Alvin Chew, a PhD student in the lab of Dahai Luo at Nanyang Technological University(NTU) in Singapore is an emerging structural biologist. He is now self-quarantining in Singapore. COVID-19 inserted itself into his career trajectory. (J.Jarzombek, MPI for Molecular Physiology)

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Since early January, Alvin Chew, a PhD student in the lab of Dahai Luo at (NTU) in Singapore, has been an EMBO fellow in the lab of Christos Gatsogiannis at the Max- Planck-Institute for Molecular Physiology in Dortmund, Germany. But he had to leave in a hurry and is currently self-quarantining in Singapore.

Chew’s ambitious plan was, in the first three months of 2020, to learn about cryo-electron microscopy software and take his membrane protein target through sample preparation and data collection to then have a working model in hand before returning to Singapore.

It was a tight schedule compounded by the need to adapt to a foreign culture, says Chew. When the COVID-19 outbreak began in China early this year, colleagues at the institute were calm, ‘It’s just like flu season,’ Chew recalls they told one another and ‘We are safe here.’

He had just completed sample prep and had begun collecting data from the Krios cryo-EM machine when the COVID-19 lockdown in Italy began and cases were being reported in the region in Germany where he was living and working. That left Chew less than one month for data processing of an unknown structure. And he still needed to climb a steep learning curve. “There was a growing sense of uneasiness with all the news updates,“ he says.

He kept discussing his project’s progress with his supervisor and at the same time precautions were being put in place almost daily at the institute. “Everyone in MPI had been very helpful towards each other despite the anxiety within,” he says. He felt safest at work.

Group leader Christos Gatsogiannis looks at Alvin Chew's samples. He supervises Chew's work who was trying to take his membrane protein target through sample preparation, data collection and have a working model in hand before returning to Singapore. COVID-19 interrupted that plan. 

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Two weeks into March, the number of cases in Germany had risen above 3,000 and working from home plans began to emerge. Chew hunkered down in the institute and worked through the weekend. That was mid-March. He woke up on Monday, March 16 to an urgent email from NTU asking him to return home immediately, at the latest by March 20, and to adhere to a 14-day self-quarantine upon arrival.

Chew was torn. He wanted to keep working but realized it was hailing flight cancellations. The embassy was overwhelmed with frantic calls, and he was unable to get answers to questions in order to make decisions about returning home. He needed a flight. He needed a day to pack. To clean his lab bench. To back up data. To keep discussing his project. Maybe finish his food supplies. His mind was overwhelmed with his to-do-list, he says.

What helped him the most, he says, were his colleagues who discussed options with him, helped him find a flight, pack, do all his chores and then race to the airport. “All of which happened in less than half a day,” he says. 

What matters most, he says, is personal safety. “This is a responsibility not only to myself but to the kind hosts, my home institute and the wider community,” he says. Downplaying the potential seriousness of an epidemic helped make it a pandemic and fed into considerable panic and more uncertainties lie ahead, he says.

Alvin Chew (left) and Pascal Lill, a PhD student at the Max-Planck-Institute of Molecular Physiology. "He has helped me tremendously throughout the process," says Chew. 

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Chew does not have a photo of himself at his new workplace--home--just yet. “Now I am just cooped up in my room at home and still in the process of setting up an effective work station, hence I am afraid it’s not ready for a photo.”

He is happy to see activities in structural biology related to COVID-19 going at full tilt. The work includes a paper in Science from Jason McLellan’s group at the University of Texas at Austin and colleagues at the National Institute of Allergy and Infectious Diseases: "Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation," and a Cell paperfrom a group at the University of Washington and their colleagues at Fred Hutchinson Cancer Research Center and Institut Pasteur: "Structure, Function, and Antigenicity of the SARSCoV-Spike Glycoprotein"

There is also a crystal structure on the SARS-CoV-2 main protease bound to potential drug ligand, says Chew. This is from several groups in Germany and China and published in Science. All of these are highly informative for accelerating the development of effective vaccines and drugs, he says.

Just a few of the recent structural biology papers related to COVID-19 and the virus SARS-CoV-2.

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From a new user perspective of cryo-EM data processing tools, Chew’s sense is that increasing investments to improve the user interface and design user experience for key software packages will be helpful.

And if data formats could be harmonized, it would be easier to use software across platforms, which will raise researchers’ productivity, he says.

The development and launch of accessible and reproducible methods for cryoEM grid preparation would be of great value now. “It is set to overcome another major bottleneck in cryo-EM,” he says. One example of many is for example the blot-free, pico-litre method developed by the groups of Bridget Carragher and Clint Potter at New York Structural Biology Centre. Here is a profile of Carragher and one of her papers 'Reducing effects of particle adsorption to the air–water interface in cryo-EM,' published in Nature Methods. 

Separately, Chew points out how COVID-19 brings about new types of collaborative resources. A group of scientists at universities across Europe and South America have started a COVID-19-focused initiative and website called crowdfight COVID-19 to join people, such as, for example, to connect volunteers with those who need assistance. That might be to do bioinformatic analysis on COVID-19, find a needed reagent, identify cells in micrographs or curate data.

Crowdfight.org

(Alamy Stock PhotoPhotographer / artist:Skorzewiak / Alamy Stock Photo)