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{"version":"1.1","identifier":"post-106746","language":"en","title":"Scientists Hacked a Cell's DNA and Made a Biocomputer Out of It","documentStyle":{"backgroundColor":"#fafafa"},"layout":{"columns":7,"width":1024,"margin":100,"gutter":20},"components":[{"role":"header","layout":"headerPhotoLayout","components":[{"role":"photo","layout":"headerPhotoLayout","URL":"bundle:\/\/scientists-hacked-cells-dna-made-it-a-biocomputer-1.jpg"}],"behavior":{"type":"parallax","factor":0.8}},{"role":"container","layout":{"columnSpan":7,"columnStart":0,"ignoreDocumentMargin":true},"style":{"backgroundColor":"#fafafa"},"components":[{"role":"title","text":"Scientists Hacked a Cell's DNA and Made a Biocomputer Out of It","textStyle":"default-title","layout":"title-layout"},{"role":"byline","text":"by Shelly Fan | Apr 12, 2017 | 8:00 AM","textStyle":"default-byline","layout":"byline-layout"},{"role":"body","text":"Our brains are often compared to computers, but in truth, the billions of cells in our bodies may be a better analogy. The squishy sacks of goop may seem a far cry from rigid chips and bundled wires, but cells are experts at taking inputs, running them through a complicated series of logic gates and producing the desired programmed output.","format":"markdown","textStyle":"dropcapBodyStyle","layout":"body-layout"},{"role":"body","text":"Take beta cells in the pancreas, which manufacture and store insulin. If they detect a large spike in blood sugar, then they release insulin; else they don\u2019t. Each cell adheres to commands like these, allowing us\u2014the organism\u2014to operate normally.","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"body","text":"This circuit-like nature of cellular operations is not just a handy metaphor. About 50 years ago, scientists began wondering: what if we could hijack the machinery behind these algorithms and reprogram the cells to do whatever we want?","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"body","text":"Now, a team of scientists led by [Dr. Wilson Wong](http:\/\/wilsonwonglab.org\/) at Boston University directly hacked a human cell\u2019s operating guide\u2014its genetic code\u2014and enhanced it with synthetic biocircuits that allowed it to obey over 100 sets of different logical operations, effectively uprooting nature as the sole programmer of life.","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"body","text":"Although these cells don\u2019t have any immediate use, the tools developed will likely benefit other bioengineers eager to tinker with evolution. And the promises of synthetic biology are great.","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"body","text":"\u201cThese re-engineered organisms will change our lives over the coming years, leading to cheaper drugs, 'green' means to fuel our cars and targeted therapies for attacking 'superbugs' and diseases, such as cancer,\u201d [wrote](http:\/\/www.nature.com\/nrg\/journal\/v11\/n5\/full\/nrg2775.html) Drs. Ahmad Khalil and James Collins at Boston University, who were not involved in the study.","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"heading3","text":"Hacking life","format":"markdown","textStyle":"default-heading-3","layout":"heading-layout"},{"role":"body","text":"The work, [published](http:\/\/www.nature.com\/nbt\/journal\/vaop\/ncurrent\/full\/nbt.3805.html) in the prestigious journal _Nature Biotechnology_, builds on decades of previous research that aims to turn our cells into tiny, powerful microcomputers.","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"body","text":"\u201cA lot of synthetic biology is motivated by this idea that\u2026you only understand something if you can build it,\u201d [says](https:\/\/www.washingtonpost.com\/news\/speaking-of-science\/wp\/2017\/03\/09\/scientists-create-designer-yeast-in-major-step-toward-synthetic-life\/?utm_term=.49b7e3d43257) Dr. Joel Bader, a computational biologist at Johns Hopkins University who was not involved in the study.","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"body","text":"Because of their relatively simple circuitry, most work has focused on bacteria and baker\u2019s yeast. A few years ago, scientists [tinkered with](http:\/\/www.nature.com\/nrmicro\/journal\/v12\/n5\/abs\/nrmicro3240.html) the yeast\u2019s metabolic pathways and engineered it to produce a molecule used to make anti-malaria drugs from sugar. Other teams have [made bacteria](https:\/\/www.technologyreview.com\/s\/601641\/a-big-leap-for-an-artificial-leaf\/) that convert carbon dioxide into liquid fuels, essentially paving the way for artificial photosynthesis. Scientists have even managed to [link together](http:\/\/www.the-scientist.com\/?articles.view\/articleNo\/46170\/title\/Synthetic-Biology-Comes-into-Its-Own\/) two synthetic gene circuits, allowing teams of bacteria to carry out simple computations.","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"body","text":"But extending these successes to mammalian cells has been extremely challenging. At its core, synthetic biology uses molecular tools that snip, fuse, block or otherwise manipulate an organism\u2019s DNA. Unfortunately, the ones used to tinker with a bacteria or yeast\u2019s genome is useless in mammalian cells.","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"body","text":"What\u2019s more, targeting one gene isn\u2019t enough. To program new genetic biocircuits, scientists often need to regulate the activity of a dozen genes: amping some up while shutting others down. For things to operate as planned, each component of the system has to work effectively and in sync.","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"body","text":"Scientists have traditionally tried to do this with a family of proteins called transcription factors, which bind to DNA and regulate its expression\u2014that is, whether or not it gets recoded into proteins. But all of these factors behave a bit differently, making it tough to use multiple factors at once.","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"body","text":"Because of this, \u201ccircuits with multiple inputs and multiple outputs remain scarce,\u201d [explains](http:\/\/www.nature.com\/nbt\/journal\/vaop\/ncurrent\/full\/nbt.3805.html) Wong.","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"heading3","text":"Biological Boolean","format":"markdown","textStyle":"default-heading-3","layout":"heading-layout"},{"role":"body","text":"To get around these problems, Wong\u2019s team turned to a powerful molecular multi-tool: DNA recombinases, which bind to specific sequences on a DNA strand, make a cut and stitch up any open ends (\u201crecombine\u201d DNA pieces).","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"body","text":"It\u2019s like editing a video on film: to delete or add scenes, the filmmaker needs to precisely cut the physical film, toss or insert additional bits and tape everything back together.","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"body","text":"In this way, scientists can control whether or not a protein is produced: when the DNA recombinase becomes active, it chops away a gene\u2014and voila, no protein; otherwise, the cell makes the protein as usual. It\u2019s the biological equivalent of a binary system, performing the simplest of logical operations\u2014a NOT gate (if something happens, don\u2019t do something).","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"body","text":"If you\u2019ve ever played around with an Arduino, you\u2019d probably agree the simplest way to build a circuit is to have a light bulb as output. Synthetic biology, for all its complexity, is the same.","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"body","text":"The \u201clight bulb\u201d that the team used is actually a gene snippet that encodes a protein that glows green under UV light, called green fluorescent protein, or GFP. Normally a cell would happily make the protein and itself glow. To build their NOT gate, the team added another gene instruction before the GFP gene\u2014a termination sequence, which is the genetic version of \u201cstop right there!\u201d","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"body","text":"To make their circuit more complex, the team added an if-then command. Here\u2019s how it worked: they made a DNA recombinase that can snip away the termination sequence, but only when it\u2019s in the presence of a drug.","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"body","text":"When the cell doesn\u2019t sense the drug, the DNA recombinase is inactive, the termination sequence stays in place and the cell remains translucent and colorless. If a drug is added, then the recombinase jumps into action and cuts away the NOT gate. Output? The cellular \u201clight bulb\u201d comes on.","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"body","text":"While a glowing cell may seem trivial, scientists can engineer cells to light up when it detects biomarkers for cancer, HIV or other diseases. As Wong [explains](https:\/\/www.wired.com\/2017\/03\/biologists-made-logic-gates-dna\/), you can mix a patient\u2019s blood sample with engineered cells and instantly get your readout\u2014a much cheaper and faster alternative to current diagnostics that require expensive machines.","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"body","text":"Not content with simple circuits, the team went on to construct [113 circuits](http:\/\/www.nature.com\/nbt\/journal\/vaop\/ncurrent\/full\/nbt.3805.html) in human kidney and immune cells. A staggering [96.5 percent](http:\/\/www.nature.com\/nbt\/journal\/vaop\/ncurrent\/full\/nbt.3805.html) of them worked as intended without needing further optimization, which is quite impressive because biological tools can be extremely finicky.","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"body","text":"\u201cIn my personal experience building genetic circuits, you\u2019d be lucky if they worked 25 percent of the time,\u201d [says](https:\/\/www.wired.com\/2017\/03\/biologists-made-logic-gates-dna\/) Wong.","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"heading3","text":"BLADE in action","format":"markdown","textStyle":"default-heading-3","layout":"heading-layout"},{"role":"body","text":"The team dubbed the new tool with a catchy name, BLADE, which stands for \u201cBoolean logic and arithmetic through DNA excision.\u201d","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"body","text":"But BLADE isn\u2019t just a novelty tool only good at Boolean logic. What it offers is a way to design large-scale biological circuits, so that scientists can reliably control the actions of a cell.","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"body","text":"Wong is already at work finding a project for his new tool, and he has his eyes on regenerative medicine. Although stem cells have the ability to turn into most (if not all) cell types, what they actually become is determined by the set of genes that push them towards a certain fate.","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"body","text":"With BLADE, scientists could design complex if-then systems into stem cells, where one set of \u201cif\u201d conditions pushes the cell towards one fate (say, a neuron), while others trigger it to turn into insulin-producing beta cells.","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"body","text":"BLADE can also give cancer therapy a boost. Scientists are already [engineering immune cells](https:\/\/singularityhub.com\/2016\/06\/26\/75-crispr-targets-cancer-in-first-human-trial-what-you-need-to-know\/) that can detect cancer biomarkers and specifically target cancer cells. Programming additional biocircuits into these cells could give them even more sophistication and control: for example, AND gates would limit the immune cells to only spring into action when they detect multiple cancer markers, further lowering casualties and side effects.","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"body","text":"Although there\u2019s still a ways to go, scientists are hopeful. If we keep addressing the technical challenges in the field, one day we will only be limited \u201cby the imagination of researchers and the number of societal problems and applications that synthetic biology can resolve,\u201d [says](http:\/\/www.nature.com\/nrg\/journal\/v11\/n5\/full\/nrg2775.html) Khalil and Collins.","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"body","text":"One thing is clear: with synthetic biology, we no longer have to play by nature\u2019s rules.","format":"markdown","textStyle":"default-body","layout":"body-layout"},{"role":"body","text":"Image Credit: [Shutterstock](http:\/\/www.shutterstock.com)","format":"markdown","textStyle":"default-body","layout":"body-layout-last"}]}],"componentTextStyles":{"dropcapBodyStyle":{"textAlignment":"left","fontName":"AvenirNext-Regular","fontSize":18,"tracking":0,"lineHeight":24,"textColor":"#4f4f4f","linkStyle":{"textColor":"#428bca"},"paragraphSpacingBefore":18,"paragraphSpacingAfter":18,"dropCapStyle":{"numberOfLines":4,"numberOfCharacters":1,"padding":5,"fontName":"AvenirNext-Bold","textColor":"#4f4f4f","numberOfRaisedLines":0}},"default-body":{"textAlignment":"left","fontName":"AvenirNext-Regular","fontSize":18,"tracking":0,"lineHeight":24,"textColor":"#4f4f4f","linkStyle":{"textColor":"#428bca"},"paragraphSpacingBefore":18,"paragraphSpacingAfter":18},"default-heading-3":{"fontName":"AvenirNext-Bold","fontSize":24,"lineHeight":52,"textColor":"#333333","textAlignment":"left","tracking":0},"default-title":{"fontName":"AvenirNext-Bold","fontSize":48,"lineHeight":52,"tracking":0,"textColor":"#333333","textAlignment":"left"},"default-byline":{"textAlignment":"left","fontName":"AvenirNext-Medium","fontSize":13,"lineHeight":24,"tracking":0,"textColor":"#7c7c7c"}},"componentLayouts":{"body-layout":{"columnStart":0,"columnSpan":6,"margin":{"top":12,"bottom":12}},"body-layout-last":{"columnStart":0,"columnSpan":6,"margin":{"top":12,"bottom":30}},"heading-layout":{"columnStart":0,"columnSpan":6,"margin":{"bottom":15,"top":15}},"headerPhotoLayout":{"ignoreDocumentMargin":true,"columnStart":0,"columnSpan":7},"headerBelowTextPhotoLayout":{"ignoreDocumentMargin":true,"columnStart":0,"columnSpan":7,"margin":{"top":30,"bottom":0}},"title-layout":{"margin":{"top":30,"bottom":0}},"byline-layout":{"margin":{"top":10,"bottom":10},"columnStart":0,"columnSpan":7}},"metadata":{"excerpt":"Our brains are often compared to computers, but in truth, the billions of cells in our bodies may be a better analogy. The squishy sacks of goop may seem a far cry from rigid chips and bundled wires, but cells are experts at taking inputs, running them through a complicated series of logic gates and...","thumbnailURL":"bundle:\/\/scientists-hacked-cells-dna-made-it-a-biocomputer-1.jpg","dateCreated":"2017-04-12T15:00:36+00:00","dateModified":"2017-04-13T18:57:25+00:00","datePublished":"2017-04-12T15:00:36+00:00","canonicalURL":"https:\/\/singularityhub.com\/2017\/04\/12\/scientists-hacked-a-cells-dna-and-made-a-biocomputer-out-of-it\/","generatorIdentifier":"publish-to-apple-news","generatorName":"Publish to Apple News","generatorVersion":"1.2.5"}}