Looking Down a Microscope and Seeing Discoveries Happen

Andy Russell is a PhD Student in the Voet, Lawniczak, and Billker groups at the Sanger Institute, studying cancer and malaria. He recently completed his PhD and will graduate this summer.

Interviewed by Catriona Clarke, Social Media & Internal Communications Adviser, Wellcome Sanger Institute

Tell us about your work in up to 10 words

I design and apply single-cell sequencing technologies

How has your work been affected by COVID-19?

COVID-19 has undoubtedly affected mine (and everyone’s) life over the past year. The positive effect was that it forced me to work in my room every day on my thesis, without the usual social distractions. I also had to do my viva from my bedroom, which is definitely not how I envisaged the conclusion of the past four years of work. I did plan on doing some more wet-lab work for an extra chapter in my thesis but had to drop this when the Sanger shut down – in the end I restructured the thesis and added in some data that I had not analysed before and it worked out as I passed without any corrections. 

What is the most overused word/phrase in your lab?

Single-cell. It’s the bedrock of what we do in the lab. We think about the cell as having different layers or components, such as DNA (where information is stored), RNA, proteins, and other components. What we try to do is think about how we can profile each of those layers individually, but also how we can design technologies that can profile multiple layers from the same single cell to reveal more about what the cell is and what it’s doing.

Describe the Sanger Institute in up to 10 words

Friendly. Stimulating. Collaborative. Cutting-edge. Interesting. “Dark” also comes to mind, purely because of the winters here, where most of your time outside is during sunset.

Why did you become a scientist?

I was initially very interested in cancer; everyone is exposed to it in some way and I lost someone very close to me. I was still quite young, and at the time I started learning more about how the human body works and understanding what cancer actually is. I thought by understanding it and building on that knowledge, maybe I could do something to prolong the lifespan of cancer patients, or quality of life at least. That was why I decided to do a degree in biochemistry.

I was lucky enough to have really great mentors during my undergrad, and spent two  summers in labs at the Institute of Cancer Research. Chris Bakal took me on as a summer student, which was a bit of a risk as a first-year undergrad, but he was really supportive of me, and continues to be a valuable mentor.

Jane Mellor was one of my undergrad professors, and I worked in her lab during my Masters project in my fourth year of university. She really inspired me. She is a very impressive scientist, and that time cemented my desire to work in labs.

Then I applied to do a PhD at Sanger! The reasons why I want to be a scientist are still evolving, and I’ve now come full circle and am working in cancer research again, after having worked on other things. Ultimately, wanting to make human lives better for longer is why I do what I do.

Who is your science hero?

Jane Mellor and Chris Bakal, who I’ve already mentioned, are some of my heroes. Possibly because they’re tangible heroes to me, having worked with them both.

I’ve been lucky enough to meet Alex Shalek (a PI at MIT, working on new approaches to discovering cellular and molecular features in human tissues) and Aviv Regev (co-founder of the Human Cell Atlas, now Executive VP of Genentech), who are both heroes to me too. Aviv is an amazing scientist, she produces an incredible amount of work, often with innovative and inspiring approaches.

What is the most exciting development in your field from the last 10 years?

My field only came into existence around 11 years ago, with the first single-cell RNA-seq paper published in 2009. Single-cell technologies allow us to capture and measure various molecular components within a single cell. One of the most studied components is RNA, which is essentially a proxy for the identity of a cell. By measuring RNA and other molecular components at this unprecedented resolution, we can identify how cells vary between each other in a population. This is particularly powerful if we capture lots of single cells that as a population are undergoing a dynamic process, i.e. changing in time. This is because each cell can be thought of as a time point, and therefore the temporal resolution we can achieve is essentially dictated only by the number of cells we capture. The application of microfluidic technologies to biology was a moment when biology met engineering, this has enabled us to do single-cell experiments at scale.

What is the most surprising discovery you have made?

We wanted to know how malaria parasites make the decision to change from the asexual replicative form in the blood into gametocytes – the stage in the malaria parasite’s life cycle in which it can be taken up by the mosquito. We also wanted to discover how the parasite determines which sex to become once it has made this decision. We used a combination of single-cell RNA-seq and single-gene-knock-out mutants from the PlasmoGEM resource to identify many genes that were previously unknown to participate in this process. The identification of these genes may lead to the development of specific transmission-blocking strategies against them, which could contribute to the elimination of malaria. Our paper on this will hopefully come out early this year.

For me, the best surprises are when I look down a microscope and see it happen, because seeing is believing.

If you could time travel to any period in history, which would you pick?

I’d go forwards – I’d like to go 100-200 years in the future and see if we’ve managed to solve the climate crisis.

Or I’d love to go to the 1960s for the music – rock and pop and jazz – there was so much going on. And it was maybe a more hopeful time.

If you were omnipotent for the day, what is the first thing you would do?

I think climate change underpins many of humanity’s challenges for the next century and so I would like to solve this, but in a way that humans do not just go and do it all over again. Once that is done, if I still have time, I would probably work on fellowship applications for my future research direction. Then, I would be tempted to go on a run to get a new 5km personal best. But maybe I’d just put my feet up, because I feel like all my future runs that aim to beat my personal best would be pretty demoralising from then on.