Where citizen science meets the coronavirus—and how you can help

Creators of the popular protein-folding game, Foldit, are seeking help to design a treatment for COVID-19.

Coronavirus around blood cells.

Photo: Getty Images
  • Since being founded in 2008, the crowdsourced protein-folding game, Foldit, has helped solve many novel problems.
  • In recent months, the Foldit team has presented its community with problems relating to COVID-19.
  • Foldit founder, David Baker, says over 20,000 different designs for potential COVID-19 antiviral proteins have been submitted.

In 2008, University of Washington professor David Baker created the Foldit research project. As a protein research scientist he had spent a good portion of his career designing methods to predict three-dimensional structures associated with proteins. His group initially developed an algorithm for protein structure prediction called Rosetta, which they then turned into a distributed computing project.

The initial incarnation, Rosetta@home, allowed citizen scientists to help out, much as astronomy enthusiasts have crowdsourced research and discovered new planets. Foldit is the evolution of Rosetta@home. Upon the project's launch it boasted 240,000 registered users. By gamifying protein folding, Baker's team helped the field of citizen science blossom.

There have been many rewards. Since its launch, Baker's team has posed over 2,000 design puzzles to their community. Foldit players helped to solve a 15-year problem relating to a monkey virus in 2011. The following year, gamers successfully redesigned a protein initially created by Baker's team. Now this community is being asked to help out with another daunting task: solving the coronavirus problem.

Foldit Lab Report 7: Quarantine Edition

While most Americans are self-isolating, which certainly helps stop the spread of COVID-19, Baker is asking Foldit gamers to help hunt for proteins that could stop the virus in its tracks. They're specifically seeking proteins that block the viruses's entry into new cells upon entering the human body. If successful, new antiviral drugs could be developed that would reduce the symptoms once you're infected.

Brian Koepnick, who works in Baker's lab and helps run Foldit, says the diversity of responses they receive to problems posed is a necessary step in discovering new solutions.

"We find that the creativity of crowdsourcing is really, really useful—if you ask 100 people to do something, they'll do it in 100 different ways. That's really valuable for us in protein design problems."

As COVID-19 plagues the entire planet, driving fear and uncertainty in citizens, at least there is precedent for this disease. We know that this type of virus infects cells through its spike protein, which latches onto certain cells and proliferate. Baker says that a protein that "grabs the coronavirus's spike protein might be able to run interference," preventing it from attaching to other cells and spreading.

Every puzzle Baker's lab publishes is online for roughly a week. They work with up-to-the-minute information about COVID-19; thus, the team is constantly updating its puzzles. According to Baker, a few entries seem promising—there have been 20,000 different designs submitted already—though as with any treatment, each design will require real-world testing.

Baker notes that they've successfully crowdsourced strategies for dealing with flu, which brings hope that a treatment could be found in this situation. "In general, the coronaviruses appear to mutate less than influenza viruses. So that makes them a little bit easier of a target."

Foldit players have come up with more than 20,000 different designs for potential COVID-19 antiviral proteins. Scientists plan to test 99 of the most promising designs (shown here) in the lab.

Photo: Foldit

This is truly an unprecedented moment in history. While researchers have worked on pandemics across the planet before, there has never been such a sense of urgency. Our global response to this coronavirus is likely to set the stage for how we treat diseases of this magnitude in the future. And as science writer Ed Yong says, there is reason for hope.

"The first steps so far have actually been encouragingly quick. A vaccine candidate has already entered early safety trials after a record breakingly short time from actually identifying and sequencing the genome of this new virus."

There is a long road from trials to implementation, Yong says. We're 12 to 18 months away from a vaccine. Still, the rapidity of this process has been aided by the sheer number of researchers simultaneously working on the problem.

Give the number of players on Foldit's platform, it's not about expertise as much as, in Baker's words, persistence and ingenuity. Citizen science is one of the greatest benefits of the digital age. In many ways, platforms like Foldit are leading the way to a new form of education. If you're interested in contributing, download the software and start playing.

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Stay in touch with Derek on Twitter and Facebook. His next book is "Hero's Dose: The Case For Psychedelics in Ritual and Therapy."

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The surprise reason sleep-deprivation kills lies in the gut

New research establishes an unexpected connection.

Reactive oxygen species (ROS) accumulate in the gut of sleep-deprived fruit flies, one (left), seven (center) and ten (right) days without sleep.

Image source: Vaccaro et al, 2020/Harvard Medical School
Surprising Science
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  • Surprisingly, the direct cause seems to be a buildup of Reactive Oxygen Species in the gut produced by sleeplessness.
  • When the buildup is neutralized, a normal lifespan is restored.

We don't have to tell you what it feels like when you don't get enough sleep. A night or two of that can be miserable; long-term sleeplessness is out-and-out debilitating. Though we know from personal experience that we need sleep — our cognitive, metabolic, cardiovascular, and immune functioning depend on it — a lack of it does more than just make you feel like you want to die. It can actually kill you, according to study of rats published in 1989. But why?

A new study answers that question, and in an unexpected way. It appears that the sleeplessness/death connection has nothing to do with the brain or nervous system as many have assumed — it happens in your gut. Equally amazing, the study's authors were able to reverse the ill effects with antioxidants.

The study, from researchers at Harvard Medical School (HMS), is published in the journal Cell.

An unexpected culprit

The new research examines the mechanisms at play in sleep-deprived fruit flies and in mice — long-term sleep-deprivation experiments with humans are considered ethically iffy.

What the scientists found is that death from sleep deprivation is always preceded by a buildup of Reactive Oxygen Species (ROS) in the gut. These are not, as their name implies, living organisms. ROS are reactive molecules that are part of the immune system's response to invading microbes, and recent research suggests they're paradoxically key players in normal cell signal transduction and cell cycling as well. However, having an excess of ROS leads to oxidative stress, which is linked to "macromolecular damage and is implicated in various disease states such as atherosclerosis, diabetes, cancer, neurodegeneration, and aging." To prevent this, cellular defenses typically maintain a balance between ROS production and removal.

"We took an unbiased approach and searched throughout the body for indicators of damage from sleep deprivation," says senior study author Dragana Rogulja, admitting, "We were surprised to find it was the gut that plays a key role in causing death." The accumulation occurred in both sleep-deprived fruit flies and mice.

"Even more surprising," Rogulja recalls, "we found that premature death could be prevented. Each morning, we would all gather around to look at the flies, with disbelief to be honest. What we saw is that every time we could neutralize ROS in the gut, we could rescue the flies." Fruit flies given any of 11 antioxidant compounds — including melatonin, lipoic acid and NAD — that neutralize ROS buildups remained active and lived a normal length of time in spite of sleep deprivation. (The researchers note that these antioxidants did not extend the lifespans of non-sleep deprived control subjects.)

fly with thought bubble that says "What? I'm awake!"

Image source: Tomasz Klejdysz/Shutterstock/Big Think

The experiments

The study's tests were managed by co-first authors Alexandra Vaccaro and Yosef Kaplan Dor, both research fellows at HMS.

You may wonder how you compel a fruit fly to sleep, or for that matter, how you keep one awake. The researchers ascertained that fruit flies doze off in response to being shaken, and thus were the control subjects induced to snooze in their individual, warmed tubes. Each subject occupied its own 29 °C (84F) tube.

For their sleepless cohort, fruit flies were genetically manipulated to express a heat-sensitive protein in specific neurons. These neurons are known to suppress sleep, and did so — the fruit flies' activity levels, or lack thereof, were tracked using infrared beams.

Starting at Day 10 of sleep deprivation, fruit flies began dying, with all of them dead by Day 20. Control flies lived up to 40 days.

The scientists sought out markers that would indicate cell damage in their sleepless subjects. They saw no difference in brain tissue and elsewhere between the well-rested and sleep-deprived fruit flies, with the exception of one fruit fly.

However, in the guts of sleep-deprived fruit flies was a massive accumulation of ROS, which peaked around Day 10. Says Vaccaro, "We found that sleep-deprived flies were dying at the same pace, every time, and when we looked at markers of cell damage and death, the one tissue that really stood out was the gut." She adds, "I remember when we did the first experiment, you could immediately tell under the microscope that there was a striking difference. That almost never happens in lab research."

The experiments were repeated with mice who were gently kept awake for five days. Again, ROS built up over time in their small and large intestines but nowhere else.

As noted above, the administering of antioxidants alleviated the effect of the ROS buildup. In addition, flies that were modified to overproduce gut antioxidant enzymes were found to be immune to the damaging effects of sleep deprivation.

The research leaves some important questions unanswered. Says Kaplan Dor, "We still don't know why sleep loss causes ROS accumulation in the gut, and why this is lethal." He hypothesizes, "Sleep deprivation could directly affect the gut, but the trigger may also originate in the brain. Similarly, death could be due to damage in the gut or because high levels of ROS have systemic effects, or some combination of these."

The HMS researchers are now investigating the chemical pathways by which sleep-deprivation triggers the ROS buildup, and the means by which the ROS wreak cell havoc.

"We need to understand the biology of how sleep deprivation damages the body so that we can find ways to prevent this harm," says Rogulja.

Referring to the value of this study to humans, she notes,"So many of us are chronically sleep deprived. Even if we know staying up late every night is bad, we still do it. We believe we've identified a central issue that, when eliminated, allows for survival without sleep, at least in fruit flies."

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