Big Single-Cell Science

Art by Nikki Rosato.

It sounds like science fiction: a searchable Google Maps-like app of the 30 trillion cells of the human body. But, that’s exactly what teams of scientists around the world are working together to create. Their efforts have been made possible by new advances in single-cell biology that allows them to determine the activity of individual cells while retaining information about their location. And, once the virtual map is complete, scientists could do things like run treatment simulations to predict how a cell — and the cells near and far — might respond. That’s just one way researchers who are mapping every cell in the human body at the molecular level envision such a map being used

Single-cell biology is one of the most transformative areas of biomedical research today, Francis Collins, Ph.D., Director of the National Institutes of Health (NIH), told researchers taking part in last month’s virtual NIH-Human Cell Atlas (HCA) 2020 Joint Meeting. Collins praised participants for taking on such a huge task. “This is a good example of how Big Science…can actually empower everybody by generating new technologies, figuring out how to apply them at scale and producing publicly accessible, high-quality data sets that everybody has access to.” 

The current effort to create a map at single-cell resolution would have been unimaginable even 10 years ago, Collins says. “Over and over again — from the Human Genome Project up to right now — we’re finding out that in biomedical research these kinds of projects can move the whole enterprise forward at a really remarkable pace.” 

The rapid pace is only feasible because of careful coordination — both within and between research groups large and small that are working on the project. To that end, scientists from the single-cell community meet regularly to share results, best practices and breakthrough technologies. And, those were exactly the plans organizers from the NIH’s HuBMAP (Human BioMolecular Atlas Program) and the HCA had planned for their Joint Meeting, scheduled for March 30-April 1 in Bethesda, MD. The three-day meeting was to include 200 registered participants from about eight international consortia. 

Virtual Preparedness

The original plan for the meeting included a handful of virtual meet-ups in the fall and winter, culminating in the face-to-face workshop in Maryland. “Each of the major groups who were participating in the meeting gave a status talk, sharing challenges and particular highlights in terms of the science,” says Richard Conroy, Ph.D., Program Leader for NIH’s Office of Strategic Coordination/The Common Fund.

But, then governments imposed travel restrictions in response to the COVID-19 pandemic. What would happen without this important check-in? Organizers did not want to find out. Instead of cancelling it, organizers decided to convert the meeting into a two-day virtual event. The move allowed for an increase in participation, with just over 400 researchers attending. It also meant, Conroy says, that pre-meeting preparation was not wasted and the momentum those meetings built up was maintained.

COVID-19 Update

Because COVD-19 was on everyone’s minds, organizers decided to start the meeting with a presentation by members of the consortia that are involved in investigating the novel coronavirus. “The presentations showcased how the global scientific community can come together so quickly to work on an extremely important topic,” says Ananda Roy, Ph.D., also a Program Leader in NIH’s Office of Strategic Coordination, but not on the organizing team. 

“It also illustrates how single-cell analysis can contribute not only to generate a molecular map of the human body, but can contribute to understanding and discovering important aspects of human maladies,” Roy says. The presentations set the tone for the rest of the meeting, he adds. “They showed how different initiatives working in this space could also come together to ultimately generate the human cell atlas for normal and diseased states.” (This research was recently published and written about in Collins’ blog.)

Going Virtual

Conroy says he and his colleagues had three goals for the original in-person meeting: provide a forum for people to meet and interact, identify challenges that groups have in common and form cross-consortia teams around those challenges so that they can be most effectively addressed. 

Norbert Tavares, Ph.D. says the virtual meeting gave participants like himself a way to address major cross-consortia issues. “As long as the technical challenges persist, there will be some impetus to collaborate on solving them. These meetings help to identify potential collaborations to work on those challenges,” says Tavares who is Program Manager for Single-Cell Programs at the Chan Zuckerberg Initiative.

For example, spatial transcriptomic methods seek to characterize gene expression profiles while retaining information on the individual cells’ location in the tissue. “Key technology developers in the spatial transcriptomics space are easy to identify by just looking at the scientific literature. But, those who are struggling to implement the technologies and their specific challenges are much harder to identify. Meetings like this help to bring the two together.”

Neil Kelleher, Ph.D., is a member of HuBMAP and a Professor of Chemistry, Molecular Biosciences and Medicine at Northwestern University. He joined a cross-consortia team during the meeting that is currently drafting a white paper on raising the efficiency of antibody-based imaging, which the group plans to submit for publication. (Antibody-based imaging repurposes therapeutics to deliver imaging agents to get better pictures of cancer cells, for example.)

“Coordination within a consortium is challenging and among consortia is even harder,” Kelleher says. But, meeting virtually is an efficient and worthwhile way for these groups to work together, he adds.

Future of Virtual

Organizers and participants agree that the meeting’s goals were met: researchers interacted, challenges were identified and teams were formed. Still, Conroy says, fewer connections were probably made because the meeting was shorter and participants didn’t have as many opportunities for socializing as they would have had in person. “But on the other hand, many more people engaged in the process, particularly people who wouldn’t have been able to travel in person to the meeting. Likewise, I think doing it online also provides a more natural segue for follow-up.”

In-person meetings will return when possible if for no other reason than some of the best conversations about science happens in hallways and over coffee or dinner at fact-to-face meetings. But, the genie is out of the bottle. Virtual meetings are also here to stay now that those who were wary or fearful of the technology have had to adapt to it. At the very least, hybrid events in which virtual preparation is done in advance and online meetings of small groups happen afterwards will give researchers the chance to be more collaborative and more productive. And that’s what science needs if investigators are going to realize their futuristic visions for the benefit of us all.