Collaborating with designers, who sometimes take a highly conceptual approach, can help scientists to envisage exciting new ideas and applications. A good example of this is the work of Victoria Geaney, a designer who worked with synthetic biology students at Imperial College London to bring together the worlds of Fashion and Science. Victoria came to the University of Cambridge on the 30th of October to give a lecture, so we thought it would be a good opportunity to send Sarah Sewell to investigate:
The students in Anthony James’s basement insectary at the University of California, Irvine, knew they’d broken the laws of evolution when they looked at the mosquitoes’ eyes.
By rights, the bugs, born from fathers with fluorescent red eyes and mothers with normal ones, should have come out only about half red. Instead, as they counted them, first a few and then by the hundreds, they found 99 percent had glowing eyes.
More important than the eye color is that James’s mosquitoes also carry genes that stop the malaria parasite from growing. If these insects were ever released in the wild, their “selfish” genetic cargo would spread inexorably through mosquito populations, and potentially stop the transmission of malaria.
The technology, called a “gene drive,” was built using the gene-editing technology known as CRISPR and is being reported by James, a specialist in mosquito biology, and a half dozen colleagues today in the Proceedings of the National Academy of Sciences.
A functioning gene drive in mosquitoes has been anticipated for more than a decade by public health organizations as a revolutionary novel way to fight malaria. Now that it’s a reality, however, the work raises questions over whether the technology is safe enough to ever be released into the wild.
“This is a major advance because it shows that gene drives will likely be effective in mosquitoes,” says Kevin Esvelt, a gene drive researcher at Harvard University’s Wyss Institute. “Technology is no longer the limitation.”
Starting last summer, Esvelt and other scientists began warning that gene drives were about to jump from theory to reality (see “Protect Society from Our Inventions, Says Genome Editing Scientists”) and needed more attention by regulators and the public. The National Academy of Sciences is studying the science and ethics of the technology and plans to release recommendations next year on “responsible conduct” by scientists and companies.
Gene drives are just the latest example of the fantastic power of CRISPR editing to alter the DNA of living things, which has already set off a debate over the possibility that gene editing could be used to generate designer human babies (see “Engineering the Perfect Baby”). But Henry Greely, a law professor and bioethics specialist at Stanford, says environmental uses are more worrisome than a few modified people. “The possibility of remaking the biosphere is enormously significant, and a lot closer to realization,” he says.
Malaria is caused when a mosquito bite transmits plasmodium, a single-celled parasite. It’s treatable, yet every year, 670,000 people die from malaria, the majority of them young children in sub-Saharan Africa.
James says his mosquitoes are the culmination of decades of mostly obscure, unheralded work by a few insect specialists toward constructing a genetic solution to malaria. It finally became possible this year when scientists in the laboratory of Ethan Bier, a fly biologist at the University of California, San Diego, who is a coauthor of the paper, finally used CRISPR to perfect a molecular “motor” that could allow the anti-malaria genes to spread.
The mosquitoes have two important genetic additions. One is genes that manufacture antibodies whenever a female mosquito has a “blood meal.” Those antibodies bind to the parasite’s surface and halt its development. Yet normally, such an engineered mosquito would pass the genes only to exactly half its offspring, since there’s a 50 percent chance any chunk of DNA would come from its mate. And since the new genes probably don’t help a mosquito much, they’d quickly peter out in the wild.
That’s where CRISPR comes in. In a gene drive, components of the CRISPR system are added such that any normal gene gets edited and the genetic cargo is added to it as well. In James’s lab, practically all the mosquitoes ended up with the genetic addition, a result Esvelt calls “astounding.”
What worries Esvelt is that, in his opinion, the California researchers haven’t used strict enough safety measures. He says locked doors and closed cages aren’t enough. He wants them to install a genetic “reversal drive” so the change can be undone, if necessary. “An accidental release would be a disaster with potentially devastating consequences for public trust in science and especially gene-drive interventions,” he says. “No gene-drive intervention must ever be released without popular support.”
James says the experiment was safe since the mosquitoes are kept behind a series of locked, card-entry doors and because they aren’t native to California. If any escaped, they wouldn’t be able to reproduce.
In fact, the whole point of a gene drive is to release it into the wild, a concept that has long been accepted, at least in theory, by public health organizations including the Gates Foundation. Now that they’re actually possible, however, alarming news headlines have compared the technology to “the next weapon of mass destruction” and even raised the specter of insect terrorism, such as mosquitoes that kill people with a toxin.
Gene-drive terrorism is probably nonsense, at least for now. That’s because even if insect weapons were possible, in practice it’s unlikely a terrorist organization would invest millions in an advanced genetic-engineering program. “I have been thinking quite a bit about bad things you could do with it, and we haven’t come up with anything that would succeed,” says Bier. “There are so many bad things you could do that are easier.”
Instead, Bier and James say they are convinced that engineered mosquitoes should be released as soon as possible, something they hope to do if they can find a community affected by malaria that will agree to it. “Imagine we could design a mosquito that would magically cure cancer,” says Bier. “Well, the fear of getting malaria is the same fear we have of getting cancer. In my opinion the benefits outweigh the risks, and we should move forward as aggressively as we can.”
It is distressing, but a fact, that the more rapidly any technology is adopted by scientists the more likely it is to leave people confused, anxious, and suspicious. This week, I wrote an article for the magazine about just such a revolutionary technique, called CRISPR, that permits scientists to edit the DNA of plants and animals with an ease and a precision that even a decade ago seemed inconceivable.
CRISPR research has already begun to transform molecular biology. There have been bold new claims about its promise and powers nearly every day. Yet, for the past fifty years, at least since Watson and Crick demonstrated that DNA contained the blueprints required to build everything alive, modern science has been caught in a hype trap. After all, if we possess such exquisitely detailed instructions, shouldn’t they be able to help us fix the broken genes that cause so many of our diseases?
The assumption has long been that the answer is yes. And for decades, we have been told (by the medical establishment, by pharmaceutical companies, and, sadly, by the press) that our knowledge of genetics will soon help us solve nearly every malady, whether it affects humans, other animals, or plants.
It turns out, however, that genetics and magic are two different things. Deciphering the blueprints in the three billion pairs of chemical letters which make up the human genome has been even more complex than anyone had imagined. And even though the advances have been real, and often dramatic, it doesn’t always seem that way. This has led many people to discount, and even fear, our most promising technologies. Somehow, we take lessons more readily from movies like “Jurassic Park” and “Gattaca” than from the very real, though largely incremental, advances in medical treatments.
This dangerous disconnect between scientific possibility and tangible results has already caused great harm: a scientifically unjustified fear of G.M.O.s, for example, has prevented many potentially life-enhancing crops from even being tested, let alone planted widely. The death of one patient, in 1999, halted all human-gene-therapy experiments in the United States for several years. We should, of course, be exceedingly cautious with such research, but if the U.S. is going to stop studies that could potentially help millions of people there are costs to that, too. (It’s worth remembering that there are real risks to everything we do: aspirin kills hundreds of Americans every year, and in the first half of 2015 nearly twenty thousand people have died in car accidents.)
Because it makes manipulating genes so much easier, CRISPR offers researchers the ability to rapidly accelerate studies of many types of illness, including cancers, autism, and AIDS. It will also make it possible to alter the genes of plants so that they can resist various diseases (without introducing the DNA of a foreign organism, which is how G.M.O.s are made). With CRISPR, almost anything could become possible: You want a unicorn? Just tweak the horse genome. How about a truly blue rose? The gene for the blue pigment does not exist naturally in roses. With CRISPR, it should be a trivial matter simply to edit that gene in.
Eventually, CRISPR should also permit technicians to edit embryos, which, at least in theory, could change the genetic lineage of mankind. The prospect is at least as frightening as it is exciting, and we need to start talking about that now. In the press, at least, that conversation—about perhaps the most exciting advance in the history of molecular biology—seems to have started. Two of the researchers I focussed on in my piece for The New Yorker have also been featured in other publications in the past two weeks: the Times has a profile of Jennifer Doudna, the Berkeley biochemist who helped figure out how to program CRISPR molecules to edit DNA, and STAT, a new online health and science publication launched by the Boston Globe’s owner, has one about Feng Zhang, a pioneering biologist at the Broad Institute of Harvard and M.I.T., who first made the technology work in mammals. The subject will soon get even more attention. Early next month, the National Academy of Sciences will convene an international conference devoted to the ethical use of this powerful new tool.
Proteins and synthetic polymers that undergo aqueous phase transitions mediate self-assembly in nature and in man-made material systems. Yet little is known about how the phase behaviour of a protein is encoded in its amino acid sequence. Here, by synthesizing intrinsically disordered, repeat proteins to test motifs that we hypothesized would encode phase behaviour, we show that the proteins can be designed to exhibit tunable lower or upper critical solution temperature (LCST and UCST, respectively) transitions in physiological solutions. We also show that mutation of key residues at the repeat level abolishes phase behaviour or encodes an orthogonal transition. Furthermore, we provide heuristics to identify, at the proteome level, proteins that might exhibit phase behaviour and to design novel protein polymers consisting of biologically active peptide repeats that exhibit LCST or UCST transitions. These findings set the foundation for the prediction and encoding of phase behaviour at the sequence level.
Motivation: An important problem in synthetic biology is to design a nucleotide sequence of an mRNA that confers a desirable expression level of a target protein. The secondary structure of protein-coding sequences (CDSs) is one potential factor that could have both positive and negative effects on protein production. To elucidate the role of secondary structure in CDSs, algorithms for manipulating secondary structure should be developed.
Results: We developed an algorithm for designing a CDS with the most stable secondary structure among all possible ones translated into the same protein, and implemented it as the program CDSfold. The algorithm runs the Zuker algorithm under the constraint of a given amino acid sequence. The time and space complexity is O(L3) and O(L2), respectively, where L is the length of the CDS to be designed. Although our algorithm is slower than the original Zuker algorithm, it could design a relatively long (2.7-kb) CDS in approximately 1 h.
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If you enjoy hacking 3D printers, consider joining us this Wednesday (18th) 6pm at the Panton Arms to discuss 3D printing cellulose! Tom Torode sends the following message:
I’m a biochemist that works on the cell walls of plants and algae. I’ve recently been working on a cool way to solubilise cellulose in a functional form and wo...
The engineering ideal of Synthetic Biology presupposes that standard, interchangeable parts with a predictive behaviour compose organisms. In one word, organisms are literally recognized as machines. Yet living objects are the result of evolutionary processes without any purposiveness, not of a design by external agents. Biological components show massive overlapping and functional degeneracy, standard-free complexity, intrinsic variation and context dependent performances. However, although organisms are not full-fledged machines, synthetic biologists may still be eager for machine-like behaviours out of artificially modified biosystems.
The essential feature of the genetic code is the strict one-to-one correspondence between codons and amino acids. The canonical code consists of three stop codons and 61 sense codons that encode 20% of the amino acid repertoire observed in nature. It was originally designated as immutable and universal due to its conservation in most organisms, but sequencing of genes from the human mitochondrial genomes revealed deviations in codon assignments. Since then, alternative codes have been reported in both nuclear and mitochondrial genomes and genetic code engineering has become an important research field. Here, we review the most recent concepts arising from the study of natural non-standard genetic codes with special emphasis on codon re-assignment strategies that are relevant to engineering genetic code in the laboratory. Recent tools for synthetic biology and current attempts to engineer new codes for incorporation of non-standard amino acids are also reviewed in this article.
Joe Davis is an artist who works not only with paints or pastels, but also with genes and bacteria. In 1986, he collaborated with geneticist Dan Boyd to encode a symbol for life and femininity into an E. coli bacterium. The piece, called Microvenus, was the first artwork to use the tools and techniques of molecular biology. Since then, bioart has become one of several contemporary art forms (including reclamation art and nanoart) that apply scientific methods and technology to explore living systems as artistic subjects. A review of the field, published November 23, can be found in Trends in Biotechnology. Bioart ranges from bacterial manipulation to glowing rabbits, cellular sculptures, and—in the case of Australian-British artist Nina Sellars—documentation of an ear prosthetic that was implanted onto fellow artist Stelarc's arm. In the pursuit of creating art, practitioners have generated tools and techniques that have aided researchers, while sometimes crossing into controversy, such as by releasing invasive species into the environment, blurring the lines between art and modern biology, raising philosophical, societal, and environmental issues that challenge scientific thinking. "Most people don't know that bioart exists, but it can enable scientists to produce new ideas and give us opportunities to look differently at problems," says author Ali K. Yetisen, who works at Harvard Medical School and the Wellman Center for Photomedicine, Massachusetts General Hospital. "At the same time there's been a lot of ethical and safety concerns happening around bioart and artists who wanted to get involved in the past have made mistakes." The Evolution of Bioart In between experiments, Alexander Fleming would paint stick figures and landscapes on paper and in Petri dishes using bacteria. In 1928, after taking a brief hiatus from the lab, he noticed that portions of his "germ paintings," had been killed. The culprit was a fungus, penicillin—a discovery that would revolutionize medicine for decades to come. In 1938, photographer Edward Steichen used a chemical to genetically alter and produce interesting variations in flowering delphiniums. This chemical, colchicine, would later be used by horticulturalists to produce desirable mutations in crops and ornamental plants. In the late 18th and early 19th centuries, the arts and sciences moved away from traditionally shared interests and formed secular divisions that persisted well into the 20th century. "Appearance of environmental art in the 1970s brought about renewed awareness of special relationships between art and the natural world," Yetisen says.
Bioart is a creative practice that adapts scientific methods and draws inspiration from the philosophical, societal, and environmental implications of recombinant genetics, molecular biology, and biotechnology. Some bioartists foster interdisciplinary relationships that blur distinctions between art and science. Others emphasize critical responses to emerging trends in the life sciences. Since bioart can be combined with realistic views of scientific developments, it may help inform the public about science. Artistic responses to biotechnology also integrate cultural commentary resembling political activism. Art is not only about ‘responses’, however. Bioart can also initiate new science and engineering concepts, foster openness to collaboration and increasing scientific literacy, and help to form the basis of artists’ future relationships with the communities of biology and the life sciences.
The creation of complex systems whether electronic, mechanic, chemical, or biological can prove incredibly challenging. In this talk, I will outline my vision for "Bio-Design Automation" for synthetic biology.
The introduction of open source in the life sciences is increasingly being suggested as an alternative to patenting. This is an alternative, however, that takes its shape at the intersection of the life sciences and informatics. Numerous examples can be identified wherein open source in the life sciences refers to access, sharing and collaboration as informatic practices. This includes open source as an experimental model and as a more sophisticated approach of genetic engineering. The first section discusses the greater flexibly in regard of patenting and the relationship to the introduction of open source in the life sciences. The main argument is that the ownership of knowledge in the life sciences should be reconsidered in the context of the centrality of DNA in informatic formats. This is illustrated by discussing a range of examples of open source models. The second part focuses on open source in synthetic biology as exemplary for the re-materialization of information into food, energy, medicine and so forth. The paper ends by raising the question whether another kind of alternative might be possible: one that looks at open source as a model for an alternative to the commodification of life that is understood as an attempt to comprehensively remove the restrictions from the usage of DNA in any of its formats.
We are developing and implementing computational-experimental methods to reverse engineer and analyze gene regulatory network in microbes and higher organisms. We are designing and constructing synthetic gene networks for a variety of biotechnology and bioenergy applications. We are also using engineered gene networks to study general principles underlying gene regulation.
Combinatorial assembly of DNA elements is an efficient method for building large-scale synthetic pathways from standardized, reusable components. These methods are particularly useful because they enable assembly of multiple DNA fragments in one reaction, at the cost of requiring that each fragment satisfy design constraints. We developed BIOPARTSBUILDER as a biologist-friendly web tool to design biological parts that are compatible with DNA combinatorial assembly methods, such as Golden Gate and related methods. It retrieves biological sequences, enforces compliance with assembly design standards, and provides a fabrication plan for each fragment.
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