes this job exciting and fun.

What is a typical work day/week like?

A typical work day for me right now is to help 3 students finish their Ph.D. I am writing a review on 3D cell modelling that has given me the opportunity to think about where the research needs to go. I have a couple of papers from students that need to be reviewed and sent off. I am also interviewing people to fill positions for Ph.Ds in my lab.

Do you have any advice for someone considering a career in mathematical biology?

Your research environment is very important. This includes having a mentor who knows the value of your work. It also includes the types of experimental work going on in your environment. There should be experimental work that enables your mathematical biology modelling. Hopefully there are enough projects going on at the interface of biology and math biology that you won’t have to convince someone in that environment for collaboration. If you do find yourself in an environment where there is very little of what you need going on, don’t worry. Find your partners in crime wherever they may be and create your virtual environment. You can make it work.

The best collaborations are with people who you just enjoy having a chat with.

Never lose sight of writing papers or contributing to them. Grants are not in your control but finding collaborators, doing deep work, and writing them into papers are in your control. With mathematical biology we have an advantage of being able to do work at relatively lower cost to pure experimental science. Keep chipping away at the fundamentals of doing good science with good people and publishing them in good journals.

What do you like to do in your spare time outside of work?

In a parallel life I wish I could be a standup comedian. I dabbled in it for 2 years at the start of my postdoc career but realised that I would need to dedicate to it the level of focus that I need to do for science. So, I just write little jokes on my Facebook profile status update to keep me entertained. Here’s one that I posted recently:

“My robot vacuum cleaner, iRoomba is so thorough…ly dumb. Not only does it bang against walls to find its way around, today it tried to vacuum my daughter’s doll house! Even the doll slapped its forehead in disappointment.”

I also love hanging out with my two kids and partner as they help me gain new experiences in life. I have a small goldfish aquarium and I sometimes watch Bharathnatyam dancing on YouTube. Two things that I would never have been interested in before kids.