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A new control system for synthetic genes

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Researchers have developed a technique that could help fine-tune the production of monoclonal antibodies and other useful proteins.

Credits:  Cell image: Matthew Daniels, edited by MIT News

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A global lab for teaching and practicing synthetic biology

Photo courtesy of the researchers

via MIT News

Jan. 18, 2023

• #bioengineering
• #learning + teaching
• #synthetic biology
• #biomechanics
• #biotechnology
• David S. Kong Director, Community Biotechnology Initiative; Research Scientist
• Joseph M. Jacobson Associate Professor of Media Arts and Sciences
• Eyal Perry Research Assistant
• How to Grow (Almost) Anything - A New Model for Global Synthetic Biology Education
• Community Biotechnology

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By Becky Ham

How do you keep a hands-on synthetic biology lab class going during a pandemic?

As a unique team of MIT and Harvard Medical School faculty, teaching assistants, and students describe in a  new paper in  Nature Biotechnology , the answer involves robots and teaching assistants working together in the lab, a new way of designing experiments, and mentoring and collaboration across multiple time zones.

David S. Kong, director of the Community Biotechnology Initiative at the MIT Media Lab, teaches MAS.S64 ( How to Grow (Almost) Anything ) along with Media Lab Associate Professor Joseph Jacobson and Professor George Church of Harvard Medical School. The class was inspired by MIT Professor and Center for Bits and Atoms Director Neil Gershenfeld’s popular rapid-prototyping class MAS.863 ( How to Make (Almost) Anything ), says Kong: “The first design of the curriculum had strong metaphorical linkages to digital fabrication, but were mapped to biology. Over the years we have evolved the course to focus on building core skillsets to enable bio-enthusiasts, regardless of their previous biology experience, to really express themselves creatively using living systems.”

Participants in the latest iteration of How to Grow (Almost) Anything, or HTGAA, developed a device that assembles viruslike protein shells for possible drug delivery, a bioreactor that produces aroma compounds for astronauts, and bioart of a world map “painted” using bacteria.

The goal has always been to share the tools and knowledge of synthetic biology with the widest possible audience, moving beyond molecular biology researchers to artists, engineers, and social justice advocates, among others.

The class, especially in its new hybrid distance-learning form discussed in the paper, has the potential to “democratize synthetic biology,” at a time when “we are the verge of converting much—or all—manufacturing, from smart materials to computing, from physics- and chemistry-based to biology-based,” says Church, who is sometimes called the “father of genomics” and a leading expert in synthetic biology and personal genomics.

“We’re living in an era where many powerful technologies are developed by and often benefit a very elite and privileged sector of society,” Kong adds. “It’s my belief that for moral reasons, and also for innovation reasons, that it’s important for diverse communities all around the world to have access to these tools and technologies and to learn how to use them safely and ethically.

Robots to the rescue

The class began in 2015 as a global education initiative, and was inspired by how Gershenfeld’s course was  taught globally  in a network of what is now over  2,500 community fab labs . In its first editions, HTGAA was taught to both the Fab Lab network along with the global community biology network, which Kong helps organize via the  Global Community Bio Summit .

In 2019, Kong and Church first offered HTGAA to MIT and Harvard University graduate students. But in March 2020, midway through the course, the impending pandemic forced the nearly-full closure of MIT buildings and labs, the paper authors recall.

Without access to a wet lab to carry out experiments, and students unable to collaborate face-to-face, the instructors redesigned the course in 2021. Students now listened to virtual lectures from world-renowned researchers and ethics experts, but they also performed cloud-based experiment simulations. They learned how to code their final projects so that a liquid-handling robot at MIT could carry out their experiments, sometimes with the help of a teaching assistant, as they watched the process remotely.

The researchers had been expanding virtual aspects of the class before 2020, “but our commitment was accelerated by the otherwise unfortunate COVID-19 disaster,” says Church. “This empowered us to get much better at both making the mentoring as real as possible via flat screen and making robot ‘cloud labs’ easy and affordable.”

Students from six continents have since joined the MIT class, Kong says, many of them without a background in molecular biology. The class includes a “boot camp” in biology basics for those who need it, but “we really focus on skill building,” he adds. “You learn just enough theory that you can understand what you’re doing in the lab, but the key aspect is the hands-on, synthetic biology lab techniques that students acquire each week.”

Media Lab Research Assistant Eyal Perry SM ’21, lead author of the  Nature Biotechnology  paper, was a student in the 2020 pandemic class who returned as a teaching assistant in 2021. He said the focus on coding and simulation of experiments gave students a shared language that is unusual in lab bench biology.

“We kind of started it because of the pandemic, but I think we may have uncovered something that is fundamental for future education,” Perry says. “I think that this idea of biology through code, learning how to execute protocols and making things using robots and code, could be a new way to do things as we progress to a new era in synthetic biology.”

Global growth

The educators and students describe a future of local nodes, regional hubs and “super-core” sites that can connect students with increasing levels of technology and collaboration. In Taiwan, for instance, a HTGAA participant has already set up an active node for students, Kong says.

Kong adds that alumni have been vital in “growing the class, and as the global reach expands, we’re really building a rich and powerful innovative global learning community that goes far beyond just the course itself.”

Dominika Wawrzyniak was an HGTAA global listener in 2021 and later a global teaching assistant in 2022. Now a PhD student in biomedical engineering at New York University, she says the class is “also very rewarding for people who are already in the field itself, because you come across so many different approaches to synthetic biology that are very unique just due to the fact that people have very different backgrounds.”

Engaging designers, artists, engineers and thinkers with the practice of synthetic biology “is a better way to have a technology revolution,” Perry suggests. “We’re not trying to teach everything in this class, but really open the door, and a lot of time the door is what people are missing.”

How to Grow (Almost) Anything: a Hybrid Distance Learning Model for Global Laboratory-Based Synthetic Biology Education

Perry, Eyal, et al. "How to grow (almost) anything: a hybrid distance learning model for global laboratory-based synthetic biology education." Nature Biotechnology (2022): 1-6.

Bio Lab of the Future

DescriptionAs the scope and impact of the biotechnology revolution accelerates, the associated systems of knowledge production and innovati…

Nanostructure Fabrication by Electron and Ion Beam Patterning of Nanoparticles

Kong, D. "Nanostructure Fabrication by Electron and Ion Beam Patterning of Nanoparticles"

Open-source, community-driven microfluidics with Metafluidics

David Kong. Nature Biotechnology 35, 523–529 (2017)

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A global lab for teaching and practicing synthetic biology

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How do you keep a hands-on synthetic biology lab class going during a pandemic?

As a unique team of MIT and Harvard Medical School faculty, teaching assistants, and students describe in a new paper in Nature Biotechnology , the answer involves robots and teaching assistants working together in the lab, a new way of designing experiments, and mentoring and collaboration across multiple time zones.

David S. Kong, director of the Community Biotechnology Initiative at the MIT Media Lab, teaches MAS.S64 ( How to Grow (Almost) Anything ) along with Media Lab Associate Professor Joseph Jacobson and Professor George Church of Harvard Medical School. The class was inspired by MIT Professor and Center for Bits and Atoms Director Neil Gershenfeld’s popular rapid-prototyping class MAS.863 ( How to Make (Almost) Anything ), says Kong: “The first design of the curriculum had strong metaphorical linkages to digital fabrication, but were mapped to biology. Over the years we have evolved the course to focus on building core skillsets to enable bio-enthusiasts, regardless of their previous biology experience, to really express themselves creatively using living systems.”

Participants in the latest iteration of How to Grow (Almost) Anything, or HTGAA, developed a device that assembles viruslike protein shells for possible drug delivery, a bioreactor that produces aroma compounds for astronauts, and bioart of a world map “painted” using bacteria.

The goal has always been to share the tools and knowledge of synthetic biology with the widest possible audience, moving beyond molecular biology researchers to artists, engineers, and social justice advocates, among others.

The class, especially in its new hybrid distance-learning form discussed in the paper, has the potential to “democratize synthetic biology,” at a time when “we are the verge of converting much—or all—manufacturing, from smart materials to computing, from physics- and chemistry-based to biology-based,” says Church, who is sometimes called the “father of genomics” and a leading expert in synthetic biology and personal genomics.

“We’re living in an era where many powerful technologies are developed by and often benefit a very elite and privileged sector of society,” Kong adds. “It’s my belief that for moral reasons, and also for innovation reasons, that it’s important for diverse communities all around the world to have access to these tools and technologies and to learn how to use them safely and ethically.

Robots to the rescue

The class began in 2015 as a global education initiative, and was inspired by how Gershenfeld’s course was taught globally in a network of what is now over 2,500 community fab labs . In its first editions, HTGAA was taught to both the Fab Lab network along with the global community biology network, which Kong helps organize via the Global Community Bio Summit .

In 2019, Kong and Church first offered HTGAA to MIT and Harvard University graduate students. But in March 2020, midway through the course, the impending pandemic forced the nearly-full closure of MIT buildings and labs, the paper authors recall.

Without access to a wet lab to carry out experiments, and students unable to collaborate face-to-face, the instructors redesigned the course in 2021. Students now listened to virtual lectures from world-renowned researchers and ethics experts, but they also performed cloud-based experiment simulations. They learned how to code their final projects so that a liquid-handling robot at MIT could carry out their experiments, sometimes with the help of a teaching assistant, as they watched the process remotely.

The researchers had been expanding virtual aspects of the class before 2020, “but our commitment was accelerated by the otherwise unfortunate COVID-19 disaster,” says Church. “This empowered us to get much better at both making the mentoring as real as possible via flat screen and making robot ‘cloud labs’ easy and affordable.”

Students from six continents have since joined the MIT class, Kong says, many of them without a background in molecular biology. The class includes a “boot camp” in biology basics for those who need it, but “we really focus on skill building,” he adds. “You learn just enough theory that you can understand what you’re doing in the lab, but the key aspect is the hands-on, synthetic biology lab techniques that students acquire each week.”

Media Lab Research Assistant Eyal Perry SM ’21, lead author of the Nature Biotechnology paper, was a student in the 2020 pandemic class who returned as a teaching assistant in 2021. He said the focus on coding and simulation of experiments gave students a shared language that is unusual in lab bench biology.

“We kind of started it because of the pandemic, but I think we may have uncovered something that is fundamental for future education,” Perry says. “I think that this idea of biology through code, learning how to execute protocols and making things using robots and code, could be a new way to do things as we progress to a new era in synthetic biology.”

Global growth

The educators and students describe a future of local nodes, regional hubs and “super-core” sites that can connect students with increasing levels of technology and collaboration. In Taiwan, for instance, a HTGAA participant has already set up an active node for students, Kong says.

Kong adds that alumni have been vital in “growing the class, and as the global reach expands, we’re really building a rich and powerful innovative global learning community that goes far beyond just the course itself.”

Dominika Wawrzyniak was an HGTAA global listener in 2021 and later a global teaching assistant in 2022. Now a PhD student in biomedical engineering at New York University, she says the class is “also very rewarding for people who are already in the field itself, because you come across so many different approaches to synthetic biology that are very unique just due to the fact that people have very different backgrounds.”

Engaging designers, artists, engineers and thinkers with the practice of synthetic biology “is a better way to have a technology revolution,” Perry suggests. “We’re not trying to teach everything in this class, but really open the door, and a lot of time the door is what people are missing.”

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Harvard was one of the first institutions to offer a program to explore this exciting new field. The program’s core curriculum includes courses on the methods and logic that shape research, how to conceptualize and present research, and an introduction to the faculty’s research.

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• May 4, 2024 | MIT Uncovers Photomolecular Effect: Light Can Vaporize Water Without Heat
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MIT Uncovers Photomolecular Effect: Light Can Vaporize Water Without Heat

By David L. Chandler, Massachusetts Institute of Technology May 4, 2024

Researchers at MIT have discovered that evaporation can occur through exposure to light, not just heat. This process, observed on various water surfaces, has profound implications for climate modeling and innovative technologies like solar-driven water purification. (Artist’s concept.) Credit: SciTechDaily.com

MIT researchers have uncovered that light can induce evaporation, not just heat, demonstrating this across various natural and synthetic water surfaces. This discovery could impact climate modeling and lead to innovations in solar energy and water purification technologies.

It’s the most fundamental of processes — the evaporation of water from the surfaces of oceans and lakes, the burning off of fog in the morning sun, and the drying of briny ponds that leaves solid salt behind. Evaporation is all around us, and humans have been observing it and making use of it for as long as we have existed.

And yet, it turns out, we’ve been missing a major part of the picture all along.

Light-Induced Evaporation Discovery

In a series of painstakingly precise experiments, a team of researchers at MIT has demonstrated that heat isn’t alone in causing water to evaporate. Light, striking the water’s surface where air and water meet, can break water molecules away and float them into the air, causing evaporation in the absence of any source of heat.

The astonishing new discovery could have a wide range of significant implications. It could help explain mysterious measurements over the years of how sunlight affects clouds, and therefore affect calculations of the effects of climate change on cloud cover and precipitation. It could also lead to new ways of designing industrial processes such as solar-powered desalination or drying of materials.

Researchers at MIT have discovered a new phenomenon: that light can cause evaporation of water from its surface without the need for heat. Pictured is a lab device designed to measure the “photomolecular effect,” using laser beams. Credit: Bryce Vickmark

The findings, and the many different lines of evidence that demonstrate the reality of the phenomenon and the details of how it works, are described today in the journal PNAS, in a paper by Carl Richard Soderberg Professor of Power Engineering Gang Chen, postdocs Guangxin Lv and Yaodong Tu, and graduate student James Zhang.

The authors say their study suggests that the effect should happen widely in nature— everywhere from clouds to fogs to the surfaces of oceans, soils, and plants — and that it could also lead to new practical applications, including in energy and clean water production. “I think this has a lot of applications,” Chen says. “We’re exploring all these different directions. And of course, it also affects the basic science, like the effects of clouds on climate, because clouds are the most uncertain aspect of climate models.”

A Newfound Phenomenon

The new work builds on research reported last year , which described this new “photomolecular effect” but only under very specialized conditions: on the surface of specially prepared hydrogels soaked with water. In the new study, the researchers demonstrate that the hydrogel is not necessary for the process; it occurs at any water surface exposed to light, whether it’s a flat surface like a body of water or a curved surface like a droplet of cloud vapor.

Because the effect was so unexpected, the team worked to prove its existence with as many different lines of evidence as possible. In this study, they report 14 different kinds of tests and measurements they carried out to establish that water was indeed evaporating — that is, molecules of water were being knocked loose from the water’s surface and wafted into the air — due to the light alone, not by heat, which was long assumed to be the only mechanism involved.

The authors say their study suggests that the photomolecular effect should happen widely in nature, from clouds to fogs, ocean to soil surfaces, and plant transpiration. “I think this has a lot of applications,” Gang Chen, pictured in center, says. Chen stands with authors Guangxin Lv, on left, and James Zhang. Author Yaodong Tu is not pictured. Credit: Bryce Vickmark

One key indicator, which showed up consistently in four different kinds of experiments under different conditions, was that as the water began to evaporate from a test container under visible light, the air temperature measured above the water’s surface cooled down and then leveled off, showing that thermal energy was not the driving force behind the effect.

Other key indicators that showed up included the way the evaporation effect varied depending on the angle of the light, the exact color of the light, and its polarization. None of these varying characteristics should happen because at these wavelengths, water hardly absorbs light at all — and yet the researchers observed them.

The effect is strongest when light hits the water surface at an angle of 45 degrees. It is also strongest with a certain type of polarization, called transverse magnetic polarization. And it peaks in green light — which, oddly, is the color for which water is most transparent and thus interacts the least.

Chen and his co-researchers have proposed a physical mechanism that can explain the angle and polarization dependence of the effect, showing that the photons of light can impart a net force on water molecules at the water surface that is sufficient to knock them loose from the body of water. But they cannot yet account for the color dependence, which they say will require further study.

“We’re exploring all these different directions,” Chen says. “And of course it also affects the basic science, like the effects of clouds on climate, because clouds are the most uncertain aspect of climate models.” Credit: Bryce Vickmark

They have named this the photomolecular effect, by analogy with the photoelectric effect that was discovered by Heinrich Hertz in 1887 and finally explained by Albert Einstein in 1905. That effect was one of the first demonstrations that light also has particle characteristics, which had major implications in physics and led to a wide variety of applications, including LEDs. Just as the photoelectric effect liberates electrons from atoms in a material in response to being hit by a photon of light, the photomolecular effect shows that photons can liberate entire molecules from a liquid surface, the researchers say.

“The finding of evaporation caused by light instead of heat provides new disruptive knowledge of light-water interaction,” says Xiulin Ruan, professor of mechanical engineering at Purdue University, who was not involved in the study. “It could help us gain new understanding of how sunlight interacts with cloud, fog, oceans, and other natural water bodies to affect weather and climate. It has significant potential practical applications such as high-performance water desalination driven by solar energy. This research is among the rare group of truly revolutionary discoveries which are not widely accepted by the community right away but take time, sometimes a long time, to be confirmed.”

Because the effect is so new and unexpected, Chen says, “this phenomenon should be very general, and our experiment is really just the beginning.” Credit: Bryce Vickmark

Solving a Cloud Conundrum

The finding may solve an 80-year-old mystery in climate science. Measurements of how clouds absorb sunlight have often shown that they are absorbing more sunlight than conventional physics dictates possible. The additional evaporation caused by this effect could account for the longstanding discrepancy, which has been a subject of dispute since such measurements are difficult to make.

“Those experiments are based on satellite data and flight data,“ Chen explains. “They fly an airplane on top of and below the clouds, and there are also data based on the ocean temperature and radiation balance. And they all conclude that there is more absorption by clouds than theory could calculate. However, due to the complexity of clouds and the difficulties of making such measurements, researchers have been debating whether such discrepancies are real or not. And what we discovered suggests that hey, there’s another mechanism for cloud absorption, which was not accounted for, and this mechanism might explain the discrepancies.”

Chen says he recently spoke about the phenomenon at an American Physical Society conference, and one physicist there who studies clouds and climate said they had never thought about this possibility, which could affect calculations of the complex effects of clouds on climate. The team conducted experiments using LEDs shining on an artificial cloud chamber, and they observed heating of the fog, which was not supposed to happen since water does not absorb in the visible spectrum. “Such heating can be explained based on the photomolecular effect more easily,” he says.

Lv says that of the many lines of evidence, “the flat region in the air-side temperature distribution above hot water will be the easiest for people to reproduce.” That temperature profile “is a signature” that demonstrates the effect clearly, he says.

Zhang adds: “It is quite hard to explain how this kind of flat temperature profile comes about without invoking some other mechanism” beyond the accepted theories of thermal evaporation. “It ties together what a whole lot of people are reporting in their solar desalination devices,” which again show evaporation rates that cannot be explained by the thermal input.

The effect can be substantial. Under the optimum conditions of color, angle, and polarization, Lv says, “the evaporation rate is four times the thermal limit.”

Practical Applications and Future Research

Already, since the publication of the first paper, the team has been approached by companies that hope to harness the effect, Chen says, including for evaporating syrup and drying paper in a paper mill. The likeliest first applications will come in the areas of solar desalinization systems or other industrial drying processes, he says. “Drying consumes 20 percent of all industrial energy usage,” he points out.

Because the effect is so new and unexpected, Chen says, “This phenomenon should be very general, and our experiment is really just the beginning.” The experiments needed to demonstrate and quantify the effect are very time-consuming. “There are many variables, from understanding water itself, to extending to other materials, other liquids and even solids,” he says.

“The observations in the manuscript points to a new physical mechanism that foundationally alters our thinking on the kinetics of evaporation,” says Shannon Yee, an associate professor of mechanical engineering at Georgia Tech, who was not associated with this work. He adds, “Who would have thought that we are still learning about something as quotidian as water evaporating?”

“I think this work is very significant scientifically because it presents a new mechanism,” says University of Alberta Distinguished Professor Janet A.W. Elliott, who also was not associated with this work. “It may also turn out to be practically important for technology and our understanding of nature, because evaporation of water is ubiquitous and the effect appears to deliver significantly higher evaporation rates than the known thermal mechanism. … My overall impression is this work is outstanding. It appears to be carefully done with many precise experiments lending support for one another.”

Reference: “Photomolecular effect: Visible light interaction with air–water interface” by Guangxin Lv, Yaodong Tu, James H. Zhang and Gang Chen, 23 April 2024, Proceedings of the National Academy of Sciences . DOI: 10.1073/pnas.2320844121

The work was partly supported by an MIT Bose Award. The authors are currently working on ways to make use of this effect for water desalination, in a project funded by the Abdul Latif Jameel Water and Food Systems Lab and the MIT-UMRP program.

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