The Google-owned company developed a system that can reliably predict the 3D shapes of proteins.
- Scientists have long been puzzled by how specific chains of amino acids go on to form three-dimensional proteins.
- DeepMind developed a system that's able to predict "protein folding" in a fraction of the time of human experiments, and with unprecedented accuracy.
- The achievement could greatly improve drug research and development, as well as bioengineering pursuits.
DeepMind<p>In the biennial competition, teams analyze about 100 proteins with the goal of predicting their eventual 3D shape. A protein's shape determines its function. For example, a protein can become an antibody that binds to foreign particles to protect, an enzyme that carries out chemical reactions, or a structural component that supports cells.</p><p>Proteins start as a string of hundreds of amino acids. Within a protein, pairs of amino acids can interact in numerous ways, and these particular interactions determine the final shape of the protein. But given the sheer number of possible interactions, it's incredibly difficult to predict a protein's physical shape. Difficult, but not impossible.</p><p>Since CASP began, scientists have been able to predict the shape of some simple proteins with reasonable accuracy. CASP is able to verify the accuracy of these predictions by comparing them to the actual shape of proteins, which it obtains through the unpublished results of lab experiments.</p><p>But these experiments are difficult, often taking months or years of hard work. The shapes of some proteins have eluded scientists for decades. As such, it's hard to overstate the value of having an AI that's able to churn out this work in just hours, or even minutes.</p><p>In 2018, DeepMind, which was acquired by Google in 2014, startled the scientific community when its AlphaFold algorithm won the CASP13 contest. AlphaFold was able to predict protein shapes by "training" itself on vast amounts of data on known amino acid strings and their corresponding protein shapes.</p><p>In other words, AlphaFold learned that particular amino acid configurations — say, distances between pairs, angles between chemical bonds — signalled that the protein would likely take a particular shape. AlphaFold then used these insights to predict the shapes of unmapped proteins. AlphaFold's performance in the 2018 contest was impressive, but not reliable enough to consider the problem of "protein folding" solved.</p>
DeepMind<p>In the latest contest, DeepMind used an updated version of AlphaFold. It combines the previous deep-learning strategy with a new "attention algorithm" that accounts for physical and geometric factors. Here's how <a href="https://deepmind.com/blog/article/alphafold-a-solution-to-a-50-year-old-grand-challenge-in-biology" target="_blank">DeepMind describes it:</a></p><p style="margin-left: 20px;">"A folded protein can be thought of as a "spatial graph", where residues are the nodes and edges connect the residues in close proximity. This graph is important for understanding the physical interactions within proteins, as well as their evolutionary history."</p><p style="margin-left: 20px;">"For the latest version of AlphaFold, used at CASP14, we created an attention-based neural network system, trained end-to-end, that attempts to interpret the structure of this graph, while reasoning over the implicit graph that it's building. It uses evolutionarily related sequences, multiple sequence alignment (MSA), and a representation of amino acid residue pairs to refine this graph."</p><p>CASP measures prediction accuracy through the "Global Distance Test (GDT)", which ranges from 0-100. The new version of AlphaFold scored a median of 92.4 GDT for all targets.</p>
An overfished planet needs a better solution. Fortunately, it's coming.
- Cell-based fish companies are getting funding and making progress in offering a new wave of seafood.
- Overfishing and rising ocean temperatures are destroying entire ecosystems.
- The reality of cell-based fish is likely five to 10 years away.
Future of Food: This genetically engineered salmon may hit U.S. markets as early as 2020<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="466fe20063a2292a48789f370c04ea13"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/bco7rPyKwec?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>While cell-based beef is getting all the press, companies like BlueNalu recently raised $24.5 million in funding. The San Diego-based start-up <a href="https://www.sandiegouniontribune.com/business/story/2019-12-25/lab-grown-fish-just-got-real-san-diego-startup-shows-off-first-slaughter-free-yellowtail#:~:text=A%20San%20Diego%20foodtech%20startup,many%20researchers%20only%20dream%20of" target="_blank">extracts</a> muscle cells from an anesthetized fish, treats the cells with enzymes in a culture, places the mixture in a nutrient solution in a bioreactor, spins it all around in a centrifuge, and finally 3D-prints the new concoction into the desired shape.</p><p>The goal isn't to perfectly replicate a fish that you'd find on ice in your local market. No brain, skin, organs, or even possibility of consciousness are in this creature. In a strange twist, this makes cell-based seafood a potential food source for vegetarians and vegans, since the Adam fish can be returned to the waters unharmed. </p><p>One current solution to overfishing—fish farms—comes with it a host of problems, including the proliferation of sea lice, which have a tendency to escape the porous boundaries to infect wild fish. Bonus: with cell-based fish, you won't run into any issues with mercury or <a href="https://bigthink.com/surprising-science/microplastics-soil" target="_self">microplastics</a>. </p><p>What you'll (hopefully) purchase is a good-tasting product, which has thus far been elusive. BlueNalu CEO, <a href="https://apnews.com/5327a2c3a8e74adab0cc63d5994ffc72" target="_blank">Lou Cooperhouse</a>, is confident his company's product will eventually meet standards set by your taste buds. </p><p style="margin-left: 20px;">"Our medallions of yellowtail can be cooked via direct heat, steamed or even fried in oil; can be marinated in an acidified solution for applications like poke, ceviche, and kimchi, or can be prepared in the raw state."</p>
Photo: aleksandr / Shutterstock<p>There are barriers, of course. As with pluripotent meats, cell-based fish are expensive. A spicy salmon roll produced by the start-up, Wildtype, <a href="https://singularityhub.com/2020/09/16/this-startup-is-growing-sushi-grade-salmon-from-cells-in-a-lab/" target="_blank">cost $200</a> to make. It's going to take a while for the price to drop and consumer demand to rise; estimates are five to ten years.</p><p>Another issue is indicative of solar power and wind energy trying to cut in on Big Oil: the seafood industry doesn't want to lose its profit margin. Of course, like oil companies, Big Seafood is betting on a finite resource. The sooner they realize that, the better. </p><p>Then there's production, which is where education comes into play. Former BlueNalu Chairman Chris Somogyi tries to <a href="https://www.npr.org/sections/thesalt/2019/05/05/720041152/seafood-without-the-sea-will-lab-grown-fish-hook-consumers" target="_blank">demystify</a> the laboratory process. </p><p style="margin-left: 20px;">"We aren't using CRISPR technology. We aren't introducing new molecules into the diet. We're not introducing a new entity that doesn't exist in nature. The approval will be about whether this is safe, clean and are the manufacturing processes reliable and accountable."</p><p>If there's an ick factor to cell-based fish, remember that most processed foods are already created in laboratories. There are no Oreo trees or ketchup plants to harvest. </p><p>For now, these start-ups and others like them will have to figure out how to create non-energy-intensive and cost-prohibitive solutions for spinning up seafood inside of a petri dish. Novelty alone will create enough demand to get them going, as <a href="https://www.cnbc.com/2020/08/04/beyond-meat-bynd-q2-2020-earnings.html#:~:text=Net%20sales%20rose%2069%25%20to,since%20many%20are%20temporarily%20shuttered." target="_blank" rel="noopener noreferrer">precedent</a> in the lab-grown meat industry shows. </p><p>The reality is that we need to go down this path. There are too many humans and not enough resources. While we can hope (as David Attenborough does in his <a href="https://www.netflix.com/title/80216393" target="_blank" rel="noopener noreferrer">new Netflix documentary</a>) that national governments will create more no-fish zones, there's no guarantee that will happen. We need science to win this one. </p><p>--</p><p><em>Stay in touch with Derek on <a href="http://www.twitter.com/derekberes" target="_blank" rel="noopener noreferrer">Twitter</a> and <a href="https://www.facebook.com/DerekBeresdotcom" target="_blank" rel="noopener noreferrer">Facebook</a>. His new book is</em> "<em><a href="https://www.amazon.com/gp/product/B08KRVMP2M?pf_rd_r=MDJW43337675SZ0X00FH&pf_rd_p=edaba0ee-c2fe-4124-9f5d-b31d6b1bfbee" target="_blank" rel="noopener noreferrer">Hero's Dose: The Case For Psychedelics in Ritual and Therapy</a>."</em></p>
Techshot's 3D BioFabrication Facility successfully printed human heart tissue aboard the International Space Station.
All that's fit to bioprint<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDQ0MTc4OS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY0NjUyMTkxN30.c02tUlYJLxdekTGR5ExOagL2Sh-5rmWN6pYkqger920/img.jpg?width=1245&coordinates=0%2C210%2C0%2C210&height=700" id="549d0" class="rm-shortcode" data-rm-shortcode-id="681571f2317ce5f65b105b6fb5aabd51" data-rm-shortcode-name="rebelmouse-image" alt="Dr. Eugene Boland" />
Dr. Eugene Boland, Techshot's chief scientist, presents the 3D BioFabrication Facility at NASA's Kennedy Space Center, Florida
A heart from your new BFF<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="1fa24e6ada521bcdac46de275c37f2da"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/p_hauPqouH8?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>In partnership with <a href="https://www.nscrypt.com/about-us/" target="_blank">nScrypt</a>, Techshot developed the BFF to manufacture human tissue in space. In July 2019, they launched the bioprinter aboard the SpaceX CRS-18 cargo mission to be delivered to the International Space Station. There, it was loaded up with nerve, muscle, and vascular bioinks. As the BFF pinned the cells together in a culturing cassette, generating layers several times thinner than a human hair, the microgravity environment ensured the low-viscosity structure kept together. That's courtesy of the same surface tension property that allows for those <a href="https://www.youtube.com/watch?v=H_qPWZbxFl8" target="_blank">moving water spheres astronauts love to play with</a>.</p><p>"So, now you can have a vascular cell where you want a blood vessel to be, the nerve cell where you want the nerve to pass through, and muscle cells where you need a muscle bundle to be," Boland said. "All of those will stay where you put them in three-dimensions and then grow and mature where you want them."</p><p>A non-cellular ink was added to the mix to provide a bit of framework and prevent cells from sliding around during the printing process. But because Earth's gravity had less pull, this framework didn't need to be as ridged as terrestrial scaffolding. This non-cellular ink was water-soluble, meaning it could be washed away after the printing was complete. The end result, a more natural fabrication of human tissue.</p><p>Once 25 percent of the cells needed for the mature tissue were in place, the cell-culturing cassette was moved to another payload, the Advanced Space Experiment Processor (ADSEP). There, the cells lived and grew as they would naturally. Fully differentiated cells signaled to the adult stems cells that they should be heart cells. The stem cells grew and multiplied, supported by the nutrients provided in the ink. A few weeks later and the cassette was home to human heart tissue.</p><p>This January, <a href="https://www.prnewswire.com/news-releases/success-3d-bioprinter-in-space-prints-with-human-heart-cells-300982759.html" target="_blank">Techshot announced</a> the BFF had cultured successful test prints aboard the ISS. These heart prints measured 30 mm long by 20 mm wide by 12.6mm high. In a follow-up experiment, the BFF also manufactured <a href="https://techshot.com/techshot-successfully-completes-knee-cartilage-test-prints-in-space/" target="_blank" rel="noopener noreferrer">test prints of a partial human knee meniscus</a>, the soft cartilage that acts as a shock absorber between your shinbone and thighbone.</p>
The future of medicine is in space?<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDQ0MTc5MS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY2MjQwODUxOH0.VAg1FIZkGz_IOCaGUAHxylX1h44qA2-tk-9odXPoLT0/img.jpg?width=1245&coordinates=0%2C118%2C0%2C118&height=700" id="18054" class="rm-shortcode" data-rm-shortcode-id="932d3caca0897797883d941a6255885e" data-rm-shortcode-name="rebelmouse-image" />
NASA Astronaut Jessica Meir prepares Techshot's cell-culturing cassettes for their return trip to Earth.
Credit: NASA Johnson/Flickr<p>For its next run, Techshot wants to improve the cell-culturing cassette, refining conditions and more effectively flushing out trapped air. Its researchers are also looking into making cells in orbit. Then there is the process of scaling up from test prints to functioning tissue pieces (say, heart patches) to fully operational organs. Then there are the challenges of space flight and <a href="https://bigthink.com/surprising-science/3d-printing-body-parts" target="_self">the long road of regulation</a>.</p><p>"We're dedicated to the long haul here," Boling said during our interview. "We have agreements with NASA that permit us to iterate and fly-and-try to continue and improve. We brought the BFF and ADSEP back from the space station late summer to make those improvements based on what we have learned so we can send it back up."</p><p>Yet, the windfall goes well beyond shoring up our stock of donor organs. Bioprinting has the potential to dramatically advance the field of personalized medicine. For example, one danger of transplants is rejection by the host body. This happens when a recipient's immune system views the life-saving tissue as a foreign invader and attacks it. <a href="https://med.stanford.edu/news/all-news/2010/09/researchers-find-faster-less-intrusive-way-to-identify-transplant-recipients-organ-rejection.html#:~:text=If%20organ%20function%20drops%2C%20doctors,the%20first%20year%20after%20transplant." target="_blank">About 40 percent of heart recipients</a> experience acute rejection in the first year, requiring doctors to prescribe immunosuppressant drugs.</p><p>Crafting an organ from a patient's personal stem-cell stock has the potential to reduce this risk. Replacement parts, such as heart patches, could also be patient-specific. Test prints could be constructed to analyze how a patient's system responds to specific drugs and treatments, taking <em>in vitro</em> experiments out of the Petri dish and into a microenvironment more representative of the natural human body.</p><p>"Instead of the trial-and-error medicine of the 20th century, you'll have the personalized medicine that has always been just around the corner. [This technology] may be an answer to that," Boland said.</p><p>And we could take bioprinting farther into space. Boling foresees a future where the technology could <a href="https://www.nasa.gov/artemisprogram" target="_blank" rel="noopener noreferrer">travel with us to the Moon</a> or beyond. There it could serve personalized pharmaceutical needs for stationed astronauts, or if paired with a Cell Factory, it could print meats made from bovine or pig cells. Ethical, yet potentially indistinguishable from its farm-raised counterpart.</p><p>We've come a long way since the 1950s. Many people are alive today thanks to what that first kidney transplant showed medical science. True, Techshot's test prints are small compared to an entire human organ, with its complex and interconnected network of epithelial, connective, muscle, and nervous tissue. But if printing an organ is equivalent to urban planning a cellular city, then Techshot's accomplishment is certainly the first of many skyscrapers toward that goal. That goal could be the proof on concept that saves many more.</p>
A recent study tested how well the fungi species Cladosporium sphaerospermum blocked cosmic radiation aboard the International Space Station.
- Radiation is one of the biggest threats to astronauts' safety during long-term missions.
- C. sphaerospermum is known to thrive in high-radiation environments through a process called radiosynthesis.
- The results of the study suggest that a thin layer of the fungus could serve as an effective shield against cosmic radiation for astronauts.
Shunk et al.<p>Additionally, the fungus is self-replicating, meaning astronauts would potentially be able to "grow" new radiation shielding on deep-space missions, instead of having to rely on a costly and complicated interplanetary supply chain.</p><p>Still, the researchers weren't sure whether <em>C. sphaerospermum</em> would survive on the space station. Nils J.H. Averesch, a co-author of the <a href="https://www.biorxiv.org/content/10.1101/2020.07.16.205534v1.full.pdf" target="_blank">study published on the preprint server bioRxiv</a>, told <a href="https://www.syfy.com/syfywire/fungus-that-eats-radiation-could-be-cosmic-ray-shield" target="_blank">SYFY WIRE</a>:</p><p style="margin-left: 20px;">"While on Earth, most sources of radiation are gamma- and/or X-rays; radiation in space and on Mars (also known as GCR or galactic cosmic radiation) is of a completely different kind and involves highly energetic particles, mostly protons. This radiation is even more destructive than X- and gamma-rays, so not even survival of the fungus on the ISS was a given."</p>
International Space Station
NASA<p>To be sure, the researchers said more research is needed, and that <em>C. sphaerospermum</em> would likely be used in combination with other radiation-shielding technology aboard spacecraft. But the findings highlight how relatively simple biotechnologies may offer outsized benefits on upcoming space missions.</p><p style="margin-left: 20px;">"Often nature has already developed blindly obvious yet surprisingly effective solutions to engineering and design problems faced as humankind evolves – C. sphaerospermum and melanin could thus prove to be invaluable in providing adequate protection of explorers on future missions to the Moon, Mars and beyond," the researchers wrote.</p>
Scientists figured out how a certain treatment for skin cancer gives some patients a visual "superpower."
- In the early 2000s, it was reported that some cancer patients being treated with chlorin e6 were experiencing enhanced night vision.
- Using a molecular simulation, researchers discovered that a chlorin e6 injection under infrared light activates vision by changing retinal in the same way that visible light does.
- Researchers hope that this chemical reaction could one day be harnessed to help treat certain types of blindness and sensitivity to light.
In the early 2000s, it was reported that a certain kind of skin cancer treatment called photodynamic therapy, which uses light to destroy malignant cells, had a bizarre side effect: It was giving patients enhanced night time vision.An essential component to this therapy is a photosensitive compound called chlorin e6. Some people being treated with chlorin e6 were upset to discover that they were seeing silhouettes and outlines in the dark. Researchers think they might finally know why this happens.
The chemistry of vision
Rods and cones photoreceptors in a human retina.
Photo Credit: Dr. Robert Fariss, National Eye Institute, NIH / Flickr
"Seeing" happens when a series of receptors in the retina, the cones and rods, collect light. Rods contain a lot of rhodopsin, a photosensitive protein that absorbs visible light thanks to an active compound found in it called retinal. When retinal is exposed to visible light, it splits from rhodopsin. This then allows the light signal to be converted into an electrical signal that the visual cortex of our brains interprets into sight. Of course, there is "less light" at night, which actually means that light radiation is not in a domain visible to humans. It's at higher wavelengths (the infrared level) that retinal is not sensitive to. Hence, why we can't see in the dark like many critters can.
But the vision process can be activated by another interaction of light and chemistry. As it turns out, a chlorin e6 injection under infrared light changes retinal in the same way that visible light does. This is the cause of the unforeseen night vision side effect of the treatment."This explains the increase in night-time visual acuity," chemist Antonio Monari, from the University of Lorraine in France, told CNRS. "However, we did not know precisely how rhodopsin and its active retinal group interacted with chlorin. It is this mechanism that we have now succeeded in elucidating via molecular simulation."
"Molecular simulation" is a method that uses an algorithm that integrates the laws of quantum and Newtonian physics to model the functioning of a biological system over time. The team used this method to mimic the biomechanical movements of individual atoms – that is, their attraction or repulsion to one another – along with the making or breaking of chemical bonds.
"For our simulation we placed a virtual rhodopsin protein inserted in its lipid membrane in contact with several chlorin e6 molecules and water, or several tens of thousands of atoms," Monari explained to CNRS. "Our super-calculators ran for several months and completed millions of calculations before they were able to simulate the entire biochemical reaction triggered by infrared radiation." In nature, this phenomena occurs within fractions of a nanosecond.
The molecular simulation showed that when the chlorin e6 molecule absorbs the infrared radiation, it interacts with the oxygen present in the eye tissue and transforms it into reactive, or singlet, oxygen. In addition to killing cancer cells, "singlet oxygen" can also react with retinal to enable a slightly enhanced eyesight at night, when light waves are at the infrared level.
Now that researchers know why the "supernatural" side effect occurs, they may be able to limit the chance of it happening to patients undergoing photodynamic treatment. Thinking further out, the researchers hope for the possibility that this chemical reaction could be harnessed to help treat certain types of blindness and sensitivity to light.
Ultimately, researchers say that this has been a big flex for the power of molecular simulations, which can give us astonishing scientific insights like this.
"Molecular simulation is already being used to shed light on fundamental mechanisms – for example, why certain DNA lesions are better repaired than others – and enable the selection of potential therapeutic molecules by mimicking their interaction with a chosen target," Monari told CNRS.Don't hold your breath on night vision eyedrops though.