It all began in 1891, when Dr. William B. Coley, a bone sarcoma surgeon at the Memorial Hospital in New York, injected streptococcal organisms into a patient with inoperable cancer. He thought that the infection he induced would have the
The University of Manchester (press release) Spinout to pursue commercial production of bio-propane through synthetic biology The University of Manchester (press release) Spinout to pursue commercial production of bio-propane through synthetic...
Not unlike the booming technology companies that launched in Silicon Valley garages decades ago, the next step in the evolution of synthetic biology is being built by citizen scientists in their homes or communal labs. One local man is hoping to bring this new wave of scientific exploration to Charlottesville. Scientists and science enthusiasts are breaking from traditional laboratory environments to practice a variety of scientific disciplines in their garages and kitchens, conducting their own projects and using their own hardware. As this movement continues to grow, lab spaces for members of the community have begun popping up in densely populated cities around the country — and soon, Charlottesville may have one of its own for do-it-yourself biology, or biohacking.
Proteins embody epitopes that serve as their antigenic determinants. Epitopes occupy a central place in integrative biology, not to mention as targets for novel vaccine, pharmaceutical, and systems diagnostics development. The presence of T-cell and B-cell epitopes has been extensively studied due to their potential in synthetic vaccine design. However, reliable prediction of linear B-cell epitope remains a formidable challenge. Earlier studies have reported discrepancy in amino acid composition between the epitopes and non-epitopes. Hence, this study proposed and developed a novel amino acid composition-based feature descriptor, Dipeptide Deviation from Expected Mean (DDE), to distinguish the linear B-cell epitopes from non-epitopes effectively. In this study, for the first time, only exact linear B-cell epitopes and non-epitopes have been utilized for developing the prediction method, unlike the use of epitope-containing regions in earlier reports. To evaluate the performance of the DDE feature vector, models have been developed with two widely used machine-learning techniques Support Vector Machine and AdaBoost-Random Forest. Five-fold cross-validation performance of the proposed method with error-free dataset and dataset from other studies achieved an overall accuracy between nearly 61% and 73%, with balance between sensitivity and specificity metrics. Performance of the DDE feature vector was better (with accuracy difference of about 2% to 12%), in comparison to other amino acid-derived features on different datasets. This study reflects the efficiency of the DDE feature vector in enhancing the linear B-cell epitope prediction performance, compared to other feature representations. The proposed method is made as a stand-alone tool available freely for researchers, particularly for those interested in vaccine design and novel molecular target development for systems therapeutics and diagnostics: https://github.com/brsaran/LBEEP.
Recent advances in synthetic biology call for robust, flexible and efficient in silico optimization methodologies. We present a Pareto design approach for the bi-level optimization problem associated to the overproduction of specific metabolites in Escherichia coli. Our method efficiently explores the high dimensional genetic manipulation space, finding a number of trade-offs between synthetic and biological objectives, hence furnishing a deeper biological insight to the addressed problem and important results for industrial purposes. We demonstrate the computational capabilities of our Pareto-oriented approach comparing it with state-of-the-art heuristics in the overproduction problems of i) 1,4-butanediol, ii) myristoyl-CoA, i ii) malonyl-CoA , iv) acetate and v) succinate. We show that our algorithms are able to gracefully adapt and scale to more complex models and more biologically-relevant simulations of the genetic manipulations allowed. The Results obtained for 1,4-butanediol overproduction significantly outperform results previously obtained, in terms of 1,4-butanediol to biomass formation ratio and knock-out costs. In particular overproduction percentage is of +662.7%, from 1.425 mmolh-1gDW-1 (wild type) to 10.869 mmolh-1gDW-1, with a knockout cost of 6. Whereas, Pareto-optimal designs we have found in fatty acid optimizations strictly dominate the ones obtained by the other methodologies, e.g., biomass and myristoyl-CoA exportation improvement of +21.43% (0.17 h-1) and +5.19% (1.62 mmolh-1gDW-1), respectively. Furthermore CPU time required by our heuristic approach is more than halved. Finally we implement pathway oriented sensitivity analysis, epsilon-dominance analysis and robustness analysis to enhance our biological understanding of the problem and to improve the optimization algorithm capabilities.
There is a general assent on the key role of standards in Synthetic Biology. In two consecutive letters to this journal, suggestions on the assembly methods for the Registry of standard biological parts have been described. We fully agree with those authors on the need of a more flexible building strategy and we highlight in the present work two major functional challenges standardization efforts have to deal with: the need of both universal and orthogonal behaviors. We provide experimental data that clearly indicate that such engineering requirements should not be taken for granted in Synthetic Biology.
iGEM Grand Prize: Try to grasp 'the magnitude of what they have achieved'William and Mary NewsAn interdisciplinary team of William & Mary students have brought home one of the biggest prizes in synthetic biology, an honor that has been called the...
Reverse engineering of biological pathways involves an iterative process between experiments, data processing, and theoretical analysis. Despite concurrent advances in quality and quantity of data as well as computing resources and algorithms, difficulties in deciphering direct and indirect network connections are prevalent. Here, we adopt the notions of abstraction, emulation, benchmarking, and validation in the context of discovering features specific to this family of connectivities. After subjecting benchmark synthetic circuits to perturbations, we inferred the network connections using a combination of nonparametric single-cell data resampling and modular response analysis. Intriguingly, we discovered that recovered weights of specific network edges undergo divergent shifts under differential perturbations, and that the particular behavior is markedly different between topologies. Our results point to a conceptual advance for reverse engineering beyond weight inference. Investigating topological changes under differential perturbations may address the longstanding problem of discriminating direct and indirect connectivities in biological networks.
As scientists make strides toward the goal of developing a form of biological engineering that?s as predictive and reliable as chemical engineering is for chemistry, one technology component has become absolutely critical: gene synthesis. Gene synthesis is the process of building stretches of deoxyribonucleic acid (DNA) to order?some stretches based on DNA that exists already in nature, some based on novel designs intended to accomplish new functions. This process is the foundation of synthetic biology, which is rapidly becoming the engineering counterpart to biology.
Scientists in Boston have come up with a twist on an important method for “editing” genomes that could give researchers added control over the DNA of living things and influence a raging patent dispute over the powerful techniques.
Feng Zhang, a researcher at the Broad Institute of MIT and Harvard, reported today in the journal Cell that he had developed a replacement for a key component of the genome-engineering system commonly known as CRISPR-Cas9.
The gene-editing technology, which snips DNA at precise locations, has swept through science labs because it provides a versatile, potent way to engineer the DNA of bacteria, plants, and humans. It is allowing scientists to broadly reimagine how they study everything from Alzheimer’s disease to biotech crops.
The work by Zhang’s team, carried out this year, shows that the cutting protein Cas9 can be replaced by a different protein, Cpf1, which he says will also work as a versatile editing tool. In a carefully crafted press release, Broad chief Eric Lander said the system “represents a new generation of genome editing technology” that has “dramatic potential to advance genetic engineering.”
Compartmentalization is one of the defining features of life. Through intracellular spatial control, cells are able to organize and regulate their metabolism. One of the most broadly used organizational principles in nature is encapsulation. Cellular processes can either be encapsulated within membrane-bound organelles or proteinaceous compartments that create distinct microenvironments optimized for a given task. Further challenges addressed through intracellular compartmentalization are toxic or volatile pathway intermediates, slow turnover rates, and competing side reactions. This review highlights a selection of naturally occurring membrane- and protein-based encapsulation systems in microbes and their recent applications and emerging opportunities in synthetic biology. We focus on examples that use engineered cellular organization to control metabolic pathway flux for the production of useful compounds and materials.
IF YOU WANT to drop some real DNA editing knowledge—like, I don’t know, at a party!—here’s a tip. Instead of calling the much hyped precise genome-editing tool CRISPR, call it CRISPR/Cas9. CRISPR, you see, just refers to stretches of repeating DNA that sit near the gene for Cas9, the actual protein that does the DNA editing.
Well, at least for now. Today, gene-editing scientists dropped some curious news: They’ve found a CRISPR system involving a different protein that also edits human DNA, and, in some cases, it may work even better than Cas9.
The discovery comes at a time when CRISPR/Cas9 is sweeping through biology labs. So revolutionary is this new genome editing technique that rival groups, who each claim to have been first to the tech, are bitterly fighting over the CRISPR/Cas9 patent. This new gene-editing protein called Cpf1—and maybe even others yet to be discovered—means that one patent may not be so powerful after all.
And there’s good reason to think more useful CRISPR proteins are out there. CRISPR sequences are a part of primordial immune systems, found in some 40 percent of bacteria and 90 percent of archaea. In a study published today in Cell, Feng Zhang (no relation to this writer) and colleagues trawled through bacterial genomes looking for different versions of Cpf1. They found two, from Acidominococcus and Lachnospiraceae, that can snip DNA when scientists insert them into human cells.
“There are definitely many more defense systems out there, and maybe some of them might even have spectacular applications like with the Cas9 system,” says John van der Oost, a microbiologist at Wageningen University who is a co-author on the paper. “We have the feeling it’s just the tip of the iceberg.”
Zhang and van der Oost’s search was deliberate, but the initial discovery of CRISPR/Cas9 as a gene-editing tool was not. Back in the 1980s, microbiologists saw strange repeating sequences in the DNA of bacteria. Those clustered regularly interspaced short palindromic repeats became CRISPR, and scientists realized they were evidence of an immune system bacteria used to defend against viruses. The spacers between the repeats are in fact snippets of viral genomes, which CRISPR-associated proteins called Cas use as “mug shots” to recognize viruses and shred their DNA.
Many different proteins are associated with CRISPR. But in the early 2010s, Emmanuelle Charpentier, who was studying the flesh-eating bacteria Streptococcus pyogenes, stumbled onto one with special powers. Her bacteria happen to carry Cas9 proteins, which have the remarkable ability to precisely cut DNA based on a RNA guide sequence. In 2012, Charpentier and UC Berkeley biologist Jennifer Doudna published a paper describing the CRISPR/Cas9 system and speculated about its genome editing capabilities. And they filed a patent application. Much more on that patent later.
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