Professor Muzlifah Haniffa works on the Human Cell Atlas initiative to characterise every cell type in the human body. Like so many scientists over the last 12 months, her team has turned their attention to COVID. Working with colleagues around the world, she is uncovering how the virus enters and interacts with our cells.
We spoke about changing directions to work on COVID, and what is needed to achieve large-scale science.
“Think of what it takes to build something like the Burj Khalifa – the world’s tallest building,” says Muzlifah Haniffa, a Professor of dermatology at the University of Newcastle and honorary faculty at the Wellcome Sanger Institute. “Skyscrapers need architects, planners, electricians, glaziers - there are probably hundreds of types of specialists. If you want to achieve something major in science it’s exactly the same. You need many different specialists. The whole is greater than the sum of its parts.”
“In the Human Cell Atlas [HCA] there is a whole range of expertise. You need the genomics and computational experts. There's engineering in terms of how you store the data, then there is imaging expertise, clinicians, and more. No single group could deliver the HCA alone.”
Tell us about moving the HCA to work on COVID
“It felt very natural to me to work on COVID. There wasn’t anything new we needed to do; we were supple enough to pivot to a new area of study.”
“When the COVID pandemic descended on us, you could see how research changed. A lot of groups have come together to work collectively, otherwise the progress would have been just too slow.”
“As the HCA, we were already set up to work communally. Research infrastructure, collaborations, material transfer agreements and open-access websites to share data were in place. Our first data on COVID was added after just a couple of months of research.”
Some of the group’s recent research is on mouth and salivary gland cells – showing the specific cell types that the SARS-CoV-2 virus can infect1. Their work sheds light on how the virus might cause a loss of taste in some patients. The findings also show how the virus may travel in saliva, from the mouth to other parts of the body, such as the gut, or between people.
Other researchers in the HCA Consortium have looked at how the virus interacts with cells in the lungs and airways2. Muzlifah has also been part of studies into the immune response to COVID3.
“To study the immune response to COVID, we needed experts in every single type of white blood cell – neutrophils, B cells, dendritic cells and so on. It was a real divide and conquer effort.
“Having multiple groups meant we could work in parallel - different teams assessing different cell types. It also meant we had enough samples to meaningfully compare our measurements. We standardised our laboratory processes as much as possible – from reagents to protocols. Standardising everything meant that the datasets were easy to integrate. Instead of my team looking at ~50 patients in Newcastle, someone else looking at ~60 in Cambridge and London – we had 130 patients by pooling data from all sites. Immediately we had the statistical power we needed to detect links between cell types and disease severity.”
How do you acknowledge so many people being involved in a project?
“Science like this is not led by one person. We need to acknowledge whole teams. It’s only one piece of the puzzle, but the position someone appears on a list of authors on a scientific publication matters – it can influence future funding applications and career prospects.”
“Having just one or two lead authors is traditionally how scientific papers are written. This means credit is attributed to very few and may even discourage team science. I think we should consider strategies that gives credit to everyone who contributed to the research. In our latest publication, we have eight joint lead authors and eight joint senior researchers listed.”
What else needs to be done to enable large-team science?
“There are so many things to consider. Paperwork and administration shouldn’t be so cumbersome that is puts someone off collaborating. Material transfer agreements that allow samples to be moved between locations are an area that needs to be streamlined.”
“Research institutes and universities need to provide support, reassurance and facilitation for collaborating. For me, working this way has been a big lesson in research culture. Working where you have company, and colleagues to share and discuss results with, is beneficial. In terms of leadership, there isn’t a vertical line with someone at the top - everyone is equal. I think that has really helped us because it meant that everybody realised they were important, and everybody feels valued. Working like that requires a certain code of conduct and there are a lot of things in the background including trust and respect that you have to get right. You want to nurture an environment where everybody can work together.”
“Beyond institutes, funders and peer reviewers need to recognise that there is nothing lost by working together. We need to think about how to reward and incentivise team science so that more people want to do it. How do we help researchers see that it is far better for their science, and for themselves?”
Do you think this kind of teamwork is the future of medical research?
“Absolutely. It makes people think differently about how science should be done, and exposes them to a completely different way of doing things. You can learn so much from other disciplines. Knowing that you have a safe and secure environment where you're rewarded for sharing is so important.”
“I’ve been working in what I call, ‘the dream team’. When you're part of a team that you feel proud of, you can achieve just about anything.”