 Your new post is loading...
Your new post is loading...
|
Scooped by
Gerd Moe-Behrens
June 26, 2018 3:59 PM
|
Sensory perception often scales logarithmically with the input level. Similarly, the output response of biochemical systems sometimes scales logarithmically with the input signal that drives the system. How biochemical systems achieve logarithmic sensing remains an open puzzle. This article shows how a biochemical logarithmic sensor can be constructed from the most basic principles of chemical reactions. Assuming that reactions follow the classic Michaelis-Menton kinetics of mass action or the more generalized and commonly observed Hill equation response, the summed output of several simple reactions with different sensitivities to the input will often give an aggregate output response that logarithmically transforms the input. The logarithmic response is robust to stochastic fluctuations in parameter values. This model emphasizes the simplicity and robustness by which aggregate chemical circuits composed of sloppy components can achieve precise response characteristics. Both natural and synthetic designs gain from the power of this aggregate approach.
|
|
Scooped by
Gerd Moe-Behrens
June 23, 2018 5:07 PM
|
The origin of biological morphology and form is one of the deepest problems in science, underlying our understanding of development and the functioning of living systems. In 1952, Alan Turing showed that chemical morphogenesis could arise from a linear instability of a spatially uniform state, giving rise to periodic pattern formation in reaction–diffusion systems but only those with a rapidly diffusing inhibitor and a slowly diffusing activator. These conditions are disappointingly hard to achieve in nature, and the role of Turing instabilities in biological pattern formation has been called into question. Recently, the theory was extended to include noisy activator–inhibitor birth and death processes. Surprisingly, this stochastic Turing theory predicts the existence of patterns over a wide range of parameters, in particular with no severe requirement on the ratio of activator–inhibitor diffusion coefficients. To explore whether this mechanism is viable in practice, we have genetically engineered a synthetic bacterial population in which the signaling molecules form a stochastic activator–inhibitor system. The synthetic pattern-forming gene circuit destabilizes an initially homogenous lawn of genetically engineered bacteria, producing disordered patterns with tunable features on a spatial scale much larger than that of a single cell. Spatial correlations of the experimental patterns agree quantitatively with the signature predicted by theory. These results show that Turing-type pattern-forming mechanisms, if driven by stochasticity, can potentially underlie a broad range of biological patterns. These findings provide the groundwork for a unified picture of biological morphogenesis, arising from a combination of stochastic gene expression and dynamical instabilities.
|
|
Scooped by
Gerd Moe-Behrens
June 21, 2018 6:38 PM
|
Mammalian tissue development is an intricate, spatiotemporal process of self-organization
that emerges from gene regulatory networks of differentiating stem cells. A major goal in stem cell biology is to gain a sufficient understanding of gene regulatory networks and cell–cell interactions to...
|
|
Scooped by
Gerd Moe-Behrens
June 19, 2018 7:30 AM
|
Creating a new gene in a single day could soon be possible, thanks to a new technique that mimics the way the body copies its own DNA. Though the technology needs to clear a few more hurdles, it could one day let researchers speedily rewrite microbe genes, enabling them to synthesize new medicines and fuels on the fly.
“It’s the future,” says George Church, a geneticist at Harvard University who has pioneered numerous technologies to read and write DNA for synthetic biology. “This is going to be enormous.”
Researchers have been able to make DNA since the 1970s. The traditional approach takes DNA nucleotides—the chemical letters A, G, C, and T—and adds them, one by one, to a growing chain called an oligonucleotide, or oligo. But the process, which uses a series of toxic organic reagents, is typically slow and error-prone, limiting oligos to about 200 letters—a tiny fraction of the thousands of letters that make up most genes.
Our cells make DNA differently. A variety of enzymes called polymerases read a single strand of DNA and then synthesize a complementary strand that binds to it. That has prompted dreams of re-engineering polymerases to write new DNA.
Over the decades, most researchers have settled on one particular polymerase, called terminal deoxynucleotidyl transferase (TdT), because, unlike other polymerases, it can attach new nucleotides to an oligo strand without following a DNA template strand. Natural TdT does this to write millions of new variations of genes for antibodies, which the immune system can then select from to target invaders. But the natural enzyme adds new DNA letters randomly, rather than controlling the precise sequence of letters as researchers want to do.
Scientists have tried for years to make TdT add one nucleotide at a time and stop, before repeating the process with a different nucleotide, says Sebastian Palluk, a Ph.D. student who worked on the project in chemist Jay Keasling’s lab at the Lawrence Berkeley National Laboratory in California. They started by adding chemical groups to DNA’s four bases that act as “stop” signals. So, when TdT adds a modified A to an oligo of any length, it would be prevented from adding the next base. The oglio is then fished out, washed, and treated with another compound to cut off the blocking group, readying it for the next extension.
But TdT doesn’t work well with these modified nucleotides. “TdT is very picky,” Palluk says. One such system, for example, required about an hour to add each modified base, far too slow to be practical.
Palluk says he also tried to make this approach work. “I went down that route for 2 years,” he says. But he got to talking with Daniel Arlow, a fellow Ph.D. student in Keasling’s lab who was also trying to use enzymes to synthesize DNA. Eventually, the pair settled on a novel approach. They start with four separate pools for the four separate bases, each one with copies of TdT tethered to either A, G, C, or T. To grow their oligo, they add a base from one of the pools. After TdT adds the base to the end of the oligo, it remains tethered, blocking any additional copies of the enzyme from reacting with the oligo and extending it further. The now oligos are then fished out, and the tethers are snipped off. The free TdT is washed away, and the oligo is ready for the next base to be added.
Ultimately, the approach should be cheap, Keasling says, because TdT is easy to manufacture in bacteria and yeast. It’s also fast. Most new nucleotides attach to the growing oligo in 10 to 20 seconds, Palluk, Arlow, Keasling, and their colleagues report today in Nature Biotechnology. For now, the tether snipping step still takes a minute. So synthesizing a whole gene will still likely take the better part of a day.
Church says the new approach is not quite ready to dethrone conventional DNA synthesis. So far, the group has made oligos only 10 bases long. And there are still a few writing problems, as the approach was only 98% accurate at writing DNA in the desired sequence, below the 99% accuracy of the traditional approach. “It’s cool for a first demonstration,” Palluk says. “But it’s not quite there yet.”
In order to write oligos up to 1000 bases long, the approach will likely need to be 99.9% accurate. If it gets there, Church says it could help revolutionize not just synthetic biology’s efforts to write and test new genes, but also enable efforts to write massive libraries of data in DNA to create a compact archive the firehoses of information coming from giant science projects such as astronomy surveys, which could then be fished out and read out later.
|
|
Scooped by
Gerd Moe-Behrens
June 19, 2018 7:25 AM
|
One of the challenges of modern pharmacology is specificity. Despite therapeutic effects, drugs can often have side effects. The biological basis for this has to do with the proteins and receptors that the drug targets and binds to. Many target receptors are connected to more than one biochemical pathway or more commonly, the drug is not specific enough to exclusively bind one particular receptor.
|
|
Scooped by
Gerd Moe-Behrens
June 13, 2018 6:57 PM
|
MIT engineers have developed a probiotic mix of natural and engineered bacteria to diagnose and treat cholera, an intestinal infection that causes severe dehydration.
|
|
Scooped by
Gerd Moe-Behrens
June 9, 2018 4:50 PM
|
Biotechnol Biofuels. 2018 Jun 1;11:152. doi: 10.1186/s13068-018-1153-5. eCollection 2018.Review...
|
|
Scooped by
Gerd Moe-Behrens
June 9, 2018 4:48 PM
|
ACS Synth Biol. 2018 Jun 3. doi: 10.1021/acssynbio.7b00430.[Epub ahead of print]...
|
|
Scooped by
Gerd Moe-Behrens
June 9, 2018 4:45 PM
|
SCALE Studies in Bio Art Wednesday June 13, 2018 6-8PM SVA BFA Fine Arts 335 W 16th St, New York, NY 10011 Participants: Clare Benson Magdalena Dukiewicz Ryan Greer Jane Hsi Keika Okamoto E.R. Saba Bio Art SVA Art and Science Laboratory Bio Art Lab. SVA BFA Fine Arts School of Visual Arts, New York The Bio Art Lab was founded in 2011 as part of the SVA’s BFA Fine Arts new facility consisting of 54,000 square feet in the heart of Chelsea, NYC. The Lab was founded and is directed by Suzanne Anker, Chair of the BFA Fine Arts Department. Conceived as a place where scientific tools and techniques become tools and techniques in art practice, the Lab is the result of many people’s expertise, research and sustained effort. Such deftness and collaborative efforts continue to remain crucial in developing this facility to its full potential. Joe Tekippe and Luis Navarro were responsible for all high-tech computer access including our full range of hardware and software installation and maintenance. More recently Michael Falk has coordinated, experimented with and set up the necessary photographic resources we need in place for our microscopic image making. Daniel Wapner and Sung Jin Choi used their skills to seamlessly build both stainless steel and aluminum stands housing our fish and plants. Mark Rosen set up a check-in check-out system for our library. Brandon Ballengée added his knowledge concerning fresh water fish and frog tanks in addition to the acquisition of a chemical hood where the preservation of specimens and cleaning and staining of aquatic animals could take place. Dr. Ignacio Lopez-Coviella was a great consultant in developing our microscopic practices, pointing us in the direction of three types of microscopes: a compound microscope, a dissecting microscope and an inverted microscope. Marine biologist Joe Di Giorgis expanded our collection of microscopes by loaning us a full array of dissecting microscopes and analyzing the camera requirements for each. Molecular scientists, Oliver Medvedik and Ellen Jorgensen from Genspace consulted in regard to our incubators, HEPA filter and autoclave as well as helping to design projects relevant to Bio Art practice. Ellen and Oliver are also our current “scientists in residence” working with students on the use of bio-materials for art projects and the barcoding of plants from the surrounding environment. Tarah Rhoda researched labware, lab rules and formats for molecular cuisine and tissue culturing as well as lighting systems for plants and lab protocol, safety and workflow. Many student workers were instrumental in maintaining the live plants and organisms in the Lab with care, integrity, and enthusiasm. And I say the same for the various visiting artists who have shared their expertise with us (see separate link.) Scott Vaughn of NY Aquarium in NYC manages our salt water aquarium which houses coral, an anemone, hermit crabs and starfish. Sebastian Cocioba from NY Botanics, introduced techniques for plant tissue culturing of African violets and venus fly-traps. He is also developing an “SVA” palette for painting with bacteria. Sebastian and Sung have been helping us develop a molecular biology component of our lab employing PCR practices, synthetic biology and forensics in analyzing molecular data. Raul Gomez Valverde has designed our micro website, www.bioart.sva.edu, and has produced outstanding pictures of student works produced in situ. George Boorujy has donated marvelous taxidermied duck specimens which appear as if in flight. And of course our great thanks to President David Rhodes and Provost Jeff Nesin for allowing us to go forward with this great resource.
|
|
Scooped by
Gerd Moe-Behrens
May 31, 2018 4:21 PM
|
A common theme in the self-organization of multicellular tissues is the use of cell-cell signaling networks to induce morphological changes. We used the modular synNotch juxtacrine signaling platform to engineer artificial genetic programs in which specific cell-cell contacts induced changes in cadherin cell adhesion. Despite their simplicity, these minimal intercellular programs were sufficient to yield assemblies with hallmarks of natural developmental systems: robust self-organization into multi-domain structures, well-choreographed sequential assembly, cell type divergence, symmetry breaking, and the capacity for regeneration upon injury. The ability of these networks to drive complex structure formation illustrates the power of interlinking cell signaling with cell sorting: signal-induced spatial reorganization alters the local signals received by each cell, resulting in iterative cycles of cell fate branching. These results provide insights into the evolution of multi-cellularity and demonstrate the potential to engineer customized self-organizing tissues or materials.
|
|
Scooped by
Gerd Moe-Behrens
May 24, 2018 6:23 PM
|
SynBioBeta 2018 comes to San Francisco on October 1-3, uniting biological engineers, entrepreneurs and investors for the Global Synthetic Biology Summit. Meet over 1000 attendees and 100 speakers, sponsors and exhibitors.
|
|
Scooped by
Gerd Moe-Behrens
May 21, 2018 2:53 PM
|
A synthetic biologist from NASA plans to make CRISPR-based genetic engineering as accessible as a home science kit, so you can bio-hack yeast and bacteria on your kitchen bench....
|
|
Scooped by
Gerd Moe-Behrens
May 19, 2018 6:18 PM
|
Bio Protoc. 2018 Mar 20;8(6). pii: e2765. doi: 10.21769/BioProtoc.2765.
|
|
|
Scooped by
Gerd Moe-Behrens
June 23, 2018 5:08 PM
|
Microbiol Spectr. 2018 May;6(3). doi: 10.1128/microbiolspec.RWR-0007-2017.
|
|
Scooped by
Gerd Moe-Behrens
June 23, 2018 5:06 PM
|
|
|
Scooped by
Gerd Moe-Behrens
June 21, 2018 6:30 PM
|
On the path to an artificial cell
|
|
Scooped by
Gerd Moe-Behrens
June 19, 2018 7:29 AM
|
Frustrated at the slow pace of putting code together, two young researchers took things into their own hands. Elizabeth Finkel reports.
|
|
Scooped by
Gerd Moe-Behrens
June 18, 2018 4:57 PM
|
Get the latest in biotechnology through daily news coverage as well as analysis, features, tutorials, webinars, podcasts, and blogs. Learn about the entire bioproduct life cycle from early-stage R&D, to applied research including omics, biomarkers, as well as diagnostics, to bioprocessing and...
|
|
Scooped by
Gerd Moe-Behrens
June 11, 2018 4:05 PM
|
Scientists have developed a way to use machine learning to dramatically accelerate the design of microbes that produce biofuel....
|
|
Scooped by
Gerd Moe-Behrens
June 9, 2018 4:48 PM
|
Journal of Biosensors and Bioelectronics discusses the latest research innovations and important developments in this field.
|
|
Scooped by
Gerd Moe-Behrens
June 9, 2018 4:47 PM
|
Biotechnol J. 2018 Jun 3:e1800121. doi: 10.1002/biot.201800121.[Epub ahead of print]...
|
|
Scooped by
Gerd Moe-Behrens
June 2, 2018 6:05 PM
|
Living cells are highly complex systems comprising a multitude of elements that are engaged in the many convoluted processes observed during the cell cycle. However, not all elements and processes are essential for cell survival and reproduction under steady-state environmental conditions.
|
|
Scooped by
Gerd Moe-Behrens
May 27, 2018 11:18 AM
|
Living organisms are differentiated by their genetic material-millions to billions of DNA bases encoding thousands of genes. These genes are translated into a vast array of proteins, many of which have functions that are still unknown. Previously, it was believed that simply knowing the genetic sequence of an organism would be the key to unlocking all understanding. However, as DNA sequencing technology has become affordable, it has become clear that living cells are governed by complex, multilayered networks of gene regulation that cannot be deduced from sequence alone. Synthetic biology as a field might best be characterized as a learn-by-building approach, in which scientists attempt to engineer molecular pathways that do not exist in nature. In doing so, they test the limits of both natural and engineered organisms.
|
|
Scooped by
Gerd Moe-Behrens
May 23, 2018 6:36 PM
|
Cell-penetrating assembly uncages hormone, turning on gene circuit...
|
|
Scooped by
Gerd Moe-Behrens
May 20, 2018 6:57 PM
|
fabrication platform - In her water-based digital fabrication platform project, architect and professor Neri Oxman embraces water as nature’s architectural tool and...
|
Scoop.it!
