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Benjamin Murrell interview – Studying antibody responses to viruses

Benjamin Murrell has been awarded the 2022 The Svedberg Prize. Since 2018, he is an Assistant Professor at the Department of Microbiology, Tumor and Cell Biology, MTC, at Karolinska Institutet, and a central aim of his research is to understand antibody responses to viruses. When the pandemic began, the focus of his lab quickly switched from HIV to the coronavirus SARS-CoV-2.

Benjamin Murrell
Photo: Karolinska Institutet

– We are borrowing methods from HIV research and applying them to SARS-CoV-2. SARS-CoV-2 is an important global problem, but it is also a fascinating model system, and I think we’re going to learn general lessons that are relevant for other viruses as well.

The lab is currently working with assays to identify and characterize so-called cross-neutralizing antibodies – antibodies that can neutralize multiple diverse SARS-CoV-2 variants.

– Compared to HIV, the epitopes on SARS-CoV-2 that are commonly targeted by neutralizing antibodies are confined to a far more limited region of the envelope trimer, in and around the region that binds to the host receptor. This means immune escape mutations on SARS-CoV-2 tend to cluster in this area, but this phenomenon also allows us to come up with ways to narrow down our search for useful antibodies.

Another recent focus area of Benjamin Murrell’s lab are nanobodies – antibody fragments that occur in some animals, such as camels, llamas, and alpacas.

– Nanobodies are simpler molecules than antibodies, and more amenable to high-throughput discovery strategies. Together with a neighboring lab, we discovered a SARS-CoV-2 neutralizing nanobody in early 2020 from an alpaca that we immunized with SARS-CoV-2 antigens. We also recently published two more SARS-CoV-2 nanobody papers, describing a second generation of broader and more potent nanobodies.

Although nanobodies have promising traits, they come with a few challenges.

– Conventional antibodies have established track records as therapeutics but, when it comes to nanobodies, fewer clinical studies have been conducted.

Benjamin’s lab was on the news when the omicron variant of SARS-CoV-2 started spreading.

– We released very early data about how omicron evades our antibody responses, only 13 days after the variant was first reported. We showed that, in cohorts where people had been exposed to the spike protein multiple times – through vaccination or infection – then cross-neutralization of omicron was better than expected.

Benjamin Murrell’s background is in computational science. He did his PhD in computer science at the University of Stellenbosch, South Africa. This was followed by postdoctoral studies in South Africa and then the US, where he was introduced to experimental science. This combination of skills comes in handy in the research that he does today, says Benjamin Murrell.

– I always strive for an “end-to-end” methodological understanding of a research problem. This helps the computational research be more biologically grounded, but also helps us design experimental approaches that can take maximal advantage of downstream analytics.

What does the The Svedberg prize mean to you?

– This award means a lot for me. On a personal level, it’s my first prize of this kind. On a practical level, when you move to a new country as a researcher, it’s also helpful to be recognized, and have people in neighboring fields know who you are and what your lab works on. I’m also looking forward to the Sweprot meeting, where I will be able to build connections with people that I don’t normally meet.

Benjamin Murrell has been awarded with the 2022 The Svedberg Prize. He will present his research at the 25th Swedish Conference on Macromolecular Structure and Function (Sweprot) in Tällberg, on the 17-20 June 2022. Read a press release here: The Svedberg Prize 2022 to Benjamin Murrell, Karolinska Institutet – Svenska Kemisamfundet

Text: Erika Lindbom Sierakowiak