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Monday, February 25th, 2019
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| 10:59a |
An easier way to engineer plants MIT researchers have developed a new genetic tool that could make it easier to engineer plants that can survive drought or resist fungal infections. Their technique, which uses nanoparticles to deliver genes into the chloroplasts of plant cells, works with many different plant species, including spinach and other vegetables.
This new strategy could help plant biologists to overcome the difficulties involved in genetically modifying plants, which is now a complex, time-consuming process that has to be customized to the specific plant species that is being altered.
“This is a universal mechanism that works across plant species,” says Michael Strano, the Carbon P. Dubbs Professor of Chemical Engineering at MIT, about the new method.
Strano and Nam-Hai Chua, the deputy chair of the Temasek Life Sciences Laboratory at the National University of Singapore and a professor emeritus at Rockefeller University, are the senior authors of the study, which appears in the Feb. 25 issue of Nature Nanotechnology.
“This is an important first step toward chloroplast transformation,” Chua says. “This technique can be used for rapid screening of candidate genes for chloroplast expression in a wide variety of crop plants.”
This study is the first to emerge from the recently launched Singapore-MIT Alliance for Research and Technology (SMART) program in Disruptive and Sustainable Technologies for Agricultural Precision (DiSTAP), which is headed by Strano and Chua. The lead authors of the study are former MIT postdoc Seon-Yeong Kwak, who is now the scientific director of the DiSTAP program, and MIT graduate student Tedrick Thomas Salim Lew. The research team included scientists from Yield10 Bioscience.
Targeting chloroplasts
A few years ago, Strano and his colleagues discovered that by tuning the size and electrical charge of nanoparticles, they could design the nanoparticles to penetrate plant cell membranes. This mechanism, called lipid exchange envelope penetration (LEEP), allowed them to create plants that glow, by embedding nanoparticles carrying luciferase, a light-emitting protein, into their leaves.
As soon as the MIT team reported using LEEP to get nanoparticles into plants, plant biologists began asking if it could be used to genetically engineer plants, and more specifically, to get genes into chloroplasts. Plant cells have dozens of chloroplasts, so inducing the chloroplasts (instead of just the nucleus) to express genes could be a way to generate much greater quantities of a desired protein.
“Bringing genetic tools to different parts of the plant is something that plant biologists are very interested in,” Strano says. “Every time I give a talk to a plant biology community, they ask if you could use this technique to deliver genes to the chloroplast.”
The chloroplast, best known as the site of photosynthesis, contains about 80 genes, which code for proteins required to perform photosynthesis. The chloroplast also has its own ribosomes, allowing it to assemble proteins within the chloroplast. Until now, it has been very difficult for scientists to get genes into the chloroplast: The only existing technique requires using a high-pressure “gene gun” to force genes into the cells, which can damage the plant and is not very efficient.
Using their new strategy, the MIT team created nanoparticles consisting of carbon nanotubes wrapped in chitosan, a naturally occurring sugar. DNA, which is negatively charged, binds loosely to the positively charged carbon nanotubes. To get the nanoparticles into plant leaves, the researchers apply a needleless syringe filled with the particle solution to the lower side of the leaf surface. Particles enter the leaf through tiny pores called stomata, which normally control water evaporation.
Once inside the leaf, the nanoparticles pass through the plant cell wall, cell membranes, and then the double membranes of the chloroplast. After the particles get inside the chloroplast, the slightly less acidic environment of the chloroplast causes the DNA to be released from the nanoparticles. Once freed, the DNA can be translated into proteins.
In this study, the researchers delivered a gene for yellow fluorescent protein, allowing them to easily visualize which plant cells expressed the protein. They found that about 47 percent of the plant cells produced the protein, but they believe that could be increased if they could deliver more particles.
“The approach reported here certainly opens new research avenues in chloroplast-selective gene delivery for transgene expression in plants, as shown here for several mature non-model species,” says Sanjay Swarup, an associate professor of biological sciences at the National University of Singapore, who was not involved in the research.
More resilient plants
A major advantage of this approach is that it can be used across many plant species. In this study, the researchers tested it in spinach, watercress, tobacco, arugula, and Arabidopsis thaliana, a type of plant commonly used in research. They also showed that the technique is not limited to carbon nanotubes and can potentially be extended to other types of nanomaterials.
The researchers hope that this new tool will allow plant biologists to more easily engineer a variety of desirable traits into vegetables and crops. For example, agricultural researchers in Singapore and elsewhere are interested in creating leafy vegetables and crops that can grow at higher densities, for urban farming. Other possibilities include creating drought-resistant crops; engineering crops such as bananas, citrus, and coffee to be resistant to fungal infections that threaten to wipe them out; and modifying rice so that it doesn’t take up arsenic from groundwater.
Because the engineered genes are carried only in the chloroplasts, which are inherited maternally, they can be passed to offspring but can’t be transferred to other plant species.
“That’s a big advantage, because if the pollen has a genetic modification, it can spread to weeds and you can make weeds that are resistant to herbicides and pesticides. Because the chloroplast is passed on maternally, it’s not passed through the pollen and there’s a higher level of gene containment,” Lew says.
The research was funded by the National Research Foundation of Singapore and the Singapore-MIT Alliance for Research and Technology Center. | | 2:40p |
Twenty-five ways in which MIT has transformed computing This month MIT is celebrating the launch of the new $1 billion MIT Stephen A. Schwarzman College of Computing. To help commemorate the event, here’s a list of 25 ways in which MIT has already transformed the world of computing technology.
1937: Digital circuits
Master’s student Claude Shannon showed that the principles of true/false logic could be used to represent the on-off states of electric switches — a concept that served as the foundation of the field of digital circuits, and, therefore, the entire industry of digital computing itself.
1944: The digital computer
The first digital computer that could operate in real-time came out of Project Whirlwind, a initiative during World War II in which MIT worked with the U.S. Navy to develop a universal flight simulator. The device’s success led to the creation of MIT Lincoln Laboratory in 1951.
1945: Memex
Professor Vannevar Bush proposed a data system called a “Memex” that would allow a user to “store all his books, records, and communications” and retrieve them at will — a concept that inspired the early hypertext systems that led, decades later, to the World Wide Web.
1958: Functional programming
The first functional programming language was invented at MIT by Professor John McCarthy. Before LISP, programming had difficulty juggling multiple processes at once because it was “procedural” (like cooking a recipe). Functional languages let you describe required behaviors more simply, allowing work on much bigger problems than ever before.
1959: The fax
In trying to understand the words of a strongly-accented colleague over the phone, MIT student Sam Asano was frustrated that they couldn’t just draw pictures and instantly send them to each other — so he created a technology to transmit scanned material through phone lines. His fax machine was licensed to a Japanese telecom company before becoming a worldwide phenomenon.
1962: The multiplayer video game
When a PDP-1 computer arrived at MIT’s Electrical Engineering Department, a group of crafty students — including Steven “Slug” Russell from Marvin Minsky’s artificial intelligence group — went to work creating “SpaceWar!,” a space-combat video game that became very popular among early programmers and is considered the world’s first multiplayer game. (Play it here.)
1963: The password
The average person has 13 passwords — and for that you can thank MIT’s Compatible Time-Sharing System, which by most accounts established the first computer password. “We were setting up multiple terminals which were to be used by multiple persons but with each person having his own private set of files,” Professor Corby Corbato told WIRED. “Putting a password on for each individual user as a lock seemed like a very straightforward solution.”
1963: Graphical user interfaces
Nearly 50 years before the iPad, an MIT PhD student had already come up with the idea of directly interfacing with a computer screen. The “Sketchpad” developed by Ivan Sutherland PhD ’63 allowed users to draw geometric shapes with a touch-pen, pioneering the practice of “computer-assisted drafting” — which has proven vital for architects, planners, and even toddlers.
1964: Multics
MIT spearheaded the time-sharing system that inspired UNIX and laid the groundwork for many aspects of modern computing, from hierarchical file systems to buffer-overflow security. Multics furthered the idea of the computer as a “utility” to be used at any time, like water or electricity.
1969: Moon code
Margaret Hamilton led the MIT team that coded the Apollo 11 navigation system, which landed astronauts Neil Armstrong and Buzz Aldrin ScD ’63 on the moon. The robust software overrode a command to switch the flight computer’s priority system to a radar system, and no software bugs were found on any crewed Apollo missions.
1971: Email
The first email to ever travel across a computer network was sent to two computers that were right next to each other — and it came from MIT alumnus Ray Tomlinson '65 when he was working at spinoff BBN Technologies. (He’s the one you can credit, or blame, for the @ symbol.)
1973: The PC
MIT Professor Butler Lampson founded Xerox’s Palo Alto Research Center (PARC), where his work earned him the title of “father of the modern PC.” The Xerox Alto platform was used to create the first graphical user interface (GUI), the first bitmapped display, and the first “What-You-See-Is-What-You-Get” (WYSIWYG) editor.
1977: Data encryption
E-commerce was first made possible by the MIT team behind the RSA algorithm, a method of data encryption based on the concept of how difficult it is to factor huge prime numbers. Who knew that math would be why you can get your last-minute holiday shopping done?
1979: The spreadsheet
In 1979, Bob Frankston '70 and Dan Brickson '73 worked late into the night on an MIT mainframe to create VisiCalc, the first electronic spreadsheet, which sold more than 100,000 copies in its first year. Three years later, Microsoft got into the game with “Multiplan,” a program that later became Excel.
1980: Ethernet
Before there was Wi-Fi, there was Ethernet — the networking technology that lets you get online with a simple cable plug-in. Co-invented by MIT alumnus Bob Metcalfe '69, who was part of MIT’s Project MAC team and later went on to found 3Com, Ethernet helped make the Internet the fast, convenient platform that it is today.
1980: The optical mouse
Undergrad Steve Kirsch '80 was the first to patent an optical computer mouse — he had wanted to make a “pointing device” with a minimum of precision moving parts — and went on to found Mouse Systems Corp. (He also patented the method of tracking online ad impressions through click-counting.)
1983: The growth of freeware
Early AI Lab programmer Richard Stallman was a major pioneer in hacker culture and the free-software movement through his GNU Project, which set out to develop a free alternative to the Unix OS, and laid the groundwork for Linux and other important computing innovations.
1985: Spanning tree algorithm
Radia Perlman '73, SM '76, PhD '88 hates when people call her “the mother of the Internet,” but her work developing the Spanning Tree Protocol was vital for being able to route data across global computer networks. (She also created LOGO, the first programming language geared toward children.)
1994: The World Wide Web consortium (W3C)
After inventing the web, Tim Berners-Lee joined MIT and launched a consortium devoted to setting global standards for building websites, browsers, and devices. Among other things, W3C standards ensure that sites are accessible, secure, and easily “crawled” for SEO.
1999: The birth of blockchain
MIT Institute Professor Barbara Liskov’s paper on Practical Byzantine Fault Tolerance helped kickstart the field of blockchain, a widely used cryptography system. Her team’s protocol could handle high-transaction throughputs and used concepts that are vital for many of today’s blockchain platforms.
2002: Roomba
While we don’t yet have robots running errands for us, we do have robo-vacuums — and for that, we can thank MIT spinoff iRobot. The company has sold more than 20 million of its Roombas and spawned an entire industry of automated cleaning products.
2007: The mobile personal assistant
Before Siri and Alexa, there was MIT Professor Boris Katz’s StartMobile, an app that allowed users to schedule appointments, get information, and do other tasks using natural language.
2012: EdX
Led by former CSAIL director Anant Agarwal, MIT’s not-for-profit online platform with Harvard University offers free courses that have drawn more than 18 million learners around the globe, all while being open-source and nonprofit.
2013: Boston Dynamics
Professor Marc Raibert’s spinoff Boston Dynamics builds bots like “Big Dog” and “Spot Mini” that can climb, run, jump and even do back-flips. Their humanoid robot Atlas was used in the DARPA Robotics Challenge aimed at developing robots for disaster relief sites.
2016: Robots you can swallow
CSAIL Director Daniela Rus’ ingestible origami robot can unfold itself from a swallowed capsule. Using an external magnetic field, it could one day crawl across your stomach wall to remove swallowed batteries or patch wounds. | | 2:59p |
Oxygen-tracking method could improve diabetes treatment Transplanting pancreatic islet cells into patients with diabetes is a promising alternative to the daily insulin injections that many of these patients now require. These cells could act as a bioartificial pancreas, monitoring blood glucose levels and secreting insulin when needed.
For this kind of transplantation to be successful, scientists need to make sure that the implanted cells receive enough oxygen, which they need in order to produce insulin and to remain viable. MIT engineers have now devised a way to measure oxygen levels of these cells over long periods of time in living animals, which should help them predict which implants will be most effective.
In a paper appearing in the Proceedings of the National Academy of Sciences the week of Feb. 25, the researchers demonstrated that they could use this method, a specialized type of magnetic resonance imaging (MRI), to track how oxygen levels of implanted cells in the intraperitoneal (IP) cavity of mice change as they move through the cavity over a prolonged period of time.
“Our goal is to make living cellular factories that can supply drugs on demand for patients. The ability to track the oxygen supply and the location of implanted cells will help us better understand how to build and use successful therapies,” says Daniel Anderson, an associate professor in MIT’s Department of Chemical Engineering, a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES), and the senior author of the study.
Virginia Spanoudaki, the scientific director of the Koch Institute Animal Imaging and Preclinical Testing Core Facility, is the lead author of the study. Other authors include MIT postdocs Joshua Doloff and Shady Farah, research scientist Wei Huang, former research affiliate Samuel Norcross, and David H. Koch Institute Professor Robert Langer.
Better measurements
For the past several years, Anderson, Langer, and their colleagues have been developing implantable islet cells encapsulated in particles made of alginate, a starchy molecule naturally found in algae. Such particles could be used to replace the pancreatic islet cells of people with Type 1 diabetes, which do not function properly.
In an earlier study, the researchers found that larger particles, with a diameter of 1.5 millimeters, maintain their function longer than smaller particles (0.5-millimeter diameter), in part because the smaller particles tend to become surrounded by scar tissue, which blocks their access to oxygen.
However, questions still remained about the role of oxygen in the fate of these implanted cells. The particles can move through the IP space once implanted, which makes tracking them and their oxygen exposure important. Different parts of the IP space contain varying levels of oxygen, and previous studies had shown that the smaller particles tend to cluster in patches of fat, which have less oxygen, contributing to their failure.
Optical microsensors that are typically used for measuring oxygen levels in living tissue are very fragile and invasive, so the MIT team decided to try an alternative approach: fluorine MRI, a previously developed technique that other researchers have used to track living cells. While traditional MRI measures interactions between a magnetic field and hydrogen nuclei, fluorine MRI can measure similar interactions between a magnetic field and fluorine nuclei, as well as how these interactions are affected by the presence of oxygen.
To perform the study, the researchers incorporated a fluorine-containing material called a perfluorocarbon emulsion into the alginate that they normally use to encapsulate their islet cells. They tested particles with diameters of 0.5 and 1.5 millimeters, in both diabetic and nondiabetic mice. The nondiabetic mice received alginate implants with no cells inside, while the diabetic mice received implants with pancreatic islet cells.
The researchers then used fluorine MRI to measure oxygen levels in the IP space over a three-month period. At the same time, they also measured the diabetic mice’s blood glucose levels. To help them analyze the resulting data, the researchers used a machine-learning algorithm to go through all of the images and find associations between the positions of the capsules within the IP space, the oxygen levels, and the blood glucose levels of the mice.
“These kind of imaging studies involve a lot of data, and screening all of these 2-D images and making decisions about how the position of the capsules affects oxygen concentration is extremely challenging and very error prone when it’s done by a human observer,” Spanoudaki says. “So we relied on machine learning to automatically go through the images and find associations between the positions of the capsules and other parameters.”
This analysis revealed that the smaller capsules produce enough insulin to treat diabetic mice during the first 30 days of treatment, but then tend to organize in large clusters and accumulate in the fatty areas of the animals’ extremities. Once the particles become stuck in these oxygen-deprived regions, blood glucose levels rise in the mice.
The larger capsules tended to spread out over a larger area, so that some ended up in low-oxygen areas and others in high-oxygen areas. Overall, the cells secreted enough insulin to keep the diabetic mice’s blood glucose levels stable over several months.
Gordon Weir, the co-head of the Joslin Diabetes Center’s section on islet and regenerative biology, says the study sheds light on important issues regarding the optimal size of the alginate capsules used to deliver islet cells.
“The MIT group has previously shown the better transplant results in mice (and non-human primates) using capsules with a diameter of 1.5 millimeters compared with 0.5 millimeters,” says Weir, who was not involved in the research. “Now with this remarkable technique, we can see what we suspected: that the smaller capsules tend to clump more easily, which results in a more hypoxic environment that leads to impaired insulin secretion and more cell death.”
Toward a bioartificial pancreas
Sigilon Therapeutics, a company started by Langer, Anderson, and others to further develop the bioartificial pancreas, hopes to begin testing implantable islet cells in patients early next year, Anderson says. The new oxygen measurement technique could potentially be adapted for use in larger animals, including humans, which could help guide the development of future versions of the encapsulated islets, the researchers say.
“Based on measurements in larger animals, we would like to understand whether there are different ways to design the bioartificial pancreas, so that this aggregation of capsules that potentially results in reduced oxygen does not happen,” Spanoudaki says. “We are hoping to use this as a guide to make better designs for the bioartificial pancreas.”
The researchers are also hoping to adapt the fluorine MRI technology to study how oxygen levels affect other kinds of cell processes such as metastasis and immune cell activation.
The research was funded by JDRF, the Leona M. and Harry B. Helmsley Charitable Trust Foundation, the Parviz Tayebati Research Fund, and a Koch Institute Support (core) Grant from the National Cancer Institute. |
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