News from the Wyss Institute -- In the Pipeline
Good news and bad news on antibiotic resistance
Core Faculty member Jim Collins and his team are hot on the trail of antibiotic-resistant bacteria and recently reported two major studies in one month about this serious public-health issue. In Nature, they revealed part of what makes these bacteria so tough to beat: viruses in the gut actually serve as allies by handing them genes that confer antibiotic resistance. That's the bad news. The good news, which Collins' team reported in Science Translational Medicine, is that treating bacteria with a silver compound boosts the efficacy of four existing antibiotics. These findings help pave the way toward new therapies for drug-resistant and recurrent infections.
Wrinkles that we want
Inspired by the wrinkling patterns that work various optical wonders in Nature, such as the iridescent cuticle of certain beetles and octopi that change color to avoid predators, Wyss Institute researchers led by Core Faculty member Joanna Aizenberg can now fine-tune the optical properties of a flexible polymer by applying varying degrees of mechanical strain. The results, reported in Advanced Optical Materials, could herald the development of new types of low-cost dynamic privacy screens, encryption devices, and smart window technologies. More...
The Goldilocks of hydrogels?
Scientists have been trying for years to design biocompatible materials that are "just right" for tissue-engineering applications -- flexible, not too hard to make, and stable enough to support cell growth. A team led by Associate Faculty member Ali Khademhosseini and Postdoctoral Fellow Nasim Annabi has designed a new hydrogel that may do the trick. It incorporates an elastic protein found in all human tissues, the team reported in dual publications in Biomaterials and Advanced Functional Materials. More...
New moxie for microPADs
A team led by Core Faculty member George Whitesides reports in Lab on a Chip a new bench-top technique that can fabricate paper-based, microfluidic devices with exciting potential in low-cost medical diagnostics, environmental monitoring, food safety testing, and more. The researchers used a craft-cutting tool to etch channels as narrow as 45 µm in the paper devices, which can be designed and fabricated in less than ten minutes. The devices could help analyze complex fluids such as whole blood or droplets of water in oil -- a key advantage over existing microfluidic paper-based analytical devices (µPADs).
Flowers assemble in beaker
In a feat of bioinspiration, a team led by Core Faculty member Joanna Aizenberg created precisely tailored crystal structures in a beaker of fluid, as reported in Science. They grew a veritable garden of microscopic crystals, achieving shapes resembling tulips, marigolds, and carnations by subjecting a water-based barium chloride and sodium silicate solution to tightly controlled variables of pH, temperature, and air exposure. Chemical gradients influence the way many organisms grow, much as calcium carbonate gradients influence the growth of marine mollusks.This novel advancement in self-assembly signifies new capabilities in bioinspired engineeringMore..."Our vision is to build as organisms do," Aizenberg said.
Growing bone from silicate nanoplatelets
A team led by Associate Faculty member Ali Khademhosseini and Postdoctoral Fellow Akhilesh K. Gaharwar reported recently in Advanced Materials that silicate nanoplatelets can stimulate stem cells to form into bone tissue in the absence of growth factors.The disk-shaped synthetic silicate nanoplatelets have been used extensively as food additives, cements, filler material, and other industrial applications -- but never before for tissue engineering or any other medical application. These robust nanoparticles dissociate into non-toxic products that each play a role in bone-related growth processes.
Hot springs may harbor key to better biofuels
Wyss researchers, led by Wyss Postdoctoral Fellow Matt Mattozzi, are drawing inspiration -- and genetic sequences -- from a bacterium that lives in hot springs and carries out photosynthesis much more efficiently than most plants on Earth. Their goal is to insert its genes into the iconic lab organism E. coli, turning it from a bacterium that cannot make its own food into one that can, as reported in Metabolic Engineering. Succeeding means E. coli could become an efficient photosynthetic "engine" to generate new biofuels and other sustainable products. More...
A research team that includes Wyss Core Faculty member Peng Yin and Postdoctoral Fellows Wei Sun and Yonggang Ke has built templates made of folded DNA nanostructures, which they used to create precise shapes made of graphene. The new fabrication strategy, pioneered by Yin, could help researchers design and build electronic circuits components. Graphene is a light substance made of pure carbon that has ideal electronic properties for integrated circuits but has thus far been difficult to work with and produce. More...
DNA nanotubes: New lens into proteins
A team led by Wyss Core Faculty member William Shih has developed a new method that could help take biological imaging to the next level, as reported recently in Nature Protocols. The technique uses "DNA origami," a method Shih has pioneered, to create DNA nanotubes -- which are assembled into dilute liquid crystals that can be specifically used to study integral membrane proteins (IMPs) using solution nuclear magnetic resonance (NMR) spectroscopy. IMPs can be seen as gateways to the cell (IMP mutations are at the core of various diseases, for example), but they have been difficult for researchers to study using traditional NMR techniques.
Clinging to crevices
A team of scientists including Wyss Core Faculty member Joanna Aizenberg and Wyss Staff Scientist Philsoek Kim found that the flagella of the bacterium Escherichia coli act like biological grappling hooks, reaching far into nanoscale crevices and latching the bacteria in place -- even on rough surfaces and those designed to resist water. A scourge of the healthcare industry, bacteria like E. coli are adept at clinging to the materials used in medical implants like pacemakers, prosthetics, stents, and catheters, causing dangerous infections. The findings, published in the Proceedings of the National Academy of Sciences (PNAS), suggest that antibacterial materials should incorporate both structural and chemical deterrents to bacterial attachment.
MAGE animation: Narrated by George Church
Multiplex Automated Genome Engineering, MAGE, is a cutting-edge technology that can accelerate and direct evolution within a population of cells -- sort of like natural selection in "fast forward" mode. In this new animation, Core Faculty member George Church explains MAGE's elegant "modus operandi," including what it means for the future of genetic engineering. More...
Inspiration from the bastard hogberry
A team at Harvard University, supported in part by the Wyss Institute, and the University of Exeter, UK, has invented a new fiber that changes color when stretched. Inspired by the fruit of the plant known as "bastard hogberry," the researchers engineered unique structures that re-create the fruit's striking blue-green hue. When combined with elastic material, these structures could lend themselves to the creation of smart fabrics that visibly react to heat or pressure, as described in Advanced Materials. More...
Bacteria inspire new genome engineering tool
A team led by Core Faculty member George Church has created an RNA-guided editing tool that allows researchers to integrate DNA changes into the genomes of living cells, faster and easier than ever before. Their inspiration came from the Cas9 enzyme system in the bacterial immune system, which uses short strands of RNA to target and cut invading viral DNA. The work, reported in Science, could one day enable engineering of multiple changes in different genes and then testing them simultaneously to see what role they play in complex diseases. More...
Leaping lizards ... or 3-legged soft robots
A team of scientists led by Core Faculty member George Whitesides is gearing up soft robots that might one day be used in search and rescue missions. Their latest achievement was triggering a three-legged soft robot to jump more than 30 times its own height by igniting methane -- an explosive chemical reaction -- in tubes connected to the robotic legs, as reported in Angewandte Chemie. What's more, the robot landed on its own "feet." Jumping, a movement previously only demonstrated for hard systems, would be an important skill for a soft robot navigating challenging terrain.
Shaping the beat of your heart
Scientists have postulated for more than 20 years that there is a connection between the shape of the heart and its contractile function, particularly in response to various physiological (e.g., exercise) and pathological conditions (e.g., heart disease). While has been understood that heart cells generally elongate in a failing heart, for example, the intricacies of how this happens at a structural level have remained unclear. An interdisciplinary team led by Core Faculty member Kit Parker shed light on this mystery in a study published in The American Journal of Pathology. Their data suggest that the shape of cardiomyocytes (cells that comprise the heart muscle) is critical in determining their ability to contract; their shape regulates their intracellular structure and influences their ability to metabolize calcium.
Injectable sponges to deliver drugs and cells
A team of bioengineers led by Wyss Core Faculty member David J. Mooney, has developed a gel-based sponge that can be molded to any shape, loaded with drugs or stem cells, compressed, and delivered via injection. As reported in the Proceedings of the National Academy of Sciences, it pops back to its original shape and gradually releases its cargo once inside the body before safely degrading. More...
DNA barcode: Scanning the future of bioimaging
Much like checkout clerks use machines that scan barcodes to identify what customers are buying, scientists use microscopes and their own kinds of barcodes to help them identify parts of a cell or types of molecules. But their barcodes only come in a handful of "styles," limiting what they can study at one time -- until now. Three Wyss Core Faculty members, Peng Yin, William Shih, George Church, and team, have created a new barcode with the potential to help them gather vastly more vital information, at one time, than ever before. The results were reported in Nature Chemistry. More...
Getting a grip on tentacles
Wyss Core Faculty member George Whitesides leads a team of researchers that is developing soft robots that can perform complex motions and tasks, even in the most confined and hazardous spaces, and at low cost. Inspired by the flexibility and dexterity of biological muscular systems such as the trunk of an elephant and the octopus arm, the team’s latest study, in Advanced Materials, describes the novel design and fabrication of soft robotic tentacles that can move in three dimensions and grip complex objects such as a flower or horse-shoe-shaped object. The design does not yet allow for any kind of heavy lifting, but the method is simple, fast, and relatively inexpensive.
Toward building more robust protein textiles
A team led by Wyss Core Faculty member Kevin "Kit" Parker has developed models to further characterize biomimetic textiles composed of fibronectin proteins. These textiles could be used as scaffoldings to promote wound healing and to grow organs. The team studied how the material responds to mechanical loading and showed that these fabrics can extend up to nine times their original length without breaking. They reported their results in Nano Letters.
Under the leadership of Wyss Core Faculty member Rob Wood, a team of scientists and engineers is developing biologically inspired robots that can fly and hold tremendous potential value for search and rescue missions, hazardous environmental explorations, and mass pollination. Wood -- in collaboration with Wyss Staff Mechanical Engineer Kevin Galloway and lead author Ranjara Sahai, a postdoctoral researcher at Harvard's Microrobotics Laboratory -- describes in IEEE Transactions on Robotics a new design for the flapping wings of micro air vehicles. The novel approach achieves power and weight savings and a more integrated design.
Soft robotic devices: Breaking down barriers
The design of a bio-inspired soft robotic assistive device to help brain-injured children move more effectively is showcased in a new article in Ecological Psychology. The paper, which describes how biologically inspired design overlaps with principles of ecological science such as multifunctionality and modularity, is presented by a large, multidisciplinary team at the Wyss Institute, Draper Laboratory, MIT, and Boston University and includes Core Faculty members Radhika Nagpal, Conor Walsh, and Rob Wood; Associate Faculty member Eugene Goldfield; Senior Staff Engineer Leia Stirling; Staff Research Scientist Damian Kelty-Stephen; Technology Development Fellows Yong-Lae Park and Diana Young; and Postdoctoral Fellows Bor-Rong Chen and Michael Wehner.
Helping clot busters reach their target
Wyss Institute Founding Director Don Ingber, Technology Development Fellow Netanel Korin, and an inter-disciplinary and inter-institutional team reported in Science their development of a nanodevice that delivers clot-busting drugs directly to obstructed blood vessels, dissolving blood clots before they cause serious damage or even death. The novel nanotherapeutic has shown improved survival in mice using a small fraction of the normal therapeutic dose, which should translate into fewer side effects, such as bleeding, and greater safety over current treatments. More...
Smarter "smart" materials
A team led by Core Faculty member Joanna Aizenberg describe in Nature how they created materials that can self-regulate in response to environmental change. Called SMARTS (Self-regulated Mechano-chemical Adaptively Reconfigurable Tunable System), the system can, in principle, be tailored to maintain a set acidity, pressure, or just about any other desired parameter by meeting the environmental changes with a compensatory chemical feedback response. More...
An artificial jellyfish that "swims"
Combining recent advances in marine biomechanics, materials science, and tissue engineering, a team of researchers led by Core Faculty member Kit Parker has turned inanimate silicone and living cardiac muscle cells into a freely swimming "jellyfish." Their article describing the engineered jellyfish in Nature Biotechnology provides proof of concept for reverse engineering a variety of muscular organs and simple life forms. More...
Another success for SLIPS
SLIPS holds the promise of preventing a wide range of liquids from sticking to almost any surface. With their latest findings, published in the Proceedings of the National Academy of Sciences, Wyss Core Faculty member Joanna Aizenberg, graduate student Alexander Epstein, and Postdoctoral Fellow Tak-Sing Wong have developed a slick way to prevent bacterial communities from ever forming into biofilms, which stick to everything from copper pipes and ship hulls to glass catheters and human teeth. More...
Surviving extreme dehydration
Most organisms die without water. But a bacterial spore has the remarkable ability to survive long periods of drought intact. Wyss Core faculty member L. Mahadevan and Wyss Collaborator Ozgur Sahin believe this extraordinary characteristic lies in the shifting folds of a bacterium's wrinkled coat. This research can form the basis for developing new, flexible materials that dynamically adapt to changes in their environment while providing the strength to withstand extensive physical stresses. More...
Unlocking the secrets of circulating tumor cells
The important patient-specific information embedded in rare circulating tumor cells has been difficult to access, but a new microdevice created by researchers at the Wyss and Children's Hospital Boston could change that. The new technology, described in Lab on a Chip, has the potential to be a valuable tool for cancer diagnosis and treatment. Don Ingber and Postdoctoral Fellow Joo Kang led the research team. More...
Want to walk a tightrope? Do the math.
It may seem obvious that tightrope walkers need good balance, but a study coauthored by Core Faculty Member L. Mahadevan has found that for these high-wire walkers, good "balance" doesn't only refer to weight distribution. It also means the ability to balance the complex challenges of perception and motor control. In a recent article in the Journal of the Royal Society Interface, he offers a mathematical explanation for how these athletes remain upright. Such calculations could help scientists better understand how the brain and body work together to pull off difficult tasks.
The Tell-Tale Heart
A team lead by Core Faculty Member Kit Parker and former Postdoctoral Fellow Anna Grosberg has developed a range of devices to help measure smooth and striated muscle contractility. Accurate contractility data can aid in the development of more effective and safe treatments for cardiovascular disease. The device is based on muscular thin film technology in which an elastic film is lined with engineered muscle cells to simulate the heart's or vessel's contractile strength. Their findings appeared in the Journal of Pharmacological and Toxicological Methods.
Lessons from the mighty mantis shrimp
The club-like appendages of the peacock mantis shrimp are strong enough to smash open its daily diet of mollusks and crustaceans. In studying these extraordinary features, Wyss research associate James Weaver and colleagues found that the toughness results from a unique composite structure that helps disperse the force of the impact and prevent cracks from spreading. Their findings, which were just published in Science, could provide insights into the fabrication of tough new hybrid materials.
Genetic switchboard could program bacteria
Wyss Core faculty member James Collins and colleagues have developed a genetic switchboard that controls and links multiple biological circuits and pathways, much as an electronic circuit board controls and links electronic components and pathways. And just as the latter is used to program the behavior of a computer, so can the new tool be used to program the behavior of an organism. Such an advanced tool has enormous potential for programming bacteria to produce sugar, biofuels, and drugs. Their findings appear in the Proceedings of the National Academy of Sciences.
Robotic insects spring to life
A new technique inspired by pop-up books and origami will someday allow rapid fabrication of clones of microrobots or virtually any other type of electromechanical device to be mass-produced by the sheet. The ingenious layering and folding process was devised by doctoral candidates Pratheev Sreetharan, J. Peter Whitney, and Wyss Core Faculty member Rob Wood, enables the rapid fabrication of microrobots and a broad range of electromechanical devices. The Monolithic Bee (shown here) is a robotic insect approximately the size of a U.S. quarter which pops up within a scaffold that performs more than 20 origami assembly folds. More...
A speedier approach to genetic engineering
In a new article in Nature Methods, Technology Development Fellow Harris Wang and Core Faculty member George Church describe further advances in multiplex automated genome engineering (MAGE). Already one of the most effective ways of genetically changing a bacterium to, for example, produce drugs or biofuels, MAGE is limited to using short strands of DNA -- typically a few bases. The latest method can handle 20 bases at a time, making the process significantly faster.
Magnetic fields are everywhere, but few organisms can sense them. Now, Keiji Nishida from Harvard Medical School and Wyss Core Faculty member Pam Silver have developed a method for inducing magnetic sensitivity in an organism that is not naturally magnetic -- yeast. The technology could potentially be used to magnetize a variety of different cell types so that they can be targeted, removed, isolated, or even traced in a number of industrial and medical settings. More...
Sweet new advance
A recent publication in Applied and Environmental Microbiology highlights a significant new advance in a Wyss program to coax bacteria into producing sugar. Core Faculty Member Pam Silver, Advanced Technology Team member Jeff Way, and Postdoctoral Fellow Daniel Ducat have engineered a strain of cyanobacteria to be 100-fold more efficient than previous approaches used in microbes to convert light and CO2 into sucrose. The new technology, which could one day help meet the huge industrial demand for sugar (as a feedstock for producing chemicals and fuels), offers a key advantage over current sources of sugar, such as corn and sugarcane. While these traditional crops require large swaths of prime agricultural land, the engineered microbes can be productive in even the most barren landscapes. Moreover, if brought to scale, research suggests they might outproduce the food crops.
Probing DNA with unprecedented accuracy
Wyss Postdoctoral Fellow David Zhang and Wyss Core Faculty Member Peng Yin have developed a highly accurate molecular probe for identifying specific DNA and RNA sequences under a wide range of operating conditions. By improving the reliability of biomedical devices, such as microarray analysis and disease marker detection, the method could lead to powerful new tools for basic research and clinical diagnostics. Zhang and Yin's findings appeared in the online edition of Nature Chemistry. More...
Developing accurate methods for testing the toxicity and efficacy of cardiovascular drugs has been hampered by the difficulty of replicating both the contractility of heart tissue and its electrical activity in an in vitro model. But now a team led by Wyss Core Faculty Member Kit Parker and Wyss postdoctoral fellow Anna Grosberg has designed a heart-on-a-chip device that uses novel muscular thin-film technology to more accurately replicate these functions. Their findings, which could ultimately lead to more effective cardiovascular treatments, appear as the cover story in a recent issue of Lab on a Chip.
Tools developed to re-program bacteria
Photosynthetic bacteria rely on complex protein structures to house the enzymes required to fix carbon. Wyss Core Faculty Member Pam Silver and colleagues recently showed that these elaborate pathways can be produced in bacteria that do not normally fix carbon. Their work, the findings for which appear in the Proceedings of the National Academy of Sciences, is a significant step toward developing genetic tools that can program bacteria to perform useful functions, such as produce biofuels.
New hope for cardiac repair
A research team that includes Wyss Associate Faculty Member Ali Khademhosseini has developed a surface coating that may one day help repair cardiovascular injuries. Based on a hydrogel, the coating could be used on artificial cardiovascular implants to attract and capture the cells needed to induce regeneration. The research findings were recently published in the Journal of Tissue Engineering and Regenerative Medicine.
New "shrilk" material could replace plastic
Taking inspiration from insect cuticle, Javier Fernandez and Don Ingber have developed a new low-cost, biodegradable material that has exceptional strength and toughness. Called "Shrilk" because its components come from shrimp and silk, the material could one day replace plastic in trash bags and packaging or be used to suture load-bearing wounds or as scaffolding for tissue regeneration. Shrilk is described in a recent article in Advanced Materials. More...
Walk like a starfish
Inspired by squid and starfish, a new soft robot can crawl, undulate, and squeeze under obstacles, as described in PNAS and as shown in a report by the BBC. The robot was built by a team led by George Whitesides. Soft robots are more resistant to damage from real-world hazards than rigid designs.
Unlocking secrets of a columbine
New research involving L. Mahadevan helps explain how a columbine flower is able to tailor the length of its nectar spurs to attract specific pollinators. According to results published in the Proceedings of the Royal Society, the differences in length result from subtle differences in the extent of cell elongation. More...
Fine tuning surface structure at the nano scale
In a recent paper in Physical Review Letters, Joanna Aizenberg and colleagues describe a new way to make a variety of complex patterned surfaces by self-assembly. The method, which they call meniscus lithography, involves a dynamic feedback process that occurs when nanopillars assemble in an evaporating liquid. Their findings offer a simple way to fine-tune surfaces for a variety of sensing, adhesive, and controlled wetting applications.
Shining light on quantum networks
A research team that includes Wyss Staff Scientist Mughees Khan has reached a milestone on the road to quantum networks in which information is carried through a network via light. The team managed to capture light in tiny diamond pillars and then release a stream of single photons at a controllable rate. The findings appeared in an October issue of Nature Photonics.
Organ building: The whole tooth
After determining that mechanical forces play a critical role in organ formation, researchers from the Wyss and Children's Hospital Boston were able to induce formation of a whole tooth in the lab. Their findings, which appeared in Developmental Cell, could lead to a new approach for organ engineering in humans.
New collaboration to create resilient fibers
Neel Joshi's and Kit Parker's teams have joined forces to create mechanically reinforced composite fibers for medical applications. These resilient fibers could be used to make implantable devices that can withstand the mechanical stresses in the human body. Funding of $50k will be provided by Harvard's Materials Research Science and Engineering Center.
Hijacking the genetic code using directed evolution
Scientists have copied an entire genome before, but now, in what the New York Times says may be an even more significant advance, a research team that includes George Church and Harris Wang has been able to radically change a genome by performing large-scale, simultaneous "edits." Their findings appeared in a July issue of Science.
Communicating secret messages with W-ink
Joanna Aizenberg, Ian Burgess, and Ben Hatton were part of the team that invented "watermark ink," a strip of material that can instantly identify unknown liquids by their surface tension. The strip, which fits in the palm of a hand and doesn't need a power source, might be used to identify the specific toxins in a chemical spill. Watermark ink was described in Proceedings of the National Academy of Sciences and covered by Scientific American, Popular Mechanics, and Discover magazine.
Turning a cell into a factory
In what could be a significant step toward converting cells into tiny biological production facilities, a team led by Faisal Aldaye and core faculty member Pamela Silver has developed a novel technology for controlling the behavior of a cell, in much the same way that an integrated circuit directs the behavior of a computer or cell phone. Their new approach, the findings for which appeared in Science, uses the nucleic acid, RNA, as a building block for a tool that programs a cell to do useful things, such as produce biofuels or drugs. More...
Explaining the looping pattern of the intestine
Between conception and birth, the human gut grows more than two meters long, coiling inside the abdomen. Within a given species, the developing gut always loops in the same formation -- but, until now, it has not been clear why. Using mathematics and computer science, a group of researchers that includes Wyss core faculty member L. Mahadevan discovered that the looping pattern results from a balance of forces between the gut tube and neighboring tissues. Their interdisciplinary research findings were published in the August 4 issue of Nature.
Bioengineer/soldier attacks brain trauma
Kit Parker has identified the cellular mechanism that translates mechanical forces into subtle, yet disastrous, physiological changes in the brain during a traumatic injury. His findings, which appeared over the summer in both the Proceedings of the National Academy of Sciences and PLoS One, offer urgently needed direction for research in treating soldiers who are sustaining these types of injuries. Parker's work received significant media coverage around the world, including a CNN segment.
DNA nanotechnology grows up
William Shih lent his perspective to an article in Science entitled "DNA Nanotechnology Grows Up." The piece chronicled the rate of acceptance of DNA nanotechnology -- in which DNA building blocks assemble themselves into different structures--as a tool for serious research.