Tag Archives: Tufts University

AI assistant makes scientific discovery at Tufts University (US)

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In light of this latest research from Tufts University, I thought it might be interesting to review the “algorithms, artificial intelligence (AI), robots, and world of work” situation before moving on to Tufts’ latest science discovery. My Feb. 5, 2015 post provides a roundup of sorts regarding work and automation. For those who’d like the latest, there’s a May 29, 2015 article by Sophie Weiner for Fast Company, featuring a predictive interactive tool designed by NPR (US National Public Radio) based on data from Oxford University researchers, which tells you how likely automating your job could be, no one knows for sure, (Note: A link has been removed),

Paralegals and food service workers: the robots are coming.

So suggests this interactive visualization by NPR. The bare-bones graphic lets you select a profession, from tellers and lawyers to psychologists and authors, to determine who is most at risk of losing their jobs in the coming robot revolution. From there, it spits out a percentage. …

You can find the interactive NPR tool here. I checked out the scientist category (in descending order of danger: Historians [43.9%], Economists, Geographers, Survey Researchers, Epidemiologists, Chemists, Animal Scientists, Sociologists, Astronomers, Social Scientists, Political Scientists, Materials Scientists, Conservation Scientists, and Microbiologists [1.2%]) none of whom seem to be in imminent danger if you consider that bookkeepers are rated at  97.6%.

Here at last is the news from Tufts (from a June 4, 2015 Tufts University news release, also on EurekAlert),

An artificial intelligence system has for the first time reverse-engineered the regeneration mechanism of planaria–the small worms whose extraordinary power to regrow body parts has made them a research model in human regenerative medicine.

The discovery by Tufts University biologists presents the first model of regeneration discovered by a non-human intelligence and the first comprehensive model of planarian regeneration, which had eluded human scientists for over 100 years. The work, published in PLOS Computational Biology, demonstrates how “robot science” can help human scientists in the future.

To mine the fast-growing mountain of published experimental data in regeneration and developmental biology Lobo and Levin developed an algorithm that would use evolutionary computation to produce regulatory networks able to “evolve” to accurately predict the results of published laboratory experiments that the researchers entered into a database.

“Our goal was to identify a regulatory network that could be executed in every cell in a virtual worm so that the head-tail patterning outcomes of simulated experiments would match the published data,” Lobo said.

The paper represents a successful application of the growing field of “robot science” – which Levin says can help human researchers by doing much more than crunch enormous datasets quickly.

“While the artificial intelligence in this project did have to do a whole lot of computations, the outcome is a theory of what the worm is doing, and coming up with theories of what’s going on in nature is pretty much the most creative, intuitive aspect of the scientist’s job,” Levin said. “One of the most remarkable aspects of the project was that the model it found was not a hopelessly-tangled network that no human could actually understand, but a reasonably simple model that people can readily comprehend. All this suggests to me that artificial intelligence can help with every aspect of science, not only data mining but also inference of meaning of the data.”

Here’s a link to and a citation for the paper,

Inferring Regulatory Networks from Experimental Morphological Phenotypes: A Computational Method Reverse-Engineers Planarian Regeneration by Daniel Lobo and Michael Levin. PLOS (Computational Biology) DOI: DOI: 10.1371/journal.pcbi.1004295 Published: June 4, 2015

This paper is open access.

It will be interesting to see if attributing the discovery to an algorithm sets off criticism suggesting that the researchers overstated the role the AI assistant played.

Synthesizing spider silk

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Most of the research on spider silk and spider webs that’s featured here is usually from the Massachusetts Institute of Technology (MIT) and, more specifically, from professor Markus J. Buehler. This May 28, 2015 news item on ScienceDaily, which heralds the development of synthetic spider silk, is no exception,

After years of research decoding the complex structure and production of spider silk, researchers have now succeeded in producing samples of this exceptionally strong and resilient material in the laboratory. The new development could lead to a variety of biomedical materials — from sutures to scaffolding for organ replacements — made from synthesized silk with properties specifically tuned for their intended uses.

The findings are published this week in the journal Nature Communications by MIT professor of civil and environmental engineering (CEE) Markus Buehler, postdocs Shangchao Lin and Seunghwa Ryu, and others at MIT, Tufts University, Boston University, and in Germany, Italy, and the U.K.

The research, which involved a combination of simulations and experiments, paves the way for “creating new fibers with improved characteristics” beyond those of natural silk, says Buehler, who is also the department head in CEE. The work, he says, should make it possible to design fibers with specific characteristics of strength, elasticity, and toughness.

The new synthetic fibers’ proteins — the basic building blocks of the material — were created by genetically modifying bacteria to make the proteins normally produced by spiders. These proteins were then extruded through microfluidic channels designed to mimic the effect of an organ, called a spinneret, that spiders use to produce natural silk fibers.

A May 28, 2015 MIT news release (also on EurekAlert), which originated the news item, describes the work in more detail,

While spider silk has long been recognized as among the strongest known materials, spiders cannot practically be bred to produce harvestable fibers — so this new approach to producing a synthetic, yet spider-like, silk could make such strong and flexible fibers available for biomedical applications. By their nature, spider silks are fully biocompatible and can be used in the body without risk of adverse reactions; they are ultimately simply absorbed by the body.

The researchers’ “spinning” process, in which the constituent proteins dissolved in water are extruded through a tiny opening at a controlled rate, causes the molecules to line up in a way that produces strong fibers. The molecules themselves are a mixture of hydrophobic and hydrophilic compounds, blended so as to naturally align to form fibers much stronger than their constituent parts. “When you spin it, you create very strong bonds in one direction,” Buehler says.

The team found that getting the blend of proteins right was crucial. “We found out that when there was a high proportion of hydrophobic proteins, it would not spin any fibers, it would just make an ugly mass,” says Ryu, who worked on the project as a postdoc at MIT and is now an assistant professor at the Korea Advanced Institute of Science and Technology. “We had to find the right mix” in order to produce strong fibers, he says.

The researchers made use of computational modelling to speed up the process of synthesizing proteins for synthetic spider silk, from the news release,

This project represents the first use of simulations to understand silk production at the molecular level. “Simulation is critical,” Buehler explains: Actually synthesizing a protein can take several months; if that protein doesn’t turn out to have exactly the right properties, the process would have to start all over.

Using simulations makes it possible to “scan through a large range of proteins until we see changes in the fiber stiffness,” and then home in on those compounds, says Lin, who worked on the project as a postdoc at MIT and is now an assistant professor at Florida State University.

Controlling the properties directly could ultimately make it possible to create fibers that are even stronger than natural ones, because engineers can choose characteristics for a particular use. For example, while spiders may need elasticity so their webs can capture insects without breaking, those designing fibers for use as surgical sutures would need more strength and less stretchiness. “Silk doesn’t give us that choice,” Buehler says.

The processing of the material can be done at room temperature using water-based solutions, so scaling up manufacturing should be relatively easy, team members say. So far, the fibers they have made in the lab are not as strong as natural spider silk, but now that the basic process has been established, it should be possible to fine-tune the materials and improve its strength, they say.

“Our goal is to improve the strength, elasticity, and toughness of artificially spun fibers by borrowing bright ideas from nature,” Lin says. This study could inspire the development of new synthetic fibers — or any materials requiring enhanced properties, such as in electrical and thermal transport, in a certain direction.

Here’s a link to and a citation for the paper,

Predictive modelling-based design and experiments for synthesis and spinning of bioinspired silk fibres by Shangchao Lin, Seunghwa Ryu, Olena Tokareva, Greta Gronau, Matthew M. Jacobsen, Wenwen Huang, Daniel J. Rizzo, David Li, Cristian Staii, Nicola M. Pugno, Joyce Y. Wong, David L. Kaplan, & Markus J. Buehler. Nature Communications 6, Article number: 6892 doi:10.1038/ncomms7892 Published 28 May 2015

This paper is behind a paywall.

My two most recent (before this one) postings about Buehler’s work are an August 5, 2014 piece about structural failures and a June 4, 2014 piece about spiderwebs and music.

Finally, I recognized one of the authors, Nicola Pugno from Italy. He’s been mentioned here more than once in regard to his biomimicry work which has often been focused on geckos and their adhesive qualities as per this April 3, 2014 post announcing his book ‘An Experimental Study on Adhesive or Anti-Adhesive, Bio-Inspired Experimental Nanomaterials‘ (co-authored with Emiliano Lepore).

Producing stronger silk musically

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Markus Buehler and his interdisciplinary team (my previous posts on their work includes Gossamer silk that withstands hurricane force winds and Music, math, and spiderwebs) have synthesized a new material based on spider silk. From the Nov. 28, 2012 news item on ScienceDaily,

Pound for pound, spider silk is one of the strongest materials known: Research by MIT’s [Massachusetts Institute of Technology] Markus Buehler has helped explain that this strength arises from silk’s unusual hierarchical arrangement of protein building blocks.

Now Buehler — together with David Kaplan of Tufts University and Joyce Wong of Boston University — has synthesized new variants on silk’s natural structure, and found a method for making further improvements in the synthetic material.

And an ear for music, it turns out, might be a key to making those structural improvements.

Here’s Buehler describing the work in an MIT video clip,

The Nov. 28, 2012 MIT news release by David Chandler provides more details,

Buehler’s previous research has determined that fibers with a particular structure — highly ordered, layered protein structures alternating with densely packed, tangled clumps of proteins (ABABAB) — help to give silk its exceptional properties. For this initial attempt at synthesizing a new material, the team chose to look instead at patterns in which one of the structures occurred in triplets (AAAB and BBBA).

Making such structures is no simple task. Kaplan, a chemical and biomedical engineer, modified silk-producing genes to produce these new sequences of proteins. Then Wong, a bioengineer and materials scientist, created a microfluidic device that mimicked the spider’s silk-spinning organ, which is called a spinneret.

Even after the detailed computer modeling that went into it, the outcome came as a bit of a surprise, Buehler says. One of the new materials produced very strong protein molecules — but these did not stick together as a thread. The other produced weaker protein molecules that adhered well and formed a good thread. “This taught us that it’s not sufficient to consider the properties of the protein molecules alone,” he says. “Rather, [one must] think about how they can combine to form a well-connected network at a larger scale.”
…

The different levels of silk’s structure, Buehler says, are analogous to the hierarchical elements that make up a musical composition — including pitch, range, dynamics and tempo. The team enlisted the help of composer John McDonald, a professor of music at Tufts, and MIT postdoc David Spivak, a mathematician who specializes in a field called category theory. Together, using analytical tools derived from category theory to describe the protein structures, the team figured out how to translate the details of the artificial silk’s structure into musical compositions.

The differences were quite distinct: The strong but useless protein molecules translated into music that was aggressive and harsh, Buehler says, while the ones that formed usable fibers sound much softer and more fluid.
…

Combining materials modeling with mathematical and musical tools, Buehler says, could provide a much faster way of designing new biosynthesized materials, replacing the trial-and-error approach that prevails today. Genetically engineering organisms to produce materials is a long, painstaking process, he says, but this work “has taught us a new approach, a fundamental lesson” in combining experiment, theory and simulation to speed up the discovery process.

Materials produced this way — which can be done under environmentally benign, room-temperature conditions — could lead to new building blocks for tissue engineering or other uses, Buehler says: scaffolds for replacement organs, skin, blood vessels, or even new materials for use in civil engineering.
…
It may be that the complex structures of music can reveal the underlying complex structures of biomaterials found in nature, Buehler says. “There might be an underlying structural expression in music that tells us more about the proteins that make up our bodies. After all, our organs — including the brain — are made from these building blocks, and humans’ expression of music may inadvertently include more information that we are aware of.”

“Nobody has tapped into this,” he says, adding that with the breadth of his multidisciplinary team, “We could do this — making better bio-inspired materials by using music, and using music to better understand biology.”

At the end of Chandler’s news release there’s a notice about a summer course with Markus Buehler,

For those interested in the work Professor Buehler is doing, you may also be interested to know that he is offering a short course on campus this summer called Materials By Design.

Materials By Design
June 17-20, 2013
shortprograms.mit.edu/mbd

Through lectures and hands-on labs, participants will learn how materials failure, studied from a first principles perspective, can be applied in an effective “learning-from-failure approach” to design and make novel materials. Participants will also learn how superior material properties in nature and biology can be mimicked in bioinspired materials for applications in new technology. This course will be of interest to scientists, engineers, managers, and policy makers working in the area of materials design, development, manufacturing, and testing. [emphasis mine]

I wasn’t expecting to see managers and policy makers as possible students for this course.

By the way, Buehler is not the only scientist to make a connection between music and biology (although he seems to be the only person using the concept for applications), there’s also geneticist and biophysicist, Mae Wan Ho and her notion of quantum jazz. From the Quantum Jazz Biology* article by David Reilly in the June 23, 2010 Isis Report,

I use the analogy of ‘quantum jazz’ to express the quantum coherence of the organism. It goes through a fantastic range of space and time scales, from the tiniest atom or subatomic particle to the whole organism and beyond. Organisms communicate with other organisms, and are attuned to natural rhythms, so they have circadian rhythms, annual rhythms, and so on. At the other extreme, you have very fast reactions that take place in femtoseconds. And all these rhythms are coordinated, there is evidence for that.

Tooth tattoos at Tufts University

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In spring 2012, there was a fluttering in the blogosphere about tooth tattoos with the potential for monitoring dental health. As sometimes happens, I put off posting about the work until it seemed everyone else had written about it (e.g. Mar. 30, 2012 posting by Dexter Johnson for his Nanoclast blog on the IEEE website) and there was nothing left for me to say.  Happily, the researchers at Tufts University (where part of this research [Princeton University is also involved] is being pursued) have released more information in a Nov. 1, 2012 news article by David Levin,

The sensor, dubbed a “tooth tattoo,” was developed by the Princeton nanoscientist Michael McAlpine and Tufts bioengineers Fiorenzo Omenetto, David Kaplan and Hu Tao. The team first published their research last spring in the journal Nature Communications.

The sensor is relatively simple in its construction, says McAlpine. It’s made up of just three layers: a sheet of thin gold foil electrodes, an atom-thick layer of graphite known as graphene and a layer of specially engineered peptides, chemical structures that “sense” bacteria by binding to parts of their cell membranes.

“We created a new type of peptide that can serve as an intermediary between bacteria and the sensor,” says McAlpine. “At one end is a molecule that can bond with the graphene, and at the other is a molecule that bonds with bacteria,” allowing the sensor to register the presence of bacteria, he says.

Because the layers of the device are so thin and fragile, they need to be mounted atop a tough but flexible backing in order to transfer them to a tooth. The ideal foundation, McAlpine says, turns out to be silk—a substance with which Kaplan and Omenetto have been working for years.

By manipulating the proteins that make up a single strand of silk, it’s possible to create silk structures in just about any shape, says Omenetto, a professor of biomedical engineering at Tufts. Since 2005, he’s created dozens of different structures out of silk, from optical lenses to orthopedic implants. Silk is “kind of like plastic, in that we can make [it] do almost anything,” he says. “We have a lot of control over the material. It can be rigid. It can be flexible. We can make it dissolve in water, stay solid, become a gel—whatever we need.”

Omenetto, Kaplan and Tao created a thin, water-soluble silk backing for McAlpine’s bacterial sensor—a film that’s strong enough to hold the sensor components in place, but soft and pliable enough to wrap easily around the irregular contours of a tooth.

To apply the sensor, McAlpine says, you need only to wet the surface of the entire assembly—silk, sensor and all—and then press it onto the tooth. Once there, the silk backing will dissolve within 15 or 20 minutes, leaving behind the sensor, a rectangle of interwoven gold and black electrodes about half the size of a postage stamp and about as thick as a sheet of paper. The advantage of being attached directly to a tooth means that the sensor is in direct contact with bacteria in the mouth—an ideal way to monitor oral health.

Because the sensor doesn’t carry any onboard batteries, it must be both read and powered simultaneously through a built-in antenna. Using a custom-made handheld device about the size of a TV remote, McAlpine’s team can “ping” that antenna with radio waves, causing it to resonate electronically and send back information that the device then uses to determine if bacteria are present.

The sensor (A), attached to a tooth (B) and activated by radio signals (C), binds with certain bacteria (D). Illustration: Manu Mannoor/Nature Communications (downloaded from http://now.tufts.edu/articles/tooth-tattoo)

In addition to its potential for  monitoring dental health, the tooth tattoo could replace some of the more invasive health monitoring techniques (e.g., drawing blood), from the Tufts University article,

In addition to monitoring oral health, Kugel [Gerard Kugel, Tufts professor of prosthodontics and operative dentistry and associate dean for research at Tufts School of Dental Medicine] believes the tooth tattoo might be useful for monitoring a patient’s overall health. Biological markers for many diseases—from stomach ulcers to AIDS—appear in human saliva, he says. So if a sensor could be modified to react to those markers, it potentially could help dentists identify problems early on and refer patients to a physician before a condition becomes serious.

“The mouth is a window to the rest of the body,” Kugel says. “You can spot a lot of potential health problems through saliva, and it’s a much less invasive way to do diagnostic tests than drawing blood.”

Before monitoring of any type can take place, there is at least one major hurdle still be overcome. Humans are quite sensitive to objects being placed in their mouths. According to one of the researchers, we can sense objects that are 50 to 60 microns wide, about the thickness piece of paper, and that may be too uncomfortable to bear.

H/T Nov. 9, 2012 news item on Nanowerk for pointing me towards the latest information about these tooth tattoos.

Organ chips for DARPA (Defense Advanced Research Projects Agency)

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The Wyss Institute will receive up to  $37M US for a project that integrates ten different organ-on-a-chip projects into one system. From the July 24, 2012 news release on EurekAlert,

With this new DARPA funding, Institute researchers and a multidisciplinary team of collaborators seek to build 10 different human organs-on-chips, to link them together to more closely mimic whole body physiology, and to engineer an automated instrument that will control fluid flow and cell viability while permitting real-time analysis of complex biochemical functions. As an accurate alternative to traditional animal testing models that often fail to predict human responses, this instrumented “human-on-a-chip” will be used to rapidly assess responses to new drug candidates, providing critical information on their safety and efficacy.

…

This unique platform could help ensure that safe and effective therapeutics are identified sooner, and ineffective or toxic ones are rejected early in the development process. As a result, the quality and quantity of new drugs moving successfully through the pipeline and into the clinic may be increased, regulatory decision-making could be better informed, and patient outcomes could be improved.

Jesse Goodman, FDA Chief Scientist and Deputy Commissioner for Science and Public Health, commented that the automated human-on-chip instrument being developed “has the potential to be a better model for determining human adverse responses. FDA looks forward to working with the Wyss Institute in its development of this model that may ultimately be used in therapeutic development.”

Wyss Founding Director, Donald Ingber, M.D., Ph.D., and Wyss Core Faculty member, Kevin Kit Parker, Ph.D., will co-lead this five-year project.

I note that Kevin Kit Parker was mentioned in an earlier posting today (July 26, 2012) titled, Medusa, jellyfish, and tissue engineering, and Donald Ingber in my Dec.1e, 2011 posting about Shrilk and insect skeletons.

As for the Wyss Institute, here’s a description from the news release,

The Wyss Institute for Biologically Inspired Engineering at Harvard University (http://wyss.harvard.edu) uses Nature’s design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world. Working as an alliance among Harvard’s Schools of Medicine, Engineering, and Arts & Sciences, and in partnership with Beth Israel Deaconess Medical Center, Boston Children’s Hospital, Brigham and Women’s Hospital, , Dana Farber Cancer Institute, Massachusetts General Hospital, the University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Tufts University, and Boston University, the Institute crosses disciplinary and institutional barriers to engage in high-risk research that leads to transformative technological breakthroughs. By emulating Nature’s principles for self-organizing and self-regulating, Wyss researchers are developing innovative new engineering solutions for healthcare, energy, architecture, robotics, and manufacturing. These technologies are translated into commercial products and therapies through collaborations with clinical investigators, corporate alliances, and new start-ups.

I hadn’t thought of an organ-on-a-chip as particularly bioinspired so I’ll have to think about that one for a while.

Microneedles from Tufts University

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Here’s some very exciting news from Tufts University in a Dec. 21, 2011 news item on Nanowerk,

Bioengineers at Tufts University School of Engineering have developed a new silk-based microneedle system able to deliver precise amounts of drugs over time and without need for refrigeration. The tiny needles can be fabricated under normal temperature and pressure and from water, so they can be loaded with sensitive biochemical compounds and maintain their activity prior to use. They are also biodegradable and biocompatible.

I have previously written about a micro needle project at the Georgia Institute of Technology in Nov. 9, 2011 posting and about Mark Kendall’s nano vaccine patch on more than one occasion, most recently in my Aug. 3, 2011 posting.

This new drug delivery project surprised me; I didn’t realize that horesradish could also be a drug,

The Tufts researchers successfully demonstrated the ability of the silk microneedles to deliver a large-molecule, enzymatic model drug, horseradish peroxidase (HRP), at controlled rates while maintaining bioactivity. In addition, silk microneedles loaded with tetracycline were found to inhibit the growth of Staphylococcus aureus, demonstrating the potential of the microneedles to prevent local infections while also delivering therapeutics.

“By adjusting the post-processing conditions of the silk protein and varying the drying time of the silk protein, we were able to precisely control the drug release rates in laboratory experiments,” said Fiorenzo Omenetto, Ph.D., senior author on the paper. “The new system addresses long-standing drug delivery challenges, and we believe that the technology could also be applied to other biological storage applications.”

If we’re all lucky, it won’t be too long before syringes are a museum item and we’ll be getting our medication with far less discomfort/pain and, in some cases, fear.