From cancer, stem cells and organoids to COVID-19

In response to the current COVID-19 pandemic, many of our scientists have been redeployed. We spoke to these Sanger scientists, who are currently working on the effort to sequence samples of SARS-CoV-2 to track the spread of the disease.

Sanger Institute scientists (L-R) Charlotte Beaver, Katie Bellis, Luke Foulser, Adam Jackson, Rachel Nelson and Laura Letchford.

What is your day job at Sanger?

Luke Foulser: I’m a research assistant. I work on neural stem cells, culturing induced pluripotent stem cells so they can be differentiated into neurons, or neural stem cells. I work on the Deciphering Developmental Disorders Project.

Katie Bellis: I’m a lab manager and research assistant looking at the asymptomatic carriage of Staphylococcus aureus in healthy people. I work on the CARRIAGE Project, which is affiliated with HDR-UK, and am part of the Peacock Group at the University of Cambridge.

Charlotte Beaver: I’m normally a senior scientific manager, running two of our big cancer projects. We make 3D cell cultures (organoids) of patients’ cancer samples, and I also run a whole-genome CRISPR screening of cancer cells project to find potential new drug targets.

Laura Letchford: I’m a senior research assistant in the Cellular Generation and Phenotyping (CGaP) facility. I work on the organoid project that Charlotte mentioned, growing cancer organoids from patient samples.

Adam Jackson: I’m a research assistant in cancer research. I normally work with organoids.

Rachel Nelson: I’m head of CGaP. I go to a lot of meetings! And coordinate projects, manage budgets, capacity, that kind of thing.

Tell us about your involvement in the COVID-19 sequencing project

LF: I’ve been part of the team setting up the project; ordering equipment, liquid handling machines for sample preparation, and making sure everything is set up and ready to go. I’ve also been helping to set up the operating procedures for the project.

KB: I’ve been helping to set up the processes, and giving an infectious disease insight.

CB: I’m working with the teams receiving the positive COVID-19 samples, and helping out DNA pipelines, so the samples are ready for sequencing.

LL: I’ve been setting up lab protocols for receipt of samples, and working with our software developers on how best to record the samples we’ve received, before they go for sequencing.

AJ: I’m helping out in the initial set-up; trouble-shooting all the protocols so we’re as streamlined as possible

RN: I’m heading up the sampling team – helping understand the material that we’re going to receive, and how to process it to make it safe for DNA pipelines, so they can more easily plug the samples  straight in to the processes they are developing.

Why did you become a scientist?

LF: My interest was really the brain. I was originally interested in behaviour, and then as I went through my degree, I became more interested in the molecular side. The brain is so complex, and there’s so much we don’t know, so it’s incredibly interesting.

KB: It just kind of happened. At the end of sixth form, I either wanted to do history or biology at university, and on the day I had to submit my application the biology one was done, so that one got submitted. I like looking at big questions, and trying to gather evidence to get closer to the answers. I think that applies both to history and to science, it’s just the methods of gathering evidence that can differ! I did lab work in my summers and found that’s what I wanted to do.

CB: It seemed like the best thing for me to do. I’ve always liked science, and particularly in cell biology where you can actually watch cells under a microscope.

LL: I loved science at school, and just like knowing how things work. It seemed the obvious choice, because now I get to spend my life trying to work out how things work.

AJ: I liked biology lessons at school, and then after school I worked as a lab technician for a year. I really liked working in a lab, and so went to university after a year of that and the rest is history.

RN: It wasn’t intentional, I originally wanted to be an interior decorator or an architect. I then impulsively went into science, before becoming an aerobics instructor, then going back into science. I enjoy it, I’m good at it, and much better than I thought I would be.

Who is your science hero?

LF: I don’t actually know!

RN: Don’t be embarrassed, Luke, you can say me.

CB: I’d say Jennifer Doudna, she was one of the first researchers to use CRISPR technology, and saw the potential for its use in gene editing.

AJ: My biology teachers from school. Either Mr Barker or Mr Brown, they were really engaging and passionate about their subject. They spoke to us like we were adults, and didn’t patronise their students.

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

LF: Induced pluripotent stem cell (IPSC) culture. It’s changed the field completely, and it’s meant we don’t have to work on human embryos so much. You can take a sample from a patient, and then turn back time on those cells, so that they can become any cell type you want to study.

KB: Bacterial metagenomics technology has come on so far. We can look at populations of bacteria, rather than having to isolate them to get genome data. We’re still figuring out the applications of this, and there are hurdles in figuring out artefacts and applications, but the technology is tremendous, and the difference it will make over the next 10 years is very exciting.

CB: CRISPR technology has so many uses. We use it to knock out genes in cancers, and see which genes are essential for their survival. It’s such a powerful technology.

AJ: I’d also have to say CRISPR-Cas9 technology.

LL: It’s been around for ages, but being able to culture things in three dimensions has really taken off in the last 10 years. That’s how organoids work – and you can more closely recapitulate how cells grow in the body. Rather than being flat on a plate they can grow and communicate with each other like they would in the body.

RN: What’s so great about working at Sanger is that revolutionary science tends to come our way. Without CRISPR, organoids, IPSCs, my team wouldn’t exist. We specialise in genome research at scale, and what has allowed both my team, and Sanger in general to deliver to this remit is single-cell sequencing. It allows us to do both research at huge scale, but physically on a very small scale.

What is the most surprising discovery that you have made?

LF: That I can do this?!

KB: I don’t hate paperwork as much as I’d thought.

CB: I think having people who are really dedicated and driven to improving your processes delivers the best projects possible.

LL: When I was at school, my teacher told me I didn’t have a brain for science and that I couldn’t think outside the box. I’ve found that in certain scenarios, that doesn’t matter, and there’s still a job suited to everyone. It’s driven me to prove her wrong.

AJ: I think scientists in general surprised me. They’re not like the stereotypes you’d expect at school, the clipboard-wielding types obsessed with facts – they’re normal!

RN: I think it’s easy to forget, working in a core research group, that you’re also a part of much larger discoveries. I got into science to be a scientist, but have found more of an interest in project and process management. I’ve found that industries like car manufacture actually marries beautifully with scientific research, because if you use your tools well, you can deliver an awful lot of ground-breaking research within a short space of time and money.

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

LF: 50 years from now. I think we’re at a really critical period right now in terms of climate change, so I want to see what the future looks like.

KB: My instinct goes Tudor. I loved the history of that. But then you think about being a woman, and not a member of the nobility in that time, and it puts me off. And also there were no antibiotics, so maybe a post-antibiotic time.

CB: I also think Tudors, I want to see what the attraction of Henry VIII was. Also World War II, just because it was such an important time for women in science.

LL: In this current situation, where there are fewer cars on the road, it made me think about going to a time before cars existed. A simpler time.

AJ: I’d like to see before civilisation, but as long as I was only visiting.

RN: 1980s. Every time.

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

LF: It’d be fun to be invisible. It’d be fun to mess with people. In a nice way.

KB: I’d probably go crazy. I’d be paralysed by the power and never get round to doing anything worthwhile.

CB: I’d make calorie-free chocolate. Or make breeds of cats that are kittens forever.

LL: I’d definitely get a dog. But other than that I think, like Katie, I’d freeze!

AJ: I’d love to be able to click my fingers, and have something that works. Like a cure for something…

RN: …like to the current pandemic maybe?! I would revolutionise culture in science and the NHS. I think there’s too much pressure on publication to guarantee funding coming in, and the NHS has a similar mentality. It doesn’t lend itself to the best discoveries. I would change that so we’re able to come together to do what’s right. Especially now.

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