The World Science Festival brings together great minds in science and the arts to produce live and digital content that presents the wonders of science and the drama of scientific discovery to a broad general audience.
Synthetic biology has revolutionized the field of biology in the last two decades. By taking apart natural systems and recombining engineered parts in novel constellations, it has not only unlocked a staggering variety of biological control mechanisms but it has also created a panoply of biomedical achievements, such as innovative diagnostics and therapies. The most common mode of action in the field of synthetic biology is mediated by synthetic gene circuits assembled in a systematic and rational manner. This review covers the most recent therapeutic gene circuits implemented in mammalian and bacterial cells designed for the diagnosis and therapy of an extensive array of diseases. Highlighting new tools for therapeutic gene circuits, we describe a future that holds a plethora of potentialities for the medicine of tomorrow
Since 2008, we witness the emergence of the Do-It-Yourself Biology movement, a global movement spreading the use of biotechnology beyond traditional academic and industrial institutions and into the lay public.
The bioengineering of individual microbial organisms or microbial communities has great potential in agriculture, bioremediation and industry. Understanding community level drivers can improve community level functions to enhance desired outcomes in complex environments, whereas individual microbes can be reduced to a programmable biological unit for specific output goals. While understanding the bioengineering potential of both approaches leads to a wide range of potential uses, public acceptance of such technology may be the greatest hindrance to its application. Public perceptions and expectations of "naturalness", as well as notions of disgust and dread, may delay the development of such technologies to their full benefit. We discuss these bioengineering approaches and draw on the psychological literature to suggest strategies that scientists can use to allay public concerns over the implementation of this technology
The yeast Saccharomyces cerevisiae provides intriguing possibilities for synthetic biology and bioprocess applications, but its use is still constrained by cellular characteristics that limit the product yields. Considering the production of advanced biopharmaceuticals, a major hindrance lies in the yeast endoplasmic reticulum (ER), as it is not equipped for efficient and large scale folding of complex proteins, such as human antibodies. RESULTS: Following the example of professional secretory cells, we show that inducing an ER expansion in yeast by deleting the lipid-regulator gene OPI1 can improve the secretion capacity of full-length antibodies up to fourfold. Based on wild-type and ER-enlarged yeast strains, we conducted a screening of a folding factor overexpression library to identify proteins and their expression levels that enhance the secretion of antibodies. Out of six genes tested, addition of the peptidyl-prolyl isomerase CPR5 provided the most beneficial effect on specific product yield while PDI1, ERO1, KAR2, LHS1 and SIL1 had a mild or even negative effect to antibody secretion efficiency. Combining genes for ER enhancement did not induce any significant additional effect compared to addition of just one element. By combining the Δopi1 strain, with the enlarged ER, with CPR5 overexpression, we were able to boost the specific antibody product yield by a factor of 10 relative to the non-engineered strain. CONCLUSIONS: Engineering protein folding in vivo is a major task for biopharmaceuticals production in yeast and needs to be optimized at several levels. By rational strain design and high-throughput screening applications we were able to increase the specific secreted antibody yields of S. cerevisiae up to 10-fold, providing a promising strain for further process optimization and platform development for antibody production.
Synthetic proteins based on those found in a variety of squid species' ring teeth may lead the way to self-healing polymers carefully constructed for specific toughness and stretchability that might have applications in textiles, cosmetics and...
Teaching Laboratory, Department of Plant Sciences, University of Cambridge Downing Street, Cambridge, CB2 3EA Cambridge, GB
4 Members Attending
"The Amino One Personal Bioreactor Ecosystem is a career-building tool.
The Amino One is a laptop sized Personal Bioreactor and Transformation station that is friendly to use, accessible, and contained. It makes learning and prototyping with genetic engineering and cells accessible to students and teachers. With on-screen instructions that are easy...
Linkage and association studies have mapped thousands of genomic regions that contribute to phenotypic variation, but narrowing these regions to the underlying causal genes and variants has proven much more challenging. Resolution of genetic mapping is limited by the recombination rate. We developed a method that uses CRISPR (clustered, regularly interspaced, short palindromic repeats) to build mapping panels with targeted recombination events. We tested the method by generating a panel with recombination events spaced along a yeast chromosome arm, mapping trait variation, and then targeting a high density of recombination events to the region of interest. Using this approach, we fine-mapped manganese sensitivity to a single polymorphism in the transporter Pmr1. Targeting recombination events to regions of interest allows us to rapidly and systematically identify causal variants underlying trait differences.
Systems metabolic engineering, which recently emerged as metabolic engineering integrated with systems biology, synthetic biology, and evolutionary engineering, allows engineering of microorganisms on a systemic level for the production of valuable chemicals far beyond its native capabilities. Here, we review the strategies for systems metabolic engineering and particularly its applications in Escherichia coli. First, we cover the various tools developed for genetic manipulation in E. coli to increase the production titers of desired chemicals. Next, we detail the strategies for systems metabolic engineering in E. coli, covering the engineering of the native metabolism, the expansion of metabolism with synthetic pathways, and the process engineering aspects undertaken to achieve higher production titers of desired chemicals. Finally, we examine a couple of notable products as case studies produced in E. coli strains developed by systems metabolic engineering. The large portfolio of chemical products successfully produced by engineered E. coli listed here demonstrates the sheer capacity of what can be envisioned and achieved with respect to microbial production of chemicals. Systems metabolic engineering is no longer in its infancy; it is now widely employed and is also positioned to further embrace next-generation interdisciplinary principles and innovation for its upgrade. Systems metabolic engineering will play increasingly important roles in developing industrial strains including E. coli that are capable of efficiently producing natural and nonnatural chemicals and materials from renewable nonfood biomass.
Synthetic biology is characterized by the development of novel and powerful DNA fabrication methods and by the application of engineering principles to biology. The current study describes Terminator Operon Reporter (TOR), a new gene assembly technology based on the conditional activation of a reporter gene in response to sequence errors occurring at the assembly stage of the synthetic element. These errors are monitored by a transcription terminator that is placed between the synthetic gene and reporter gene. Switching of this terminator between active and inactive states dictates the transcription status of the downstream reporter gene to provide a rapid and facile readout of the accuracy of synthetic assembly. Designed specifically and uniquely for the synthesis of protein coding genes in bacteria, TOR allows the rapid and cost-effective fabrication of synthetic constructs by employing oligonucleotides at the most basic purification level (desalted) and without the need for costly and time-consuming post-synthesis correction methods. Thus, TOR streamlines gene assembly approaches, which are central to the future development of synthetic biology.
Did you hear about the secret meeting earlier this month at Harvard Medical School? The one where scientists schemed to create a parentless human being from scratch? Maybe you read one of the skeptical news articles, or the stories illustrated with images from the dystopian sci-fi classic “Blade Runner” or of a robot Frankenstein. One blogger compared the meeting to a gathering of “Bond villains.”
The press coverage was suspicious and critical. Why would a bunch of scientists need to exclude the media and the public from a meeting about something as ethically fraught as synthesizing a human genome?
Three weeks later, the exact details of what happened are still being contested. I’m a researcher in synthetic biology, and I learned of the project from reading the newspaper. I reached out to the meeting’s organizers, who – for reasons I’ll explain – declined to comment for this article. But in conversations with meeting invitees, as well as some critics, I’ve found that much of the press coverage was misleading, and says more about the relationship between journalists and scientists than the meeting itself.
What really happened behind closed doors when over 130 scientists, industry leaders and ethicists convened to talk about synthesizing a human genome? How did these sessions end up so widely misunderstood by the media and the public?
Open doors versus science publishing protocols
The May 10 meeting was titled “HGP-Write: Testing Large Synthetic Genomes in Cells.” HGP refers to the Human Genome Project, the world’s largest collaborative biological effort that resulted in the sequencing of the full human genome in 2003.
Those invited say the organizers hoped to inspire scientists and the public with a new grand challenge project: to advance from reading genomes to writing them, by manufacturing them from individual DNA building blocks. In an invitation dated March 30, the hosts proposed a bold collaborative effort to “synthesize a complete human genome within a cell line.” Panels tackled whether such an effort is worthwhile, as well as the ethical, technological and economic challenges.
The conversation was not intended to be restricted. The meeting organizers – Harvard geneticist George Church; New York University systems geneticist Jef Boeke; Andrew Hessel, of the Bio/Nano research group at Autodesk, Inc.; and Nancy J. Kelley, a lawyer specializing in biotechnology consulting – had plans to engage the broader scientific community, as well as industry, policy makers and the public. They made a video recording of the entire meeting, originally intended to be live-streamed over the Internet. They planned to apply for federal funding, which would invite regulatory oversight. And they submitted a white paper to a major peer-reviewed journal explaining the scientific, technological and ethical aspects of the project.
But the publication of the paper was delayed – the authors haven’t disclosed why, although editors commonly ask for revisions as part of the peer review process. (As of this writing, it has not yet come out.) The organizers are prohibited from discussing the paper in public until it is published – a common journal policy known as an embargo. In deference to the embargo, they declined to comment in detail for this article.
News of the delay came just days before the meeting, and, with dozens of attendees en route, the hosts made a fateful decision. They chose to proceed, but to close the doors to most journalists and ask attendees to delay public discussion until the embargo lifts. (At least one journalist was there – Simone Ross, co-founder of Techonomy Media, confirmed her attendance to me.) “I’m not sure that was the best idea,” Dr. Church told STAT News of the decision to proceed out of the public eye.
The secrecy bred suspicion. “Would it be OK to sequence and then synthesize Einstein’s genome?” asked Stanford bioengineer Drew Endy and Northwestern bioethicist Laurie Zoloth in a joint essay. In theory, an artificial human genome could be used to generate a living human without biological parents. “This idea is an enormous step for the human species, and it shouldn’t be discussed only behind closed doors,” STAT News quoted Dr. Zoloth.
Beyond qualms about the science itself, some observers were concerned that the organizers' decisions - which included seeking industry partners and private funding - were quiet moves towards “privatiz[ing] the current conversation about heritable genetic modification.”
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