Prize winner paves the way for viral infection protection

“Given that my PhD research had serendipitously led me to working on this receptor, I was uniquely placed to get back into the lab and start testing the hypothesis” says James Daly, Winner of the Science & SciLifeLab Prize for Young Scientists ‘Cell & Molecular Biology’ category, about the idea that the SARS-CoV-2 Spike protein binds to Neuropilin-1.

When things like DNA, proteins, membranes and organelles – the fundamental components of molecular biology – entered James Daly’s studies he knew that biology and chemistry were going to be his focus from now on. He found it incredibly fascinating that everything around us largely boils down to the same molecular building blocks.

There is a hidden world of complexity and innovative evolution inside every cell, and there is still a seemingly infinite amount left to discover.

At 17, James wrote an essay on the potential use of gene therapy to correct genetic diseases like Cystic Fibrosis and Huntington’s disease. This experience of dissecting the available literature on a specific topic was the first time he really thought about a career as a researcher, and what ultimately led him to the University of Bristol to undertake a Biochemistry degree. That fascination remains to this day.

“The cellular processes that I studied during my PhD are happening in the yeast, in the air around you, in the plants outside, and in the cells throughout your body. There is a hidden world of complexity and innovative evolution inside every cell, and there is still a seemingly infinite amount left to discover” says James Daly.

James Daly’s PhD research focused on how cells sort through their parts, like a waste management facility, deciding which should be degraded and which should be recycled. This maintains a balance that protects against a range of diseases. The sorting is performed by microscopic molecular machines called protein complexes, with the endosomal network being a master controller of this delicate balance.

“I was led to my PhD research by a desire to connect my interests in these cell biological pathways from my degree with the clinical consequences that arise from their disruption, particularly with a focus on neurodegenerative diseases where endosomal network dysfunction leads to the propagation of pathogenic protein aggregates and neuronal cell death” says James Daly.

For the love of football
Growing up in the UK, football was always present. Now, either watching or playing, James finds it to be a good way to disconnect from research, and it allows him to refocus. One would think that James’ favorite team would be an English one, with the British Premier League next door – one of the best leagues in the world. It is, however, Valencia that he tries to see every chance he gets. That choice is not entirely random. James is half Spanish, with relatives in Valencia.

Given that my PhD research had serendipitously led me to working on this receptor, I was uniquely placed to get back into the lab and start testing the hypothesis.

The Fifa World Cup, or simply the World Cup, is the most prestigious competition for national football teams. It is played every four years, and is currently ongoing with both England and Spain qualified for the finals. The two teams can still face each other in the semi-finals, something James feels some level of conflict over. He does, however, seem quite diplomatic about the whole thing.

“I’ve been fortunate to see Spain win major competitions before – two Euro championships in 2008 and 2012 and a World Cup in 2010 – so it would be nice to see England finally win something in my lifetime instead!” says James Daly.

Locked down
When the COVID-19 pandemic started to spread in the UK, in early 2020, James had to leave the lab and write his PhD thesis from home. But he could not focus on the thesis alone during this uncertain time. He, along with his colleagues, began discussing how their expertise could be of use. It was through these conversations that the idea of the SARS-CoV-2 Spike protein binding to Neuropilin-1 gained traction.

“Given that my PhD research had serendipitously led me to working on this receptor, I was uniquely placed to get back into the lab and start testing the hypothesis” says James Daly.

James teamed up with a collaborative network of researchers and parked himself in the lab every day for months, while the city around him was locked down. It was a whirlwind trying to keep up with the pace of the emerging literature, learning new concepts in virology and simultaneously pushing forward with experiments.

“It was tumultuous, tiring and stressful at times but it was also the most inspiring, motivating and rewarding experience of my research career. There was a great camaraderie among the team in Bristol, and the wider international collaborative network, and I am indebted to them for their support, mentorship and friendship throughout this time” says James Daly.

Impactful research should be ambitious, exciting and collaborative.

Finally, James revealed one of the ways the SARS-CoV-2 virus recognizes and enters our cells. This raises the possibility of one day developing antiviral drugs that can inhibit this process, and has the potential to protect us against future viral infections.

Aims for impact
Now, James Daly has received funding for a five-year project, through a Wellcome Early Career Award fellowship, in Michael Malim’s lab at King’s College London. He aims to combine his experience in cell biology with the expertise of a cutting-edge infectious diseases department to continue exploring how neuropilin receptors – and the regulatory mechanisms that underpin their sorting throughout the cell – are involved in viral infections. 

“My hopes are to carry forward the lessons learned from the COVID-19 research experience – that impactful research should be ambitious, exciting and collaborative – into my future research career” says James Daly.

Read James Daly’s essay in Science to learn more.