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Wednesday, February 22nd, 2017
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| 10:00a |
MIT undertakes Grand Challenge for innovation in global vaccine manufacturing Vaccines are among the most transformative and successful outcomes of modern medicine. For countries fortunate enough to have immunization coverage, their value can also lower or avert health care costs, increase economic productivity, and reduce poverty. The cost of producing and distributing vaccines to lower income countries still limits their availability to much of the world’s population, however.
Despite recent improvements in global vaccine coverage, the World Health Organization (WHO) estimates that 21.8 million infants worldwide did not receive complete basic immunizations in 2013. Further, of the 5.2 million deaths annually among children under the age of five, nearly one-third are preventable by vaccines. Incomplete vaccine coverage results from a number of factors, including limited resources, poor health system management, competing health priorities, and inadequate monitoring. Beyond these factors, procuring manufactured vaccines at suitable costs is an essential requirement. A substantial reduction in the cost to manufacture vaccines could help promote affordable, equitable, and sustainable immunization on a global scale, while also enabling manufacturers to develop sustainable business models around such products.
To address this manufacturing challenge, the Bill and Melinda Gates Foundation has awarded a $17.6 million Grand Challenge grant to MIT, University College London (UCL) and Kansas University to pursue an innovative research project for global health to create a next-generation manufacturing platform to produce certain vaccines for less than 15 cents a dose. The project, entitled “Ultra-low cost, Transferable Automated (ULTRA) Platform for Vaccine Manufacture,” aims to standardize the manufacturing development and production of new protein-based vaccines at globally affordable costs.
Challenge accepted
ULTRA seeks to reduce facility-related costs by combining a small physical footprint with reduced operational costs enabled by an integrated automation of the manufacturing process, to minimize labor costs and failure rates. At the heart of this endeavor is a strategic focus on recombinant protein vaccines, which rely on purified elements of a bacteria or virus to elicit immunologic protection. The manufacturing platform will accommodate chemistry, manufacturing and control development for a diverse range of components for recombinant vaccines that target diseases like Hepatitis B, HIV, HPV (an extensible risk for cervical cancer), malaria, rotavirus, and future vaccine candidates. The integrated production platform aims to produce and purify these proteins using a combination of engineered microbial cell factories and flexible approaches for purification to accommodate different vaccines and future candidates. Such manufacturing models currently exist for some biopharmaceuticals like antibody-based therapies. Today, however, solutions to manufacturing are unique for each vaccine.
“In the same ways that industry today enjoys platform manufacturing for monoclonal antibodies, we envision a new platform for current and future recombinant vaccines,” said J. Christopher Love, an MIT associate professor of chemical engineering, a member of the Koch Institute for Integrative Cancer Research, and lead investigator for the MIT team. "ULTRA should ultimately empower both a broad discovery portfolio and streamlined commercial development."
Strength in numbers
The collaboration among the academic institutions will highlight each of their strengths and expertise to develop the exciting and innovative platform. The Love laboratory, for example, brings a wide range of experience in platform-based technology development, including ongoing work under the DARPA-funded Bio-MOD program, which aims to enable systems for manufacturing on-demand. They are joined in the ULTRA effort by MIT professors Richard Braatz, the Edward R. Gilliland Professor in the Department of Chemical Engineering; and Kripa Varanasi, associate professor in the Department of Mechanical Engineering. Additional academic partners on the ULTRA program include Tarit K. Mukhopadhyay and professors Suzanne Farid and Daniel G. Bracewell from UCL and Kansas University professor David B. Volkin and research scientist Sangeeta Joshi.
The three partner academic institutions will work in tandem to develop the vaccine strains, integrated manufacturing process, and economic models to ensure that ULTRA can achieve costs of less than 15 cents per dose. If successful, this method will be tested at scale by an industrial partner who will generate clinical-grade material for a Phase 1 trial at the end of this five-year grant.
“It’s an honor to take on this important challenge with the support of this team of world-class academics,” said Love. “Together, we are committed to the global access of a powerful new approach for manufacturing low-cost vaccines.”
Learn more about the Grand Challenges initiatives, projects, and grantees at gcgh.grandchallenges.org. | | 11:00a |
3Q: US patent office’s ruling on CRISPR Last week, the U.S. Patent Trial and Appeal Board issued an important decision in a dispute over intellectual property rights to the powerful gene-editing system known as CRISPR. Using this system, researchers can make changes to a cell’s genome more easily and with greater precision than they can with other approaches. The method has great potential to advance our understanding of the biology and treatment of human disease.
The Broad Institute and MIT hold several foundational CRISPR-related patents based on research led by Feng Zhang, who is the James and Patricia Poitras Professor in Neuroscience at the McGovern Institute for Brain Research at MIT and a core member of the Broad Institute. Zhang is also an associate professor in MIT’s Department of Brain and Cognitive Sciences with a joint appointment in the Department of Biological Engineering.
The University of California at Berkeley has also filed CRISPR-based patent applications, stemming from research led by by Jennifer Doudna of UC Berkeley and Emmanuelle Charpentier, who is currently the director of the Max Planck Institute for Infection Biology in Berlin. UC Berkeley and Charpentier asked the U.S. Patent Trial and Appeal Board to declare a “patent interference” to determine who was the first to invent key CRISPR inventions, suggesting that certain claims identified by UC Berkeley in its application were to the same invention as the claims in the Broad Institute’s patents.
The Board’s Feb. 15 decision means that the Zhang patents will remain in place, although UC Berkeley is weighing its options, including the possibility of an appeal to the Federal Circuit. MIT News talked with Charles Jennings, director of the McGovern Institute Neurotechnology Program, who also oversees communcations at the Institute, to learn more about the decision and its implication for gene-editing research.
Q: What is CRISPR, and what research is being done at MIT and the Broad Institute?
A: CRISPR is a naturally occurring system by which bacteria and other microorganisms fight viral infections. CRISPR systems, such as CRISPR-Cas9 and CRISPR-Cpf1, have been harnessed as powerful and efficient tools for genome editing, with far-reaching implications for biology and medicine.
Feng Zhang, a leading pioneer in this work, and his group submitted a paper reporting genome editing in mammalian cells (including human and mouse cells), using two different CRISPR-Cas9 systems from different bacterial species to target multiple genes in the cells’ genomes. This paper, which appeared in Science on Jan. 3, 2013 (Cong et al., 2013) is now the most cited paper in the genome-editing field. Since initiating this work, which began in early 2011 soon after Zhang started as a new assistant professor, his group has continued to develop the CRISPR-Cas9 system for genome editing in eukaryotic cells. The researchers have also explored the natural diversity of CRISPR systems, which allowed them to discover new systems with advantageous properties distinct from those of CRISPR-Cas9.
Many other groups at MIT (along with thousands of other labs worldwide) are now using Zhang’s CRISPR-related tools, which he has made widely available for academic research via the Addgene website, where they have been requested more than 37,000 times.
Q: What did the U.S. Patent and Trademark Office rule on Feb. 15?
A: Zhang and his colleagues have been awarded more than 13 patents for their CRISPR-related work, which is focused primarily on the use of CRISPR in eukaryotic cells. After the first of Zhang’s patents were awarded, UC Berkeley suggested a patent proceeding known as an interference be declared, arguing that Zhang’s invention was the same as their pending claims.
On Feb. 15, the Patent Trial and Appeal Board (which is part of the U.S. Patent and Trademark Office) granted Broad's motion for no-interference-in-fact, rejecting UC Berkeley's arguments.
MIT welcomes this decision, which confirms that the patents and applications of the Broad Institute and MIT for use of CRISPR in eukaryotic cells are patentably distinct from the biochemical experiments in test tubes in the UC Berkeley filing. The Patent Trial and Appeal Board (PTAB) confirmed that Zhang’s work, which began in 2011, represents a new invention that was not obvious from the prior work of Doudna, Charpentier, and colleagues, which was confined to results in a test tube. Specifically, in the words of the PTAB decision, “one of ordinary skill in the art would not have reasonably expected a CRISPR-Cas9 system to be successful in a eukaryotic environment.”
Q: How will this decision influence gene-editing research moving forward?
A: The Broad Institute and MIT are committed to making the CRISPR technology widely available for both academic and commercial use, including human therapeutic applications. The Broad Institute, which manages Feng Zhang’s CRISPR-related intellectual property (IP) on behalf of both institutions, has developed what we have termed an “inclusive innovation” model for licensing CRISPR-related IP, in order to maximize the public benefit of this groundbreaking technology. The PTAB decision of Feb. 15 does not alter our policy, and we expect that genome-editing research will continue to move forward rapidly, with potentially transformative benefits for many fields including basic and disease-related research, agriculture, and medicine. | | 1:02p |
3Q: Julien de Wit on the discovery of seven temperate, nearby worlds Today, an international team including astronomers from MIT and the University of Liège in Belgium has announced the discovery of seven Earth-sized planets orbiting a nearby star just 39 light years from Earth. All seven planets appear to be rocky, and any one of them may harbor liquid water, as they are each within an area called the habitable zone, where temperatures are within a range suitable for sustaining liquid water on a planet’s surface.
The discovery marks a new record, as the planets make up the largest known number of habitable-zone planets orbiting a single star outside our solar system. The results are published today in the journal Nature.
Julien de Wit, a postdoc in the Department of Earth, Atmospheric, and Planetary Sciences, is heading up the team’s study of the planets’ atmospheres, the compositions of which may offer up essential clues as to whether these planets harbor signs of life. De Wit and principal investigator Michael Gillon of the University of Liège will be presenting the group’s results in a talk at MIT on February 24.
MIT News spoke with de Wit about the solar system’s new terrestrial neighbors and the possibility for life beyond our planet.
Q: What can you tell us so far about these seven planets?
A: These planets are the first found beyond the edge of our solar system, with the winning combination of being Earth-sized, temperate, and well-suited for imminent atmospheric studies. Temperate means that they can possibly harbor liquid water at their surface, while well-suited for atmospheric studies means that owing to the star they orbit and how close to the Earth it is, we will be able to get exquisite insights into their atmospheres within the next decade.
The planets are tightly packed around a small, cool, red dim star called TRAPPIST-1, located just 39 light years from Earth. TRAPPIST-1 is an ultracool dwarf star, estimated to be about 2,550 kelvins, versus our sun, which boils at around 5,800 kelvins.
The planets are so tightly packed that the seven of them are found within a distance of TRAPPIST-1 that is five times smaller than the distance from the sun to Mercury. This is so close that, depending on the planet, a year would last between 1.5 and 20 days. These planets are also most likely tidally locked, meaning that they always show the same hemisphere to their star, like the Moon does to the Earth, implying that the star never rises or sets, but stays fixed in the sky.
The small size of the star (about 11 percent the radius of the sun) is an essential part of the interest of this system. The planets were detected using the transit technique, which searches for a flux drop in a star’s brightness when a planet passes in front of it. As the flux drop is directly related to the planet-to-star area ratio, the smaller the star, the easier the detection of a planet. The signal of TRAPPIST-1’s planets is for instance about 80 times larger than what it would be if they were orbiting a star like our sun.
All of these planets are the best targets found so far to search for signs of life, and it is remarkable that they are all transiting the same star. This means that the system will allow us to study each planet in great depth, providing for the first time a rich perspective on a different planetary system than ours, and on planets around the smallest main sequence stars.
We have initiated a worldwide reconnaissance effort that spans the electromagnetic spectrum from the UV to radio, to study this system in more depth. Here at MIT, and with a large group of international experts around the world, graduate student Mary Knapp is co-leading the search for signs of planetary magnetic fields in radio, while I am leading the atmospheric reconnaissance with the Hubble Space Telescope. With observations of this system taken by Hubble last May, we have already ruled out the presence of puffy, hydrogen-dominated atmospheres around the two innermost planets, which means that they are not “mini-Neptunes” that would be uninhabitable, but are terrestrial like Mercury, Venus, Earth, and Mars. We are currently processing observations of the new planets and should gain new insights soon.
Q: Take us back to the moment of discovery. What tipped you all off that all of these planets might actually be terrestrial, and possibly even Earth-like?
A: It was such an incredible day. On Sept. 19, 2016, NASA’s Spitzer Space Telescope had started its 20-day-long monitoring of TRAPPIST-1 to search for flux drops. On Oct. 6, the first part of the data corresponding to the first 10 days of observation were released on NASA’s secured servers. Now, the fun fact is that on that day, Michael Gillon was stationed in Morocco, with a very bad internet connection, and couldn’t start playing with the data. Fortunately for his nerves, four other researchers (Jim Ingalls, Brice-Olivier Demory, Sean Carey, and I) could access the data. When I downloaded it and performed a quick processing, we had a pure, jaw-dropping, “never-seen-before” moment: By eye, I could count five more transits than expected over a short 10-day window — simply insane. After a quick iteration with Michael, we thought then that the system was containing three more planets, one being a super-Earth. But we realized quickly that what appeared to be a super-Earth was actually two planets transiting at the same time.
Our verdict: four more planets, all Earth-sized. When the second half of the data arrived on Oct. 27, we all gathered online for a debrief and cheers (with Trappist beers!). It was such an exhilarating moment.
Q: What are the chances that there may be life on one or more of these planets, and what will it take to find out?
A: We have literally no idea, but we have a chance of figuring that out soon! So far, we know that the planets could be great candidates, as they have the size of the Earth and are temperate. We now need to determine their surface conditions. This requires (1) obtaining a tight constraint on their masses, (2) assessing the type of atmospheres they have, (3) determining if they (may) actually harbor surface liquid water, and (4) searching for signs of life (i.e., biosignatures). What this will take is a significant multidisciplinary effort over the next 20 to 25 years.
When planets are close together and their orbits are in a certain spacing, they interact with each other through gravity, causing the timing of their transits to change a little as the planets tug on each other. By measuring this change, we can determine the mass of the planets. By knowing precisely the size and mass of the planets, we can determine their bulk density, and geophysicists can then help us better understand their interiors.
We will also assess their atmosphere types with a scaled-up version of our reconnaissance programs. Over the next two years, we are hoping to leverage Hubble’s capabilities to search for the presence of water- or methane-dominated atmospheres.
In the future, upcoming observatories like the James Webb Space Telescope will help us constrain the planets’ atmospheric composition, temperature, and pressure profiles — all essential information for determining the surface conditions possible over their globes.
It is important to point out here that obtaining these constraints will only be possible if we have a complete and unbiased understanding of how the light of the star going through the planet atmospheres is affected by the different components as a function of the temperature, pressure, and other gases. Then and only then, will we be able to assess the habitability of the planet.
A key part in searching for signs of life on these planets will be to determine what exactly is a sign of life, or biosignature. This is where the insight of biochemists will be essential. Fortunately, here at MIT we are already tackling this question. Indeed, Professor Sara Seager, together with postdoc Janusz Petkowski and William Bains at Cambridge University, are currently investigating the chemical space that life can occupy, to create a list of biosignatures which we will use in the future to determine if the gases detected are indicative of the presence of life on these planets. | | 11:59p |
Solar panels get a face-lift with custom designs Residential solar power is on a sharp rise in the United States as photovoltaic systems become cheaper and more powerful for homeowners. A 2012 study by the U.S. Department of Energy (DOE) predicts that solar could reach 1 million to 3.8 million homes by 2020, a big leap from just 30,000 homes in 2006.
But that adoption rate could still use a boost, according to MIT spinout Sistine Solar. “If you look at the landscape today, less than 1 percent of U.S. households have gone solar, so it’s nowhere near mass adoption,” says co-founder Senthil Balasubramanian MBA ’13.
Founded at the MIT Sloan School of Management, Sistine creates custom solar panels designed to mimic home facades and other environments, with aims of enticing more homeowners to install photovoltaic systems.
Sistine’s novel technology, SolarSkin, is a layer that can be imprinted with any image and embedded into a solar panel without interfering with the panel’s efficacy. Homeowners can match their rooftop or a grassy lawn. Panels can also be fitted with business logos, advertisements, or even a country’s flag. SolarSkin systems cost about 10 percent more than traditional panel installations. But over the life of the system, a homeowner can still expect to save more than $30,000, according to the startup.
A winner of a 2013 MIT Clean Energy Prize, Sistine has recently garnered significant media attention as a rising “aesthetic solar” startup. Last summer, one of its pilot projects was featured on the Lifetime television series “Designing Spaces,” where the panels blended in with the shingle roof of a log cabin in Hubbardston, Massachusetts.
In December, the startup installed its first residential SolarSkin panels, in a 10-kilowatt system that matches a cedar pattern on a house in Norwell, Massachusetts. Now, the Cambridge-based startup says it has 200 homes seeking installations, primarily in Massachusetts and California, where solar is in high demand.
“We think SolarSkin is going to catch on like wildfire,” Balasubramanian says. “There is a tremendous desire by homeowners to cut utility bills, and solar is finding reception with them — and homeowners care a lot about aesthetics.”
Captivating people with solar
SolarSkin is the product of the co-founders’ unique vision, combined with MIT talent that helped make the product a reality.
Balasubramanian came to MIT Sloan in 2011, after several years in the solar-power industry, with hopes of starting his own solar-power startup — a passion shared by classmate and Sistine co-founder Ido Salama MBA ’13.
One day, the two were brainstorming at the Muddy Charles Pub, when a surprisingly overlooked issue popped up: Homeowners, they heard, don’t really like the look of solar panels. That began a nebulous business mission to “captivate people’s imaginations and connect people on an emotional level with solar,” Balasubramanian says.
Recruiting Jonathan Mailoa, then a PhD student in MIT’s Photovoltaic Research Laboratory, and Samantha Holmes, a mosaic artist trained in Italy who is still with the startup, the four designed solar panels that could be embedded on massive sculptures and other 3-D objects. They took the idea to 15.366 (Energy Ventures), where “it was drilled into our heads that you have to do a lot of market testing before you build a product,” Balasubramanian says.
That was a good thing, too, he adds, because they realized their product wasn’t scalable. “We didn’t want to make a few installations that people talk about. … We [wanted to] make solar so prevalent that within our lifetime we can see the entire world convert to 100 percent clean energy,” Balasubramanian says.
The team’s focus then shifted to manufacturing solar panels that could match building facades or street fixtures such as bus shelters and information kiosks. In 2013, the idea earned the team — then officially Sistine Solar — a modest DOE grant and a $20,000 prize from the MIT Clean Energy Prize competition, “which was a game-changer for us,” Balasubramanian says.
But, while trying to construct custom-designed panels, another idea struck: Why not just make a layer to embed into existing solar panels? Recruiting MIT mechanical engineering student Jody Fu, Sistine created the first SolarSkin prototype in 2015, leading to pilot projects for Microsoft, Starwood Hotels, and other companies in the region.
That summer, after earning another DOE grant for $1 million, Sistine recruited Anthony Occidentale, an MIT mechanical engineering student who has since helped further advance SolarSkin. “We benefited from the incredible talent at MIT,” Balasubramanian says. “Anthony is a shining example of someone who resonates with our vision and has all the tools to make this a reality.”
Imagination is the limit
SolarSkin is a layer that employs selective light filtration to display an image while still transmitting light to the underlying solar cells. The ad wraps displayed on bus windows offer a good analogy: The wraps reflect some light to display an image, while allowing the remaining light through so passengers inside the bus can see out. SolarSkin achieves a similar effect — “but the innovation lies in using a minute amount of light to reflect an image [and preserve] a high-efficiency solar module,” Balasubramanian says.
To achieve this, Occidentale and others at Sistine have developed undisclosed innovations in color science and human visual perception. “We’ve come up with a process where we color-correct the minimal information we have of the image on the panels to make that image appear, to the human eye, to be similar to the surrounding backdrop of roof shingles,” Occidentale says.
As for designs, Sistine has amassed a database of common rooftop patterns in the United States, such as asphalt shingles, clay tiles, and slate, in a wide variety of colors. “So if a homeowner says, for instance, ‘We have manufactured shingles in a barkwood pattern,’ we have a matching design for that,” he says. Custom designs aren’t as popular, but test projects include commercial prints for major companies, and even Occidentale’s face on a panel.
Currently, Sistine is testing SolarSkin for efficiency, durability, and longevity at the U.S. National Renewable Energy Laboratory under a DOE grant.
The field of aesthetic solar is still nascent, but it’s growing, with major companies such as Tesla designing entire solar-panel roofs. But, as far as Balasubramanian knows, Sistine is the only company that’s made a layer that can be integrated into any solar panel, and that can display any color as well as intricate patterns and actual images.
Companies could thus use SolarSkin solar panels to double as business signs. Municipalities could install light-powering solar panels on highways that blend in with the surrounding nature. Panels with changeable advertisements could be placed on bus shelters to charge cell phones, information kiosks, and other devices. “You can start putting solar in places you typically didn’t think of before,” Balasubramanian says. “Imagination is really the only limit with this technology.” |
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