Category Archives: synthetic biology

Some amusements in the time of COVID-19

Gold stars for everyone who recognized the loose paraphrasing of the title, Love in the Time of Cholera, for Gabrial Garcia Marquez’s 1985 novel.

I wrote my headline and first paragraph yesterday and found this in my email box this morning, from a March 25, 2020 University of British Columbia news release, which compares times, diseases, and scares of the past with today’s COVID-19 (Perhaps politicians and others could read this piece and stop using the word ‘unprecedented’ when discussing COVID-19?),

How globalization stoked fear of disease during the Romantic era

In the late 18th and early 19th centuries, the word “communication” had several meanings. People used it to talk about both media and the spread of disease, as we do today, but also to describe transport—via carriages, canals and shipping.

Miranda Burgess, an associate professor in UBC’s English department, is working on a book called Romantic Transport that covers these forms of communication in the Romantic era and invites some interesting comparisons to what the world is going through today.

We spoke with her about the project.

What is your book about?

It’s about global infrastructure at the dawn of globalization—in particular the extension of ocean navigation through man-made inland waterways like canals and ship’s canals. These canals of the late 18th and early 19th century were like today’s airline routes, in that they brought together places that were formerly understood as far apart, and shrunk time because they made it faster to get from one place to another.

This book is about that history, about the fears that ordinary people felt in response to these modernizations, and about the way early 19th-century poets and novelists expressed and responded to those fears.

What connections did those writers make between transportation and disease?

In the 1810s, they don’t have germ theory yet, so there’s all kinds of speculation about how disease happens. Works of tropical medicine, which is rising as a discipline, liken the human body to the surface of the earth. They talk about nerves as canals that convey information from the surface to the depths, and the idea that somehow disease spreads along those pathways.

When the canals were being built, some writers opposed them on the grounds that they could bring “strangers” through the heart of the city, and that standing water would become a breeding ground for disease. Now we worry about people bringing disease on airplanes. It’s very similar to that.

What was the COVID-19 of that time?

Probably epidemic cholera [emphasis mine], from about the 1820s onward. The Quarterly Review, a journal that novelist Walter Scott was involved in editing, ran long articles that sought to trace the map of cholera along rivers from South Asia, to Southeast Asia, across Europe and finally to Britain. And in the way that its spread is described, many of the same fears that people are evincing now about COVID-19 were visible then, like the fear of clothes. Is it in your clothes? Do we have to burn our clothes? People were concerned.

What other comparisons can be drawn between those times and what is going on now?

Now we worry about the internet and “fake news.” In the 19th century, they worried about what William Wordsworth called “the rapid communication of intelligence,” which was the daily newspaper. Not everybody had access to newspapers, but each newspaper was read by multiple families and newspapers were available in taverns and coffee shops. So if you were male and literate, you had access to a newspaper, and quite a lot of women did, too.

Paper was made out of rags—discarded underwear. Because of the French Revolution and Napoleonic Wars that followed, France blockaded Britain’s coast and there was a desperate shortage of rags to make paper, which had formerly come from Europe. And so Britain started to import rags from the Caribbean that had been worn by enslaved people.

Papers of the time are full of descriptions of the high cost of rags, how they’re getting their rags from prisons, from prisoners’ underwear, and fear about the kinds of sweat and germs that would have been harboured in those rags—and also discussions of scarcity, as people stole and hoarded those rags. It rings very well with what the internet is telling us now about a bunch of things around COVID-19.

Plus ça change, n’est-ce pas?

And now for something completely different

Kudos to all who recognized the Monty Python reference. Now, onto the frogfish,

Thank you to the Monterey Bay Aquarium (in California, US).

A March 22, 2020 University of Washington (state) news release features an interview with the author of a new book on frogfishes,

Any old fish can swim. But what fish can walk, scoot, clamber over rocks, change color or pattern and even fight? That would be the frogfish.

The latest book by Ted Pietsch, UW professor emeritus of aquatic and fishery sciences, explores the lives and habits of these unusual marine shorefishes. “Frogfishes: Biodiversity, Zoogeography, and Behavioral Ecology” was published in March [2020] by Johns Hopkins University Press.

Pietsch, who is also curator emeritus of fishes at the Burke Museum of Natural History and Culture, has published over 200 articles and a dozen books on the biology and behavior of marine fishes. He wrote this book with Rachel J. Arnold, a faculty member at Northwest Indian College in Bellingham and its Salish Sea Research Center.

These walking fishes have stepped into the spotlight lately, with interest growing in recent decades. And though these predatory fishes “will almost certainly devour anything else that moves in a home aquarium,” Pietsch writes, “a cadre of frogfish aficionados around the world has grown within the dive community and among aquarists.” In fact, Pietsch said, there are three frogfish public groups on Facebook, with more than 6,000 members.

First, what is a frogfish?

Ted Pietsch: A member of a family of bony fishes, containing 52 species, all of which are highly camouflaged and whose feeding strategy consists of mimicking the immobile, inert, and benign appearance of a sponge or an algae-encrusted rock, while wiggling a highly conspicuous lure to attract prey.

This is a fish that “walks” and “hops” across the sea bottom, and clambers about over rocks and coral like a four-legged terrestrial animal but, at the same time, can jet-propel itself through open water. Some lay their eggs encapsulated in a complex, floating, mucus mass, called an “egg raft,” while some employ elaborate forms of parental care, carrying their eggs around until they hatch.

They are among the most colorful of nature’s productions, existing in nearly every imaginable color and color pattern, with an ability to completely alter their color and pattern in a matter of days or seconds. All these attributes combined make them one of the most intriguing groups of aquatic vertebrates for the aquarist, diver, and underwater photographer as well as the professional zoologist.

I couldn’t resist the ‘frog’ reference and I’m glad since this is a good read with a number of fascinating photographs and illustrations.,

An illustration of the frogfish Antennarius pictus, published by George Shaw in 1794. From a new book by Ted Pietsch, UW professor of emeritus of aquatic and fishery sciences. Courtesy: University of Washington (state)

h/t phys.org March 24, 2020 news item

Building with bacteria

A block of sand particles held together by living cells. Credit: The University of Colorado Boulder College of Engineering and Applied Science

A March 24, 2020 news item on phys.org features the future of building construction as perceived by synthetic biologists,

Buildings are not unlike a human body. They have bones and skin; they breathe. Electrified, they consume energy, regulate temperature and generate waste. Buildings are organisms—albeit inanimate ones.

But what if buildings—walls, roofs, floors, windows—were actually alive—grown, maintained and healed by living materials? Imagine architects using genetic tools that encode the architecture of a building right into the DNA of organisms, which then grow buildings that self-repair, interact with their inhabitants and adapt to the environment.

A March 23, 2020 essay by Wil Srubar (Professor of Architectural Engineering and Materials Science, University of Colorado Boulder), which originated the news item, provides more insight,

Living architecture is moving from the realm of science fiction into the laboratory as interdisciplinary teams of researchers turn living cells into microscopic factories. At the University of Colorado Boulder, I lead the Living Materials Laboratory. Together with collaborators in biochemistry, microbiology, materials science and structural engineering, we use synthetic biology toolkits to engineer bacteria to create useful minerals and polymers and form them into living building blocks that could, one day, bring buildings to life.

In one study published in Scientific Reports, my colleagues and I genetically programmed E. coli to create limestone particles with different shapes, sizes, stiffnesses and toughness. In another study, we showed that E. coli can be genetically programmed to produce styrene – the chemical used to make polystyrene foam, commonly known as Styrofoam.

Green cells for green building

In our most recent work, published in Matter, we used photosynthetic cyanobacteria to help us grow a structural building material – and we kept it alive. Similar to algae, cyanobacteria are green microorganisms found throughout the environment but best known for growing on the walls in your fish tank. Instead of emitting CO2, cyanobacteria use CO2 and sunlight to grow and, in the right conditions, create a biocement, which we used to help us bind sand particles together to make a living brick.

By keeping the cyanobacteria alive, we were able to manufacture building materials exponentially. We took one living brick, split it in half and grew two full bricks from the halves. The two full bricks grew into four, and four grew into eight. Instead of creating one brick at a time, we harnessed the exponential growth of bacteria to grow many bricks at once – demonstrating a brand new method of manufacturing materials.

Researchers have only scratched the surface of the potential of engineered living materials. Other organisms could impart other living functions to material building blocks. For example, different bacteria could produce materials that heal themselves, sense and respond to external stimuli like pressure and temperature, or even light up. If nature can do it, living materials can be engineered to do it, too.

It also take less energy to produce living buildings than standard ones. Making and transporting today’s building materials uses a lot of energy and emits a lot of CO2. For example, limestone is burned to make cement for concrete. Metals and sand are mined and melted to make steel and glass. The manufacture, transport and assembly of building materials account for 11% of global CO2 emissions. Cement production alone accounts for 8%. In contrast, some living materials, like our cyanobacteria bricks, could actually sequester CO2.

The field of engineered living materials is in its infancy, and further research and development is needed to bridge the gap between laboratory research and commercial availability. Challenges include cost, testing, certification and scaling up production. Consumer acceptance is another issue. For example, the construction industry has a negative perception of living organisms. Think mold, mildew, spiders, ants and termites. We’re hoping to shift that perception. Researchers working on living materials also need to address concerns about safety and biocontamination.

The [US] National Science Foundation recently named engineered living materials one of the country’s key research priorities. Synthetic biology and engineered living materials will play a critical role in tackling the challenges humans will face in the 2020s and beyond: climate change, disaster resilience, aging and overburdened infrastructure, and space exploration.

If you have time and interest, this is fascinating. Strubar is a little exuberant and, at this point, I welcome it.

Fitness

The Lithuanians are here for us. Scientists from the Kaunas University of Technology have just published a paper on better exercises for lower back pain in our increasingly sedentary times, from a March 23, 2020 Kaunas University of Technology press release (also on EurekAlert) Note: There are a few minor grammatical issues,

With the significant part of the global population forced to work from home, the occurrence of lower back pain may increase. Lithuanian scientists have devised a spinal stabilisation exercise programme for managing lower back pain for people who perform a sedentary job. After testing the programme with 70 volunteers, the researchers have found that the exercises are not only efficient in diminishing the non-specific lower back pain, but their effect lasts 3 times longer than that of a usual muscle strengthening exercise programme.

According to the World Health Organisation, lower back pain is among the top 10 diseases and injuries that are decreasing the quality of life across the global population. It is estimated that non-specific low back pain is experienced by 60% to 70% of people in industrialised societies. Moreover, it is the leading cause of activity limitation and work absence throughout much of the world. For example, in the United Kingdom, low back pain causes more than 100 million workdays lost per year, in the United States – an estimated 149 million.

Chronic lower back pain, which starts from long-term irritation or nerve injury affects the emotions of the afflicted. Anxiety, bad mood and even depression, also the malfunctioning of the other bodily systems – nausea, tachycardia, elevated arterial blood pressure – are among the conditions, which may be caused by lower back pain.

During the coronavirus disease (COVID-19) outbreak, with a significant part of the global population working from home and not always having a properly designed office space, the occurrence of lower back pain may increase.

“Lower back pain is reaching epidemic proportions. Although it is usually clear what is causing the pain and its chronic nature, people tend to ignore these circumstances and are not willing to change their lifestyle. Lower back pain usually comes away itself, however, the chances of the recurring pain are very high”, says Dr Irina Klizienė, a researcher at Kaunas University of Technology (KTU) Faculty of Social Sciences, Humanities and Arts.

Dr Klizienė, together with colleagues from KTU and from Lithuanian Sports University has designed a set of stabilisation exercises aimed at strengthening the muscles which support the spine at the lower back, i.e. lumbar area. The exercise programme is based on Pilates methodology.

According to Dr Klizienė, the stability of lumbar segments is an essential element of body biomechanics. Previous research evidence shows that in order to avoid the lower back pain it is crucial to strengthen the deep muscles, which are stabilising the lumbar area of the spine. One of these muscles is multifidus muscle.

“Human central nervous system is using several strategies, such as preparing for keeping the posture, preliminary adjustment to the posture, correcting the mistakes of the posture, which need to be rectified by specific stabilising exercises. Our aim was to design a set of exercises for this purpose”, explains Dr Klizienė.

The programme, designed by Dr Klizienė and her colleagues is comprised of static and dynamic exercises, which train the muscle strength and endurance. The static positions are to be held from 6 to 20 seconds; each exercise to be repeated 8 to 16 times.

Caption: The static positions are to be held from 6 to 20 seconds; each exercise to be repeated 8 to 16 times. Credit: KTU

The previous set is a little puzzling but perhaps you’ll find these ones below easier to follow,

Caption: The exercises are aimed at strengthening the muscles which support the spine at the lower back. Credit: KTU

I think more pictures of intervening moves would have been useful. Now. getting back to the press release,

In order to check the efficiency of the programme, 70 female volunteers were randomly enrolled either to the lumbar stabilisation exercise programme or to a usual muscle strengthening exercise programme. Both groups were exercising twice a week for 45 minutes for 20 weeks. During the experiment, ultrasound scanning of the muscles was carried out.

As soon as 4 weeks in lumbar stabilisation programme, it was observed that the cross-section area of the multifidus muscle of the subjects of the stabilisation group has increased; after completing the programme, this increase was statistically significant (p < 0,05). This change was not observed in the strengthening group.

Moreover, although both sets of exercises were efficient in eliminating lower back pain and strengthening the muscles of the lower back area, the effect of stabilisation exercises lasted 3 times longer – 12 weeks after the completion of the stabilisation programme against 4 weeks after the completion of the muscle strengthening programme.

“There are only a handful of studies, which have directly compared the efficiency of stabilisation exercises against other exercises in eliminating lower back pain”, says Dr Klizienė, “however, there are studies proving that after a year, lower back pain returned only to 30% of people who have completed a stabilisation exercise programme, and to 84% of people who haven’t taken these exercises. After three years these proportions are 35% and 75%.”

According to her, research shows that the spine stabilisation exercises are more efficient than medical intervention or usual physical activities in curing the lower back pain and avoiding the recurrence of the symptoms in the future.

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

Effect of different exercise programs on non-specific chronic low back pain and disability in people who perform sedentary work by Saule Sipavicienea, Irina Klizieneb. Clinical Biomechanics March 2020 Volume 73, Pages 17–27 DOI: https://doi.org/10.1016/j.clinbiomech.2019.12.028

This paper is behind a paywall.

Winter jacket made with ‘brewed protein’ and enabled by synthetic biology

It’s called a ‘Moon Parka’,

[downloaded from https://sp.spiber.jp/en/tnfsp/mp/]

Adele Peters in her October 31, 2019 article for Fast Company describes the technology used to make this jacket,

A typical waterproof winter jacket is made with nylon—a material that, like other plastics, is made from petroleum. But a new limited-edition jacket from The North Face Japan uses something called “brewed protein” instead. It’s a material inspired by spider silk that is fermented in giant vats, the same way that breweries make beer.

It’s one of the first uses of a material produced by the Japanese startup Spiber, a company that has spent more than a decade developing a new process to make high-performance textiles and other products that don’t rely on fossil fuels, animals, or natural fibers like cotton, all of which have environmental issues. …

The company designs genes that code for a specific protein—the first was an exact replica of natural spider silk, known for its extreme strength—and then introduces the genes into microorganisms that can produce the protein efficiently. Inside giant tanks, the microorganisms are fed sugar, grow and multiply, and produce the protein through fermentation. …

Spiber first started collaborating with Goldwin, a Japanese outdoor brand that owns the Japanese rights to The North Face, in 2015, and created an early prototype of a jacket then. But it quickly realized that an exact replica of spider silk wouldn’t work well for the application; the material sucks up water, and the jacket needed to be waterproof.

“We spent the last four years going back to the drawing board, redesigning our protein molecule—the very order of the amino acids in the molecule,” says Meyer [Daniel Meyer, Spiber’s head of corporate global marketing]. “And we created our own hydrophobic [water repellent] version of spider silk. It’s inspired by natural spider silk, but we have made our own design changes such that it would be more hydrophobic and meet the performance requirements of The North Face Japan.”

The jacket is available for purchase but only by a lottery, which has now closed. According to Peters, a large, commercial production facility is being built in Thailand so that at some point a Moon Parka will be affordable. For reference, the lottery jackets were priced at ¥150,000 (about $1,377 US).

You can find Spiber here in mid-March [2020] according to the homepage.

Bionanomotors for bio-inspired robots on the battlefield

An October 9, 2019 news item on ScienceDaily provides some insight into the latest US Army research into robots,

In an effort to make robots more effective and versatile teammates for Soldiers in combat, Army researchers are on a mission to understand the value of the molecular living functionality of muscle, and the fundamental mechanics that would need to be replicated in order to artificially achieve the capabilities arising from the proteins responsible for muscle contraction.

Caption: Army researchers are on a mission to understand the value of the molecular ‘living’ functionality of muscle, and the fundamental mechanics that would need to be replicated in order to artificially achieve the capabilities arising from the proteins responsible for muscle contraction. Credit: US Army-Shutterstock

An October 8, 2019 US Army Research Laboratory news release (also on EurekAlert but published on October 9, 2019), which originated the news item, delves further into the research,

Bionanomotors, like myosins that move along actin networks, are responsible for most methods of motion in all life forms. Thus, the development of artificial nanomotors could be game-changing in the field of robotics research.

Researchers from the U.S. Army Combat Capabilities Development Command’s [CCDC] Army Research Laboratory [ARL] have been looking to identify a design that would allow the artificial nanomotor to take advantage of Brownian motion, the property of particles to agitatedly move simply because they are warm.

The CCDC ARL researchers believe understanding and developing these fundamental mechanics are a necessary foundational step toward making informed decisions on the viability of new directions in robotics involving the blending of synthetic biology, robotics, and dynamics and controls engineering.

“By controlling the stiffness of different geometrical features of a simple lever-arm design, we found that we could use Brownian motion to make the nanomotor more capable of reaching desirable positions for creating linear motion,” said Dean Culver, a researcher in CCDC ARL’s Vehicle Technology Directorate. “This nano-scale feature translates to more energetically efficient actuation at a macro scale, meaning robots that can do more for the warfighter over a longer amount of time.”

According to Culver, the descriptions of protein interactions in muscle contraction are typically fairly high-level. More specifically, rather than describing the forces that act on an individual protein to seek its counterpart, prescribed or empirical rate functions that dictate the conditions under which a binding or a release event occurs have been used by the research community to replicate this biomechanical process.

“These widely accepted muscle contraction models are akin to a black-box understanding of a car engine,” Culver said. “More gas, more power. It weighs this much and takes up this much space. Combustion is involved. But, you can’t design a car engine with that kind of surface-level information. You need to understand how the pistons work, and how finely injection needs to be tuned. That’s a component-level understanding of the engine. We dive into the component-level mechanics of the built-up protein system and show the design and control value of living functionality as well as a clearer understanding of design parameters that would be key to synthetically reproducing such living functionality.”

Culver stated that the capacity for Brownian motion to kick a tethered particle from a disadvantageous elastic position to an advantageous one, in terms of energy production for a molecular motor, has been illustrated by ARL at a component level, a crucial step in the design of artificial nanomotors that offer the same performance capabilities as biological ones.

“This research adds a key piece of the puzzle for fast, versatile robots that can perform autonomous tactical maneuver and reconnaissance functions,” Culver said. “These models will be integral to the design of distributed actuators that are silent, low thermal signature and efficient – features that will make these robots more impactful in the field.”

Culver noted that they are silent because the muscles don’t make a lot of noise when they actuate, especially compared to motors or servos, cold because the amount of heat generation in a muscle is far less than a comparable motor, and efficient because of the advantages of the distributed chemical energy model and potential escape via Brownian motion.

According to Culver, the breadth of applications for actuators inspired by the biomolecular machines in animal muscles is still unknown, but many of the existing application spaces have clear Army applications such as bio-inspired robotics, nanomachines and energy harvesting.

“Fundamental and exploratory research in this area is therefore a wise investment for our future warfighter capabilities,” Culver said.

Moving forward, there are two primary extensions of this research.

“First, we need to better understand how molecules, like the tethered particle discussed in our paper, interact with each other in more complicated environments,” Culver said. “In the paper, we see how a tethered particle can usefully harness Brownian motion to benefit the contraction of the muscle overall, but the particle in this first model is in an idealized environment. In our bodies, it’s submerged in a fluid carrying many different ions and energy-bearing molecules in solution. That’s the last piece of the puzzle for the single-motor, nano-scale models of molecular motors.”

The second extension, stated Culver, is to repeat this study with a full 3-D model, paving the way to scaling up to practical designs.

Also notable is the fact that because this research is so young, ARL researchers used this project to establish relationships with other investigators in the academic community.

“Leaning on their expertise will be critical in the years to come, and we’ve done a great job of reaching out to faculty members and researchers from places like the University of Washington, Duke University and Carnegie Mellon University,” Culver said.

According to Culver, taking this research project into the next steps with help from collaborative partners will lead to tremendous capabilities for future Soldiers in combat, a critical requirement considering the nature of the ever-changing battlefield.

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

A Dynamic Escape Problem of Molecular Motors by Dean Culver, Bryan Glaz, Samuel Stanton. J Biomech Eng. Paper No: BIO-18-1527 https://doi.org/10.1115/1.4044580 Published Online: August 1, 2019

This paper is behind a paywall.

Finding killer bacteria with quantum dots and a smartphone

An August 5, 2019 news item on Nanowerk announces a new technology for detecting killer bacteria (Note: A link has been removed),

A combination of off-the-shelf quantum dots and a smartphone camera soon could allow doctors to identify antibiotic-resistant bacteria in just 40 minutes, potentially saving patient lives.

Staphylococcus aureus (golden staph), is a common form of bacterium that causes serious and sometimes fatal conditions such as pneumonia and heart valve infections. Of particular concern is a strain that does not respond to methicillin, the antibiotic of first resort, and is known as methicillin-resistant S. aureus, or MRSA.

Recent reports estimate that 700 000 deaths globally could be attributed to antimicrobial resistance, such as methicillin-resistance. Rapid identification of MRSA is essential for effective treatment, but current methods make it a challenging process, even within well-equipped hospitals.

Soon, however, that may change, using nothing except existing technology.

Researchers from Macquarie University and the University of New South Wales, both in Australia, have demonstrated a proof-of-concept device that uses bacterial DNA to identify the presence of Staphylococcus aureus positively in a patient sample – and to determine if it will respond to frontline antibiotics.

An August 12,2019 Macquarie University press release (also on EurekAlert but published August 4, 2019), which originated the news item, delves into the work,

In a paper published in the international peer-reviewed journal Sensors and Actuators B: Chemical the Macquarie University team of Dr Vinoth Kumar Rajendran, Professor Peter Bergquist and Associate Professor Anwar Sunna with Dr Padmavathy Bakthavathsalam (UNSW) reveal a new way to confirm the presence of the bacterium, using a mobile phone and some ultra-tiny semiconductor particles known as quantum dots.

“Our team is using Synthetic Biology and NanoBiotechnology to address biomedical challenges. Rapid and simple ways of identifying the cause of infections and starting appropriate treatments are critical for treating patients effectively,” says Associate Professor Anwar Sunna, head of the Sunna Lab at Macquarie University.

“This is true in routine clinical situations, but also in the emerging field of personalised medicine.”

The researchers’ approach identifies the specific strain of golden staph by using a method called convective polymerase chain reaction (or cPCR). This is a derivative of a widely -employed technique in which a small segment of DNA is copied thousands of times, creating multiple samples suitable for testing.

Vinoth Kumar and colleagues then subject the DNA copies to a process known as lateral flow immunoassay – a paper-based diagnostic tool used to confirm the presence or absence of a target biomarker. The researchers use probes fitted with quantum dots to detect two unique genes, that confirms the presence of methicillin resistance in golden staph

A chemical added at the PCR stage to the DNA tested makes the sample fluoresce when the genes are detected by the quantum dots – a reaction that can be captured easily using the camera on a mobile phone.

The result is a simple and rapid method of detecting the presence of the bacterium, while simultaneously ruling first-line treatment in or out.

Although currently at proof-of-concept stage, the researchers say their system which is powered by a simple battery is suitable for rapid detection in different settings.

“We can see this being used easily not only in hospitals, but also in GP clinics and at patient bedsides,” says lead author, Macquarie’s Vinoth Kumar Rajendran.

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

Smartphone detection of antibiotic resistance using convective PCR and a lateral flow assay by Vinoth Kumar Rajendran, Padmavathy Bakthavathsalam, Peter L.Bergquist, Anwar Sunna. Sensors and Actuators B: Chemical Volume 298, 1 November 2019,126849 DOI: https://doi.org/10.1016/j.snb.2019.126849 Available online 23 July 2019

This paper is behind a paywall.

Teaching molecular and synthetic biology in grades K-12

This* story actually started in 2018 with an August 1, 2018 Harvard University news release (h/t Aug. 1, 2018 news item on phys.org) by Leslie Brownell announcing molecular and synthetic biology educational kits that been tested in the classroom. (In 2019, a new kit was released but more about that later.)

As biologists have probed deeper into the molecular and genetic underpinnings of life, K-12 schools have struggled to provide a curriculum that reflects those advances. Hands-on learning is known to be more engaging and effective for teaching science to students, but even the most basic molecular and synthetic biology experiments require equipment far beyond an average classroom’s budget, and often involve the use of bacteria and other substances that can be difficult to manage outside a controlled lab setting.

Now, a collaboration between the Wyss Institute at Harvard University, MIT [Massachusetts Institute of Technology], and Northwestern University has developed BioBits, new educational biology kits that use freeze-dried cell-free (FD-CF) reactions to enable students to perform a range of simple, hands-on biological experiments. The BioBits kits introduce molecular and synthetic biology concepts without the need for specialized lab equipment, at a fraction of the cost of current standard experimental designs. The kits are described in two papers published in Science Advances [2018].

“The main motivation in developing these kits was to give students fun activities that allow them to actually see, smell, and touch the outcomes of the biological reactions they’re doing at the molecular level,” said Ally Huang, a co-first author on both papers who is an MIT graduate student in the lab of Wyss Founding Core Faculty member Jim Collins, Ph.D. “My hope is that they will inspire more kids to consider a career in STEM [science, technology, engineering, and math] and, more generally, give all students a basic understanding of how biology works, because they may one day have to make personal or policy decisions based on modern science.”

Synthetic and molecular biology frequently make use of the cellular machinery found in E. coli bacteria to produce a desired protein. But this system requires that the bacteria be kept alive and contained for an extended period of time, and involves several complicated preparation and processing steps. The FD-CF reactions pioneered in Collins’ lab for molecular manufacturing, when combined with innovations from the lab of Michael Jewett, Ph.D. at Northwestern University, offer a solution to this problem by removing bacteria from the equation altogether.

“You can think of it like opening the hood of a car and taking the engine out: we’ve taken the ‘engine’ that drives protein production out of a bacterial cell and given it the fuel it needs, including ribosomes and amino acids, to create proteins from DNA outside of the bacteria itself,” explained Jewett, who is the Charles Deering McCormick Professor of Teaching Excellence at Northwestern University’s McCormick School of Engineering and co-director of Northwestern’s Center for Synthetic Biology, and co-corresponding author of both papers. This collection of molecular machinery is then freeze-dried into pellets so that it becomes shelf-stable at room temperature. To initiate the transcription of DNA into RNA and the translation of that RNA into a protein, a student just needs to add the desired DNA and water to the freeze-dried pellets.

The researchers designed a range of molecular experiments that can be performed using this system, and coupled each of them to a signal that the students can easily detect with their sense of sight, smell, or touch. The first, called BioBits Bright, contains six different freeze-dried DNA templates that each encode a protein that fluoresces a different color when illuminated with blue light. To produce the proteins, students simply add these DNA templates and water to the FD-CF machinery and put the reactions in an inexpensive incubator (~$30) for several hours, and then view them with a blue light illuminator (~$15). The students can also design their own experiments to produce a desired collection of colors that they can then arrange into a visual image, a bit like using a Light Brite ©. “Challenging the students to build their own in vitro synthetic programs also allows educators to start to talk about how synthetic biologists might control biology to make important products, such as medicines or chemicals,” explained Jessica Stark, an NSF Graduate Research Fellow in the Jewett lab at Northwestern University who is co-first author on both papers.

An expansion of the BioBits Bright kit, called BioBits Explorer, includes experiments that engage the senses of smell and touch and allow students to probe their environment using designer synthetic biosensors. In the first experiment, the FD-CF reaction pellets contain a gene that drives the conversion of isoamyl alcohol to isoamyl acetate, a compound that produces a strong banana odor. In the second experiment, the FD-CF reactions contain a gene coding for the enzyme sortase, which recognizes and links specific segments of proteins in a liquid solution together to form a squishy, semi-solid hydrogel, which the students can touch and manipulate. The third module uses another Wyss technology, the toehold switch sensor, to identify DNA extracted from a banana or a kiwi. The sensors are hairpin-shaped RNA molecules designed such that when they bind to a “trigger” RNA, they spring open and reveal a genetic sequence that produces a fluorescent protein. When fruit DNA is added to the sensor-containing FD-CF pellets, only the sensors that are designed to open in the presence of each fruit’s RNA will produce the fluorescent protein.

The researchers tested their BioBits kits in the Chicago Public School system, and demonstrated that students and teachers were able to perform the experiments in the kits with the same success as trained synthetic biology researchers. In addition to refining the kits’ design so that they can one day provide them to classrooms around the world, the authors hope to create an open-source online database where teachers and students can share their results and ideas for ways to modify the kits to explore different biological questions.

“Synthetic biology is going to be one of the defining technologies of the century, and yet it has been challenging to teach the fundamental concepts of the field in K-12 classrooms given that such efforts often require expensive, complicated equipment,” said Collins, who is a co-corresponding author of both papers and also the Termeer Professor of Medical Engineering & Science at MIT. “We show that it is possible to use freeze-dried, cell-free extracts along with freeze-dried synthetic biology components to conduct innovative educational experiments in classrooms and other low-resource settings. The BioBits kits enable us to expose young kids, older kids, and even adults to the wonders of synthetic biology and, as a result, are poised to transform science education and society.

“All scientists are passionate about what they do, and we are frustrated by the difficulty our educational system has had in inciting a similar level of passion in young people. This BioBits project demonstrates the kind of out-of-the-box thinking and refusal to accept the status quo that we value and cultivate at the Wyss Institute, and we all hope it will stimulate young people to be intrigued by science,” said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School (HMS) and the Vascular Biology Program at Boston Children’s Hospital, as well as Professor of Bioengineering at Harvard’s John A. Paulson School of Engineering and Applied Sciences (SEAS). “It’s exciting to see this project move forward and become available to biology classrooms worldwide and, hopefully some of these students will pursue a path in science because of their experience.”

Additional authors of the papers include Peter Nguyen, Ph.D., Nina Donghia, and Tom Ferrante from the Wyss Institute; Melissa Takahashi, Ph.D. and Aaron Dy from MIT; Karen Hsu and Rachel Dubner from Northwestern University; Keith Pardee, Ph.D., Assistant Professor at the University of Toronto; and a number of teachers and students in the Chicago school system including: Mary Anderson, Ada Kanapskyte, Quinn Mucha, Jessica Packett, Palak Patel, Richa Patel, Deema Qaq, Tyler Zondor, Julie Burke, Tom Martinez, Ashlee Miller-Berry, Aparna Puppala, Kara Reichert, Miriam Schmid, Lance Brand, Lander Hill, Jemima Chellaswamy, Nuhie Faheem, Suzanne Fetherling, Elissa Gong, Eddie Marie Gonzales, Teresa Granito, Jenna Koritsaris, Binh Nguyen, Sujud Ottman, Christina Palffy, Angela Patel, Sheila Skweres, Adriane Slaton, and TaRhonda Woods.

This research was supported by the Army Research Office, the National Science Foundation, the Air Force Research Laboratory Center of Excellence Grant, The Defense Threat Reduction Agency Grant, the David and Lucile Packard Foundation, the Camille Dreyfus Teacher-Scholar Program, the Wyss Institute at Harvard University, the Paul G. Allen Frontiers Group, The Air Force Office of Scientific Research, and the Natural Sciences and Engineering Council of Canada. [emphases mine]

Well, that list of funding agencies is quite interesting. The US Army and Air Force but not the Navy? As for what the Natural Sciences and Engineering Council of Canada is doing on that list, I can only imagine why.

This is what they were doing in 2018,

Now for the latest update, a May 7, 2019 news item on phys.org announces the BioBits Kits have been expanded,

How can high school students learn about a technology as complex and abstract as CRISPR? It’s simple: just add water.

A Northwestern University-led team has developed BioBits, a suite of hands-on educational kits that enable students to perform a range of biological experiments by adding water and simple reagents to freeze-dried cell-free reactions. The kits link complex biological concepts to visual, fluorescent readouts, so students know—after a few hours and with a single glance—the results of their experiments.

A May 7, 2019 Northwestern University news release (also on EurekAlert and received via email) by Amanda Morris, which originated the news item, provides more details,

After launching BioBits last summer, the researchers are now expanding the kit to include modules for CRISPR [clustered regularly interspaced short palindromic repeats] and antibiotic resistance. A small group of Chicago-area teachers and high school students just completed the first pilot study for these new modules, which include interactive experiments and supplementary materials exploring ethics and strategies.

“After we unveiled the first kits, we next wanted to tackle current topics that are important for society,” said Northwestern’s Michael Jewett, principal investigator of the study. “That led us to two areas: antibiotic resistance and gene editing.”

Called BioBits Health, the new kits and pilot study are detailed in a paper published today (May 7 [2019]) in the journal ACS Synthetic Biology.

Jewett is a professor of chemical and biological engineering in Northwestern’s McCormick School of Engineering and co-director of Northwestern’s Center for Synthetic Biology. Jessica Stark, a graduate student in Jewett’s laboratory, led the study.

Test in a tube

Instead of using live cells, the BioBits team removed the essential cellular machinery from inside the cells and freeze-dried them for shelf stability. Keeping cells alive and contained for an extended period of time involves several complicated, time-consuming preparation and processing steps as well as expensive equipment. Freeze-dried cell-free reactions bypass those complications and costs.

“These are essentially test-tube biological reactions,” said Stark, a National Science Foundation graduate research fellow. “We break the cells open and use their guts, which still contain all of the necessary biological machinery to carry out a reaction. We no longer need living cells to demonstrate biology.”

This method to harness biological systems without intact, living cells became possible over the last two decades thanks to multiple innovations, including many in cell-free synthetic biology by Jewett’s lab. Not only are these experiments doable in the classroom, they also only cost pennies compared to standard high-tech experimental designs.

“I’m hopeful that students get excited about engineering biology and want to learn more,” Jewett said.

Conquering CRISPR

One of the biggest scientific breakthroughs of the past decade, CRISPR (pronounced “crisper”) stands for Clustered Regularly Interspaced Short Palindromic Repeats. The powerful gene-editing technology uses enzymes to cut DNA in precise locations to turn off or edit targeted genes. It could be used to halt genetic diseases, develop new medicines, make food more nutritious and much more.

BioBits Health uses three components required for CRISPR: an enzyme called the Cas9 protein, a target DNA sequence encoding a fluorescent protein and an RNA molecule that targets the fluorescent protein gene. When students add all three components — and water — to the freeze-dried cell-free system, it creates a reaction that edits, or cuts, the DNA for the fluorescent protein. If the DNA is cut, the system does not glow. If the DNA is not cut, the fluorescent protein is made, and the system glows fluorescent.

“We have linked this abstract, really advanced biological concept to the presence or absence of a fluorescent protein,” Stark said. “It’s something students can see, something they can visually understand.”

The curriculum also includes activities that challenge students to consider the ethical questions and dilemmas surrounding the use of gene-editing technologies.

“There is a lot of excitement about being able to edit genomes with these technologies,” Jewett said. “BioBits Health calls attention to a lot of important questions — not only about how CRISPR technology works but about ethics that society should be thinking about. We hope that this promotes a conversation and dialogue about such technologies.”

Reducing resistance

Jewett and Stark are both troubled by a prediction that, by the year 2050, drug-resistant bacterial infections could outpace cancer as a leading cause of death. This motivated them to help educate the future generation of scientists about how antibiotic resistance emerges and inspire them to take actions that could help limit the emergence of resistant bacteria.
In this module, students run two sets of reactions to produce a glowing fluorescent protein — one set with an antibiotic resistance gene and one set without. Students then add antibiotics. If the experiment glows, the fluorescent protein has been made, and the reaction has become resistant to antibiotics. If the experiment does not glow, then the antibiotic has worked.

“Because we’re using cell-free systems rather than organisms, we can demonstrate drug resistance in a way that doesn’t create drug-resistant bacteria,” Stark explained. “We can demonstrate these concepts without the risks.”

A supporting curriculum piece challenges students to brainstorm and research strategies for slowing the rate of emerging antibiotic resistant strains.

Part of something cool

After BioBits was launched in summer 2018, 330 schools from around the globe requested prototype kits for their science labs. The research team, which includes members from Northwestern and MIT, has received encouraging feedback from teachers, students and parents.

“The students felt like scientists and doctors by touching and using the laboratory materials provided during the demo,” one teacher said. “Even the students who didn’t seem engaged were secretly paying attention and wanted to take their turn pipetting. They knew they were part of something really cool, so we were able to connect with them in a way that was new to them.”

“My favorite part was using the equipment,” a student said. “It was a fun activity that immerses you into what top scientists are currently doing.”

###

The study, “BioBits Health: Classroom activities exploring engineering, biology and human health with fluorescent readouts,” was supported by the Army Research Office (award number W911NF-16-1-0372), the National Science Foundation (grant numbers MCB-1413563 and MCB-1716766), the Air Force Research Laboratory Center of Excellence (grant number FA8650-15-2-5518), the Defense Threat Reduction Agency (grant number HDTRA1-15-10052/P00001), the Department of Energy (grant number DE-SC0018249), the Human Frontiers Science Program (grant number RGP0015/2017), the David and Lucile Packard Foundation, the Office of Energy Efficiency and Renewable Energy (grant number DE-EE008343) and the Camille Dreyfus Teacher-Scholar Program. [emphases mine]

This is an image you’ll find in the abstract for the 2019 paper,

[downloaded from https://pubs.acs.org/doi/10.1021/acssynbio.8b00381]

Here are links and citations for the 2018 papers and the 2019 paper,

BioBits™ Explorer: A modular synthetic biology education kit by Ally Huang, Peter Q. Nguyen, Jessica C. Stark, Melissa K. Takahashi, Nina Donghia, Tom Ferrante, Aaron J. Dy, Karen J. Hsu, Rachel S. Dubner, Keith Pardee, Michael C. Jewett, and James J. Collins. Science Advances 01 Aug 2018: Vol. 4, no. 8, eaat5105 DOI: 10.1126/sciadv.aat5105

BioBits™ Bright: A fluorescent synthetic biology education kit by Jessica C. Stark, Ally Huang, Peter Q. Nguyen, Rachel S. Dubner, Karen J. Hsu, Thomas C. Ferrante, Mary Anderson, Ada Kanapskyte, Quinn Mucha, Jessica S. Packett, Palak Patel, Richa Patel, Deema Qaq, Tyler Zondor, Julie Burke, Thomas Martinez, Ashlee Miller-Berry, Aparna Puppala, Kara Reichert, Miriam Schmid, Lance Brand, Lander R. Hill, Jemima F. Chellaswamy, Nuhie Faheem, Suzanne Fetherling, Elissa Gong, Eddie Marie Gonzalzles, Teresa Granito, Jenna Koritsaris, Binh Nguyen, Sujud Ottman, Christina Palffy, Angela Patel, Sheila Skweres, Adriane Slaton, TaRhonda Woods, Nina Donghia, Keith Pardee, James J. Collins, and Michael C. Jewett. Science Advances 01 Aug 2018: Vol. 4, no. 8, eaat5107 DOI: 10.1126/sciadv.aat5107

BioBits Health: Classroom Activities Exploring Engineering, Biology, and Human Health with Fluorescent Readouts by Jessica C. Stark, Ally Huang, Karen J. Hsu, Rachel S. Dubner, Jason Forbrook, Suzanne Marshalla, Faith Rodriguez, Mechelle Washington, Grant A. Rybnicky, Peter Q. Nguyen, Brenna Hasselbacher, Ramah Jabri, Rijha Kamran, Veronica Koralewski, Will Wightkin, Thomas Martinez, and Michael C. Jewett. ACS Synth. Biol., Article ASAP
DOI: 10.1021/acssynbio.8b00381 Publication Date (Web): March 29, 2019

Copyright © 2019 American Chemical Society

Both of the 2018 papers appear to be open access while the 2019 paper is behind a paywall.

Should you be interested in acquiring a BioBits kit, you can check out the BioBits website. As for ‘conguering’ CRISPR, do we really need to look at it that way? Maybe a more humble appraoch could work just as well or even better, eh?

*’is’ removed from sentence on May 9, 2019.

Altered virus spins gold into beads

They’re not calling this synthetic biology but I’ m pretty sure that altering a virus gene so the virus can spin gold (Rumpelstiltskin anyone?) qualifies. From an August 24, 2018 news item on ScienceDaily,

The race is on to find manufacturing techniques capable of arranging molecular and nanoscale objects with precision.

Engineers at the University of California, Riverside, have altered a virus to arrange gold atoms into spheroids measuring a few nanometers in diameter. The finding could make production of some electronic components cheaper, easier, and faster.

An August 23, 2018 University of California at Riverside (UCR) news release (also on EurekAlett) by Holly Ober, which originated the news item, adds detail,

“Nature has been assembling complex, highly organized nanostructures for millennia with precision and specificity far superior to the most advanced technological approaches,” said Elaine Haberer, a professor of electrical and computer engineering in UCR’s Marlan and Rosemary Bourns College of Engineering and senior author of the paper describing the breakthrough. “By understanding and harnessing these capabilities, this extraordinary nanoscale precision can be used to tailor and build highly advanced materials with previously unattainable performance.”

Viruses exist in a multitude of shapes and contain a wide range of receptors that bind to molecules. Genetically modifying the receptors to bind to ions of metals used in electronics causes these ions to “stick” to the virus, creating an object of the same size and shape. This procedure has been used to produce nanostructures used in battery electrodes, supercapacitors, sensors, biomedical tools, photocatalytic materials, and photovoltaics.

The virus’ natural shape has limited the range of possible metal shapes. Most viruses can change volume under different scenarios, but resist the dramatic alterations to their basic architecture that would permit other forms.

The M13 bacteriophage, however, is more flexible. Bacteriophages are a type of virus that infects bacteria, in this case, gram-negative bacteria, such as Escherichia coli, which is ubiquitous in the digestive tracts of humans and animals. M13 bacteriophages genetically modified to bind with gold are usually used to form long, golden nanowires.

Studies of the infection process of the M13 bacteriophage have shown the virus can be converted to a spheroid upon interaction with water and chloroform. Yet, until now, the M13 spheroid has been completely unexplored as a nanomaterial template.

Haberer’s group added a gold ion solution to M13 spheroids, creating gold nanobeads that are spiky and hollow.

“The novelty of our work lies in the optimization and demonstration of a viral template, which overcomes the geometric constraints associated with most other viruses,” Haberer said. “We used a simple conversion process to make the M13 virus synthesize inorganic spherical nanoshells tens of nanometers in diameter, as well as nanowires nearly 1 micron in length.”

The researchers are using the gold nanobeads to remove pollutants from wastewater through enhanced photocatalytic behavior.

The work enhances the utility of the M13 bacteriophage as a scaffold for nanomaterial synthesis. The researchers believe the M13 bacteriophage template transformation scheme described in the paper can be extended to related bacteriophages.

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

M13 bacteriophage spheroids as scaffolds for directed synthesis of spiky gold nanostructures by Tam-Triet Ngo-Duc, Joshua M. Plank, Gongde Chen, Reed E. S. Harrison, Dimitrios Morikis, Haizhou Liu, and Elaine D. Haberer. Nanoscale, 2018,10, 13055-13063 DOI: 10.1039/C8NR03229G First published on 25 Jun 2018

This paper is behind a paywall.

For another example of genetic engineering and synthetic biology, see my July 18, 2018 posting: Genetic engineering: an eggplant in Bangladesh and a synthetic biology grant at Concordia University (Canada).

For anyone unfamiliar with the Rumpelstiltskin fairytale about spinning straw into gold, see its Wikipedida entry.

Call for abstracts: Seventh annual conference on governance of emerging technologies & science (GETS)

The conference itself will be held from May 22 – 24, 2019 at Arizona State University (ASU) and the deadline for abstracts is January 31, 2019. Here’s the news straight from the January 8, 2019 email announcement,

The Seventh Annual Conference on Governance of Emerging Technologies & Science (GETS)

May 22-24, 2019 / ASU / Sandra Day O’Connor College of Law
111 E. Taylor St., Phoenix, AZ
 
The conference will consist of plenary and session presentations and discussions on regulatory, governance, legal, policy, social and ethical aspects of emerging technologies, including nanotechnology, synthetic biology, gene editing, biotechnology, genomics, personalized medicine, digital health, human enhancement, artificial intelligence, virtual reality, internet of things (IoT), blockchain and much, much more!
 
Submit Your Abstract Here: 2019 Abstract
or
Conference Website
 
Call for abstracts:
 
The co-sponsors invite submission of abstracts for proposed presentations. Submitters of abstracts need not provide a written paper, although provision will be made for posting and possible post-conference publication of papers for those who are interested. 
Abstracts are invited for any aspect or topic relating to the governance of emerging technologies, including any of the technologies listed above.
 
·         Abstracts should not exceed 500 words and must contain your name and email address.
·         Abstracts must be submitted by January 31, 2019 to be considered. 
·         The sponsors will pay for the conference registration (including all conference meals and events) for one presenter for each accepted abstract. In addition, we will have limited funds available for travel subsidies (application included in submission form).
For more informationcontact our Executive Director Josh Abbott at Josh.Abbott@asu.edu.

Good luck on your submission!

Café Scientifique Vancouver (Canada) talk on October 30th, 2018: Solving some of Canada’s grandest challenges with synthetic biology

From an October 16, 2018 Café Scientifique Vancouver announcement (received via email),

Our next café will happen on TUESDAY, OCTOBER 30TH at 7:30PM in the
back room at YAGGER’S DOWNTOWN (433 W Pender). Our speaker for the
evening will be DR. VIKRAMADITYA G. YADAV. His topic will be:

SOLVING SOME OF CANADA’S GRANDEST CHALLENGES WITH SYNTHETIC BIOLOGY

A warming climate, unrepressed mining and logging, contamination of our
water resources, the uncertain price and tight supply of crude oil and
the growing threat of epidemics are having a profound, negative impact
on the well-being of Canadians. There is an urgent need to develop and
implement sustainable manufacturing technologies that can not only meet
our material and energy needs, but also sustain our quality of life.
Romantic and unbelievable as it sounds, Nature posses all the answer to
our challenges, and the coming decades in science and engineering will
be typified by our attempts to mimic or recruit biology to address our
needs. This talk will present a vivid snapshot of current and emerging
research towards this goal and highlight some cutting-edge technologies
under development at the University of British Columbia [UBC].

When he joined the University of Waterloo as an undergraduate student in
chemical engineering, Dr. Vikramaditya G. Yadav coveted a career in
Alberta’s burgeoning petrochemical sector. He even interned at Imperial
Oil during his first summer break from university. Then, one fine
evening during second year, he stumbled upon a copy of Juan Enríquez’s
As the Future Catches You in the library and became instantly captivated
with biological engineering. His journey over the past few years has
taken him to Sanofi Pasteur [vaccines division of the multinational
pharmaceutical
company Sanofi], the Massachusetts Institute of Technology [MIT],
Harvard University, and finally, the University of British Columbia,
where he now leads a wonderful group of researchers working on
wide-ranging topics at the interface of biology, chemistry, engineering,
medicine and economics.

We hope to see you there!

Oftentimes, the speaker is asked to write up a description of their talk and assuming that’s the case and based on how it’s written, I’d say the odds are good that this will be a lively, engaging talk.

For more proof, you can check out Dr. Yadav’s description of his research interests on his UBC profile page. BTW, his research group is called The Biofoundry (at UBC).

Genetic engineering: an eggplant in Bangladesh and a synthetic biology grant at Concordia University (Canada)

I have two bits of genetic engineering news.

Eggplants in Bangladesh

I always marvel at their beauty,

Bt eggplant is the first genetically engineered food crop to be successfully introduced in South Asia. The crop is helping some of the world’s poorest farmers feed their families and communities while reducing the use of pesticides. Photo by Cornell Alliance for Science.

A July 17, 2018 news item on phys.org describes a genetic engineering application,

Ansar Ali earned just 11,000 taka – about $130 U.S. dollars – from eggplant he grew last year in Bangladesh. This year, after planting Bt eggplant, he brought home more than double that amount, 27,000 taka. It’s a life-changing improvement for a subsistence farmer like Ali.

Bt eggplant, or brinjal as it’s known in Bangladesh, is the first genetically engineered food crop to be successfully introduced in South Asia. Bt brinjal is helping some of the world’s poorest farmers to feed their families and communities, improve profits and dramatically reduce pesticide use. That’s according to Tony Shelton, Cornell professor of entomology and director of the Bt brinjal project funded by the United States Agency for International Development (USAID). Shelton and Jahangir Hossain, the country coordinator for the project in Bangladesh, lead the Cornell initiative to get these seeds into the hands of the small-scale, resource-poor farmers who grow a crop consumed daily by millions of Bangladeshis.

A July 11, 2018 Cornell University news release by Krisy Gashler, which originated the news item, expands on the theme (Note: Links have been removed),

Bt brinjal was first developed by the Indian seed company Mahyco in the early 2000s. Scientists inserted a gene from the bacterium Bacillus thuringiensis (thus the name, Bt) into nine brinjal varieties. The plants were engineered to resist the fruit and shoot borer, a devastating insect whose larvae bore into the stem and fruit of an eggplant. The insects cause up to 80 percent crop loss.

The Bt protein produced by the engineered eggplant causes the fruit and shoot borer larva to stop feeding, but is safe for humans consuming the eggplant, as proven through years of biosafety trials. In fact, Bt is commonly used by organic farmers to control caterpillars but has to be sprayed frequently to be effective. The Bt eggplant produces essentially the same protein as in the spray. More than 80 percent of field corn and cotton grown in the U.S. contains a Bt gene for insect control.

“Farmers growing Bt brinjal in Bangladesh are seeing three times the production of other brinjal varieties, at half the production cost, and are getting better prices at the market,” Hossain said.

A recent survey found 50 percent of farmers in Bangladesh said that they experienced illness due to the intense spraying of insecticides. Most farmers work in bare feet and without eye protection, leading to pesticide exposure that causes skin and eye irritation, and vomiting.

“It’s terrible for these farmers’ health and the health of the environment to spray so much,” said Shelton, who found that pesticide use on Bt eggplant was reduced as much as 92 percent in commercial Bt brinjal plantings. “Bt brinjal is a solution that’s really making a difference in people’s lives.”

Alhaz Uddin, a farmer in the Tangail district, made 6,000 taka growing traditional brinjal, but had to spend 4,000 taka on pesticides to combat fruit and shoot borer.

“I sprayed pesticides several times in a week,” he said. “I got sick many times during the spray.”

Mahyco initially wanted to introduce Bt brinjal in India and underwent years of successful safety testing. But in 2010, due to pressure from anti-biotechnology groups, the Indian minister of the environment placed a moratorium on the seeds. It is still in effect today, leaving brinjal farmers there without the effective and safe method of control available to their neighbors in Bangladesh.

Even before the Indian moratorium, Cornell scientists hosted delegations from Bangladesh that wanted to learn about Bt brinjal and the Agricultural Biotechnology Support Project II (ABSP II), a consortium of public and private institutions in Asia and Africa intended to help with the commercial development, regulatory approval and dissemination of bio-engineered crops, including Bt brinjal.

Cornell worked with USAID, Mahyco and the Bangladesh Agricultural Research Institute to secure regulatory approval, and in 2014 the Bangladeshi government distributed a small number of Bt brinjal plants to 20 farmers in four districts. The next year 108 farmers grew Bt brinjal, and the following year the number of farmers more than doubled to 250. In 2017 the number increased to 6,512 and in 2018 to 27,012. The numbers are likely even higher, according to Shelton, as there are no constraints against farmers saving seeds and replanting.

“Farmers who plant Bt brinjal are required to plant a small perimeter of traditional brinjal around the Bt variety; research has shown that the insects will infest plants in the buffer area, and this will slow their evolutionary development of resistance to the Bt plants,” Shelton said.

In a March 2017 workshop, Bangladeshi Agriculture Minister Begum Matia Chowdhury called Bt brinjal “a success story of local and foreign collaboration.”

“We will be guided by the science-based information, not by the nonscientific whispering of a section of people,” Chowdhury said. “As human beings, it is our moral obligation that all people in our country should get food and not go to bed on an empty stomach. Biotechnology can play an important role in this effect.”

Here’s what an infested eggplant looks like,

Non-Bt eggplant infested with fruit and shoot borer. Photo by Cornell Alliance for Science

It looks more like a fig than an eggplant.

This is part of a more comprehensive project as revealed in a March 29, 2016 Cornell University news release issued on the occasion of a $4.8M, three-year grant from the U.S. Agency for International Development (USAID),

… The award supports USAID’s work under Feed the Future, the U.S. government’s global initiative to fight hunger and improve food security using agricultural science and technology.

In the Feed the Future South Asia Eggplant Improvement Partnership, Cornell will protect eggplant farmers from yield losses and improve their livelihoods in partnership with the Bangladesh Agricultural Research Institute (BARI) and the University of the Philippines at Los Baños. Eggplant, or brinjal, is a staple crop that is an important source of income and nutrition for farmers and consumers in South Asia.

Over the past decade, Cornell has led the Agricultural Biotechnology Support Project II (ABSPII), also funded by USAID, that prompted a consortium of institutions in Asia and Africa to use the tools of modern biotechnology, particularly genetic engineering, to improve crops to address major production constraints for which conventional plant breeding tools have not been effective.

In October 2013, Bangladesh became the first country in South Asia to approve commercial cultivation of a genetically engineered food crop. In February 2014, Matia Chowdhury, the Bangladesh minister of agriculture, released four varieties of Bt brinjal to 20 farmers. With the establishment of the 20 Bt brinjal demonstration plots in 2014 and 104 more in 2015, BARI reported a noticeable decrease in fruit and shoot borer infestation, increased yields, decreased use of pesticide and improved income for farmers.

The Feed the Future South Asia Eggplant Improvement Partnership addresses and integrates all elements of the commercialization process — including technology development, regulation, marketing, seed distribution, and product stewardship. It also provides strong platforms for policy development, capacity building, gender equality, outreach and communication.

Moving on from practical applications …

Canada’s synthetic biology training centre

It seems Concordia University (Montréa) is a major Canadian centre for all things ‘synthetic biological’. (from the History and Vision webpage on Concordia University’s Centre for Applied Synthetic Biology webspace),

History and vision

Emerging in 2012 from a collaboration between the Biology and Electrical and Computer Engineering Departments, the Centre received University-wide status in 2016 growing its membership to include Biochemistry, Journalism, Communication Studies, Mechanical, Industrial and Chemical Engineering.


Timeline

T17-36393-VPRG-Timeline-graphic-promo-v4

You can see the timeline does not yet include 2018 development(s). Also it started as “a collaboration between the Biology and Electrical and Computer Engineering Departments?” This suggests a vastly different approach to genetic engineering that that employed in the “eggplant” research. From a July 16, 2018 posting on the Genome Alberta blog,

The Natural Sciences and Engineering Research Council of Canada (NSERC) has committed $1.65 million dollars over six years to establish a research and training program at Concordia’s Centre for Applied Synthetic Biology.

The funds were awarded after Malcolm Whiteway (…), professor of biology and the Canada Research Chair in Microbial Genomics, and the grant application team submitted a proposal to NSERC’s Collaborative Research and Training Experience (CREATE) program.

The Synthetic Biology Applications CREATE program — or SynBioApps — will help students acquire and develop important professional skills that complement their academic education and improve their job-readiness.

‘Concordia is a natural fit’

“As the Canadian leader in synthetic biology and as the home of the country’s only genome foundry, Concordia is a natural fit for a training program in this growing area of research,” says Christophe Guy, vice-president of Research and Graduate Studies.

“In offering a program like SynBioApps, we are providing our students with both a fundamental education in science and the business skills they’ll need to transition into their professional careers.”

The program’s aims are twofold: First, it will teach students how to design and construct cells and proteins for the development of new products related to human health, green technologies, and fundamental biological investigations. Second, it will provide cross-disciplinary training and internship opportunities through the university’s District 3 Innovation Center.

SynBioApps will be open to students from biology, biochemistry, engineering, computing, and mathematics.

“The ability to apply engineering approaches to biological systems promises to revolutionize both biology and industry,” says Whiteway, who is also a member of the Centre for Applied Synthetic Biology.

“The SynBioApps program at Concordia will provide a training program to develop the students who will both investigate the biology and build these industries.”

You can find out more about Concordia’s Centre for Applied Synthetic Biology here (there are jobs listed on their home page) and you can find information about the Synthetic Biology Applications (SynBioApps) training programme here.

The CRISPR ((clustered regularly interspaced short palindromic repeats)-CAS9 gene-editing technique may cause new genetic damage kerfuffle

Setting the stage

Not unexpectedly, CRISPR-Cas9  or clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 can be dangerous as these scientists note in a July 16, 2018 news item on phys.org,

Scientists at the Wellcome Sanger Institute have discovered that CRISPR/Cas9 gene editing can cause greater genetic damage in cells than was previously thought. These results create safety implications for gene therapies using CRISPR/Cas9 in the future as the unexpected damage could lead to dangerous changes in some cells.

Reported today (16 July 2018) in the journal Nature Biotechnology, the study also revealed that standard tests for detecting DNA changes miss finding this genetic damage, and that caution and specific testing will be required for any potential gene therapies.

This CRISPR-Cas9 image reminds me of popcorn,

CRISPR-associated protein Cas9 (white) from Staphylococcus aureus based on Protein Database ID 5AXW. Credit: Thomas Splettstoesser (Wikipedia, CC BY-SA 4.0)[ downloaded from https://phys.org/news/2018-07-genome-crisprcas9-gene-higher-thought.html#jCp]

A July 16, 2018 Wellcome Sanger Institute press release (also on EurekAlert), which originated the news item, offers a little more explanation,

CRISPR/Cas9 is one of the newest genome editing tools. It can alter sections of DNA in cells by cutting at specific points and introducing changes at that location. Already extensively used in scientific research, CRISPR/Cas9 has also been seen as a promising way to create potential genome editing treatments for diseases such as HIV, cancer or sickle cell disease. Such therapeutics could inactivate a disease-causing gene, or correct a genetic mutation. However, any potential treatments would have to prove that they were safe.

Previous research had not shown many unforeseen mutations from CRISPR/Cas9 in the DNA at the genome editing target site. To investigate this further the researchers carried out a full systematic study in both mouse and human cells and discovered that CRISPR/Cas9 frequently caused extensive mutations, but at a greater distance from the target site.

The researchers found many of the cells had large genetic rearrangements such as DNA deletions and insertions. These could lead to important genes being switched on or off, which could have major implications for CRISPR/Cas9 use in therapies. In addition, some of these changes were too far away from the target site to be seen with standard genotyping methods.

Prof Allan Bradley, corresponding author on the study from the Wellcome Sanger Institute, said: “This is the first systematic assessment of unexpected events resulting from CRISPR/Cas9 editing in therapeutically relevant cells, and we found that changes in the DNA have been seriously underestimated before now. It is important that anyone thinking of using this technology for gene therapy proceeds with caution, and looks very carefully to check for possible harmful effects.”

Michael Kosicki, the first author from the Wellcome Sanger Institute, said: “My initial experiment used CRISPR/Cas9 as a tool to study gene activity, however it became clear that something unexpected was happening. Once we realised the extent of the genetic rearrangements we studied it systematically, looking at different genes and different therapeutically relevant cell lines, and showed that the CRISPR/Cas9 effects held true.”

The work has implications for how CRISPR/Cas9 is used therapeutically and is likely to re-spark researchers’ interest in finding alternatives to the standard CRISPR/Cas9 method for gene editing.

Prof Maria Jasin, an independent researcher from Memorial Slone Kettering Cancer Centre, New York, who was not involved in the study said: “This study is the first to assess the repertoire of genomic damage arising at a CRISPR/Cas9 cleavage site. While it is not known if genomic sites in other cell lines will be affected in the same way, this study shows that further research and specific testing is needed before CRISPR/Cas9 is used clinically.”

For anyone who’d like to better understand the terms gene editing and CRISPR-Cas9, the Wellcome Sanger Institute provides these explanatory webpages, What is genome editing? and What is CRISPR-Cas9?

For the more advanced, here’s a link and a citation for the paper,

Repair of double-strand breaks induced by CRISPR–Cas9 leads to large deletions and complex rearrangements by Michael Kosicki, Kärt Tomberg, & Allan Bradley. Nature Biotechnology DOI: https://doi.org/10.1038/nbt.4192 Published 16 July 2018

This paper appears to be open access.

The kerfuffle

It seems this news has affected the CRISPR market. From a July 16, 2018 article by Cale Guthrie Weissman for Fast Company,

… CRISPR could unknowingly delete or alter non-targeted genes, which could lead to myriad unintended consequences. This is especially frightening, since the technology is going to be used in human clinical trials.

Meanwhile, other scientists working with CRISPR are trying to downplay the findings, telling STAT [a life sciences and business journalism website] that there have been no reported adverse effects similar to what the study describes. The news, however, has brought about a market reaction–at least three publicly traded companies that focus on CRISPR-based therapies are in stock nosedive. Crispr Therapeutics is down by over 6%; Editas fell by over 3%; and Intellia Therapeutics dropped by over 5%. [emphasis mine]

Damage control

Gaetan Burgio (geneticist, Australian National University)  in a July 16, 2018 essay on phys.org (originating from The Conversation) suggests some calm (Note: Links have been removed),

But a new study has called into question the precision of the technique [CRISPR gene editing technology].

The hope for gene editing is that it will be able to cure and correct diseases. To date, many successes have been reported, including curing deafness in mice, and in altering cells to cure cancer.

Some 17 clinical trials in human patients are registered [emphasis mine] testing gene editing on leukaemias, brain cancers and sickle cell anaemia (where red blood cells are misshaped, causing them to die). Before implementing CRISPR technology in clinics to treat cancer or congenital disorders, we must address whether the technique is safe and accurate.

There are a few options for getting around this problem. One option is to isolate the cells we wish to edit from the body and reinject only the ones we know have been correctly edited.

For example, lymphocytes (white blood cells) that are crucial to killing cancer cells could be taken out of the body, then modified using CRISPR to heighten their cancer-killing properties. The DNA of these cells could be sequenced in detail, and only the cells accurately and specifically gene-modified would be selected and delivered back into the body to kill the cancer cells.

While this strategy is valid for cells we can isolate from the body, some cells, such as neurons and muscles, cannot be removed from the body. These types of cells might not be suitable for gene editing using Cas9 scissors.

Fortunately, researchers have discovered other forms of CRISPR systems that don’t require the DNA to be cut. Some CRISPR systems only cut the RNA, not the DNA (DNA contains genetic instructions, RNA convey the instructions on how to synthesise proteins).

As RNA [ribonucleic acid] remains in our cells only for a specific period of time before being degraded, this would allow us to control the timing and duration of the CRISPR system delivery and reverse it (so the scissors are only functional for a short period of time).

This was found to be successful for dementia in mice. Similarly, some CRISPR systems simply change the letters of the DNA, rather than cutting them. This was successful for specific mutations causing diseases such as hereditary deafness in mice.

I agree with Burgio’s conclusion (not included here) that we have a lot more to learn and I can’t help wondering why there are 17 registered human clinical trials at this point.