Author: MIT News

Measuring cancer cell “fitness” reveals drug susceptibility

by Anne Trafton | MIT News Office |

By studying both the physical and genomic features of cancer cells, MIT researchers have come up with a new way to investigate why some cancer cells survive drug treatment while others succumb.

Their new approach, which combines measurements of cell mass and growth rate with analysis of a cell’s gene expression, could be used to reveal new drug targets that would make cancer treatment more effective. Exploiting these targets could help knock out the defenses that cells use to overcome the original drug treatment, the researchers say.

In a paper appearing in the Nov. 28 issue of the journal Genome Biology, the researchers identified a growth signaling pathway that is active in glioblastoma cells that are resistant to an experimental type of drug known as an MDM2 inhibitor.

“By measuring a cell’s mass and growth rate immediately prior to single-cell RNA-sequencing, we can now use a cell’s ‘fitness’ to classify it as responsive or nonresponsive to a drug, and to relate this to underlying molecular pathways,” says Alex K. Shalek, the Pfizer-Laubach Career Development Assistant Professor of Chemistry, a member of MIT’s Institute for Medical Engineering and Science (IMES), an extramural member of the Koch Institute for Integrative Cancer Research, and an associate member of the Ragon and Broad Institutes.

Shalek and Scott Manalis, the Andrew and Erna Viterbi Professor in the MIT departments of Biological Engineering and Mechanical Engineering and a member of the Koch Institute, are the senior authors of the study. The paper’s lead author is Robert Kimmerling, a recent MIT PhD recipient.

Cancer cell analysis

About a decade ago, Manalis’ lab invented a technology that allows researchers to measure the mass of single cells. In recent years, they have adapted the device, which measures cells’ masses as they flow through tiny channels, so that it can also measure cell growth rates by repeatedly weighing the cells over short periods of time.

Last year, working with researchers at Dana-Farber Cancer Institute (DFCI), Manalis and his colleagues used this approach to test drug responses of tumor cells from patients with multiple myeloma, a type of blood cancer. After treating the cells with three different drugs, the researchers measured the cells’ growth rates and found they were correlated with the cells’ susceptibility to the treatment.

“Single-cell biophysical properties such as mass and growth rate provide early indicators of drug response, thereby offering the potential to delineate sensitive cells from resistant cells while they are still viable,” Manalis says.

In their new study, the researchers wanted to add a genomic component, which they hoped could help reveal why only certain cells are susceptible to a particular drug. “We wanted to be able to take those measurements and add on some of the biological context for why a cell is growing a certain way or behaving a certain way,” Kimmerling says.

To accomplish this, Kimmerling and Manalis teamed up with Shalek, who has extensive experience in sequencing the messenger RNA (mRNA) of individual cells. This information can provide a snapshot of which genes are being expressed in a single cell at a particular moment.

The researchers modified the cell-weighing system so that cells would be spaced evenly as they flowed through, making it easier to collect them one at a time when they exit the system. The cells are weighed several times over the course of 20 minutes to determine growth rate, and as soon as they reach the end of the channel, they are immediately captured and ruptured to release their RNA for analysis. Shalek’s lab then sequenced the RNA of each of the cells. This approach enabled the mass and growth rate of each cell to be directly linked to its gene expression.

Once they had the system working, the researchers collaborated with Keith Ligon and his lab at DFCI to analyze cancer cells derived from a patient with glioblastoma, an aggressive type of brain cancer. The researchers treated the cells with an MDM2 inhibitor, a type of drug that helps to boost the function of p53, a protein that helps cells stop tumor formation. Such drugs are now in clinical trials to treat glioblastoma. In animal studies, this drug has been effective against tumors, but the tumors often grow back later.

In this study, the researchers hoped to find out why some glioblastoma cells survive MDM2 treatment. They treated the cells, measured their growth rates about 16 hours after the treatment, and then sequenced their RNA. “Before the cells have lost viability, we can measure their mass and their growth rate to reveal drug response heterogeneity to that treatment, and then link that with their gene expression,” Kimmerling says.

Importantly, the researchers found subpopulations of cells that were not responsive to the drug. RNA sequencing revealed that in cells that were responsive, genes required for programmed cell death were turned on. Meanwhile, in cells that did not seem to be vulnerable to the drug, genes involved in mTOR, a signaling pathway involved in growth and survival, were turned up.

“What we’re excited about here is we now have this list of biological targets to look into,” Kimmerling says. “We can start to generate testable hypotheses from these gene expression signatures that are more highly expressed in the cells that continue to grow after drug treatment.”

Possible drug targets

The researchers now plan to explore the possibility of targeting some of the genes that were turned up on the nonresponding cells, in hopes of developing drugs that could be used together with the original MDM2 inhibitor. They also hope to adapt this approach for other types of cancers. Some, such as blood cancers, are easier to study than solid tumors, which are more difficult to separate into single cells.

“The hope is that we’ll be able to apply this technology to any sample that can be dissociated into a single-cell population,” Kimmerling says.

Another possible application of the cell-growth measurement technology is studying tumor cells from individual patients to try to predict how they will respond to a particular drug. Kimmerling, Manalis, and others have founded a company called Travera, which has licensed the technology and hopes to develop it for patient use. The company is currently not working on the RNA sequencing aspect of the technology, but that element could also be valuable to incorporate in the future, Kimmerling says.

The research was funded by the Cancer Systems Biology Consortium U54 Research Center and the Cancer Center Support (core) Grant from the National Cancer Institute; the Searle Scholars Program; the Beckman Young Investigator Program; the National Institutes of Health, including an NIH New Innovator Award; the Pew-Stewart Scholars; and a Sloan Fellowship in Chemistry.

Baglietto, Saxe, and Shoulders ensure grad students thrive

by Courtney Lesoon | Office of Graduate Education |

The journey through graduate school is rarely straight and smooth. There are challenges and setbacks, students experience varying degrees of doubt and struggle, and many redefine their goals along the way. On this winding path, the guidance of a mentor can make all the difference to a student’s sanity and success. Professors Emilio Baglietto, Rebecca Saxe, and Matthew Shoulders were nominated by their graduate students as models of great mentorship, and are among the current slate of honorees for Committed to Caring (C2C).

Emilio Baglietto: Making the connection

Professor Emilio Baglietto’s “unparalleled enthusiasm” for teaching is both contagious and formative of his students’ academic development, his advisees say. “It was during his class that I felt I actually became a nuclear engineer,” one of his them remarked.

Before coming to MIT, Baglietto worked in the nuclear engineering industry and cites the experience as being highly influential of his teaching and research style. He earned his MS in Nuclear Engineering from the University of Pisa in 2002, and his PhD in Nuclear Engineering from the Tokyo Institute of Technology in 2004. Baglietto is now an Associate Professor of Nuclear Science and Engineering at MIT.

His advisees say he is especially dedicated to helping his students make connections with the broader field of nuclear engineering. This type of ‘informal advising’ (a precept that is one of the Mentoring Guideposts identified by the C2C program) helps students to feel well-grounded and sufficiently prepared for the future. One student recounts: “Baglietto consistently encourages everyone in our research group to network broadly, and has funded our entire group to attend some of the top international research conferences. He is truly committed to our professional growth and development.”

Baglietto has also prioritized fostering a friendly and inclusive work environment (another of the C2C Mentoring Guideposts). One of Baglietto’s students noted in their nomination letter that “he creates a collaborative environment in which it is understood that each person’s opinion must be treated with respect, and that each individual contributes value to the research group as a whole.”

One of the central practices Baglietto encourages in his lab–and a tenet he learned from his middle school math teacher–is “to enjoy competition.”

“Research is not that different from sport, so don’t be afraid of competing,” he urges. “Go out and challenge other groups with your ideas, make it fun … and never be afraid of challenging yourself and your ideas!”

Rebecca Saxe: Generously present

Professor Rebecca Saxe believes science is both a pleasure and a privilege. “We get to spend our time pursuing hard elusive ideas because of our own profound curiosity,” she muses. “And it is possible for that pursuit to be intrinsically motivating and satisfying.”

That approach has informed her excellent mentorship practices in MIT’s Brain and Cognitive Sciences Department, where Saxe is the John Jarve (1978) Professor of Cognitive Neuroscience and Associate Member of the McGovern Institute for Brain Research. She received her BA in Psychology and Philosophy from Oxford University and her PhD in Cognitive Science from MIT.

Saxe’s nominators write that through her research and engagement with the public, she is “an extremely generous and kind person who is invested in making the world a more generous and kind place.”

Giving with both her time and attention, Saxe fosters a friendly and inclusive work environment (one of the C2C Mentoring Guideposts). Most notably, she welcomes to her lab collaborators of diverse academic backgrounds: “For some, working in Rebecca’s lab is an introduction to academic research,” one advisee said. “These opportunities are incredibly meaningful and result in a more diverse and rich lab environment.”

This attitude of inclusion does not stop with her lab or with academic colleagues. Consistently finding opportunities to engage with the broader public, one advisee remarked that Saxe “not only encourages lab members to organize and hold outreach events, but she herself gives talks and presentations to general audiences, such as TED talks, stage shows at the MIT Museum, and presentations associated with Cambridge Science Festival.” Her TED talk has been viewed nearly 3 million times and its transcription has been translated into 33 languages.

For Saxe, good mentorship is a crucial component of her own work. When responding about how she balances all of her responsibilities Saxe notes: “As a scientist, I do almost all of my real work in collaboration with students and post-docs. So, advising and mentoring is very compatible with my responsibility to do research.”

Matthew Shoulders: Thriving together

Shoulders encourages peer mentoring in his lab, emphasizing that “a key part of being a scientist is learning to mentor others effectively.” In order to implement this system of peer-support, Shoulders says, “I ask each student to develop their own mentoring skills and track record, and then I work with them to guide these efforts.”

In nominations letters submitted to C2C, students note that Shoulders “reminds us that being a good scientist involves not only stewarding the time and resources we have, but also caring for and supporting those we work with.”

Now the Whitehead Career Development Associate Professor in Chemistry, Shoulders earned his BS in chemistry from the Virginia Polytechnic Institute and State University and his PhD in organic chemistry from the University of Wisconsin-Madison. After a post-doctoral fellowship with the American Cancer Society at the Scripps Research Institute, Shoulders joined the MIT professoriate in 2012.

Among the good mentoring practices that Shoulders promotes in his lab is speaking openly and honestly about a healthy work-life balance (a Mentoring Guidepost). Shoulders says: “I encourage my co-workers to engage in ‘conscious prioritization,’ a process in which they should intentionally assess their priorities and time commitments to different aspects of their life, as well as the associated costs and benefits, several times a year.”

Shoulders provides his students with an open line of communication (another Mentoring Guidepost). “Early on, I learned that I could count on Matt to make himself available to chat about data, my latest crazy idea, or my existential crises about graduate school,” wrote one nominator. Often telling students to “just swing by his office,” Shoulders’ open invitation remains, even as his schedule becomes busier.

When asked for the best piece advice he could give to an MIT student, Shoulders offered: “Don’t waste time questioning yourself and whether you belong here – you do! Instead, find colleagues that support you and be courageous in pursuing your goals, whatever they may be. MIT is an awesome place, so spend your time here taking advantage of it and not worrying about success or failure.”

More on Committed to Caring (C2C)

The Committed to Caring (C2C) program is an initiative of the Office of Graduate Education and contributes to its mission of making graduate education at MIT “empowering, exciting, holistic, and transformative.”

C2C invites graduate students from across MIT’s campus to nominate professors whom they believed to be outstanding mentors. Selection criteria for the award include the scope and reach of advisor impact on the experience of graduate students, excellence in scholarship, and demonstrated commitment to diversity and inclusion.

By recognizing the human element of graduate education, C2C seeks to encourage good advising and mentorship across MIT’s campus.

A novel way to advance a better battery design

by Zach Winn | MIT News Office |

Cadenza Innovation has developed a new design that improves the performance, cost, and safety of large lithium ion batteries. Now, with an unusual strategy for disseminating that technology, the company is poised to have an impact in industries including energy grid storage, industrial machines, and electric vehicles.

Rather than produce the batteries itself, Cadenza licenses its technology to manufacturers producing batteries for diverse applications. The company also works with licensees to both optimize their manufacturing processes and sell the new batteries to end users. The strategy ensures that the four-year old company’s technology is deployed more quickly and widely than would otherwise be possible.

For Cadenza founder Christina Lampe-Onnerud, a former MIT postdoc and a battery industry veteran of more than 20 years, the goal is to help advance the industry just as the global demand for batteries reaches an inflection point.

“The crazy idea at the time [of the company’s founding] was to see if there was a different way to engage with the industry and help it accept a new technology in existing applications like cars or computers,” Lampe-Onnerud says. “Our thought was, if we really want to have an impact, we could inspire the industry to use existing capital deployed to get a better technology into the market globally and be a positive part of the climate change arena.”

With that lofty goal in mind, the Connecticut-based company has secured partnerships with organizations at every level of the battery supply chain, including suppliers of industrial minerals, original equipment manufacturers, and end users. Cadenza has demonstrated its proprietary “supercell” battery architecture in Fiat’s 500e car model and is in the process of completing a demonstration energy storage system to be used by the New York Power Authority, the largest state public utility company in the U.S., when energy demand is at its peak.

The company’s most significant partnership to date, however, was announced in September with Shenzen BAK Battery Company, one of the world’s largest lithium ion battery manufacturers. The companies announced BAK would begin mass producing batteries based on Cadenza’s supercell architecture in the first half of 2019.

The supercell architecture

Lampe-Onnerud’s extensive contacts in the lithium ion battery space and world-renown technical team have quickened the pace of Cadenza’s rise, but the underlying driver of the company’s success is simple economics: Its technology has been shown to offer manufacturers increased energy density in battery cells while reducing production costs.

The majority of rechargeable lithium ion batteries are powered by cylindrical sheets of metal known as “jelly rolls.” For use in big batteries, jelly rolls can be made either large, to limit the total cost of battery assembly, or small, to leverage a more efficient cell design that brings higher energy density. Many electric vehicle (EV) companies use large jelly rolls to avoid the durability and safety concerns that come with tightly packing small jelly rolls into a battery, which can lead to the failure of the entire battery if one jelly roll overheats.

Tesla famously achieves longer vehicle ranges by using small jelly rolls in its batteries, addressing safety issues with cooling tubes, intricate circuitry, and by spacing out each roll. But Cadenza has patented a simpler battery system it calls the “supercell,” that allows small jelly rolls to be tightly packed together into one module.

The key to the supercell is a noncombustible ceramic fiber material that each jelly roll sits in like an egg in a carton. The material helps to control temperature throughout the cell and isolate damage caused by an overheated jelly roll. A metal shunt wrapped around each jelly roll and a flame retardant layer of the supercell wall that relieves pressure in the case of a thermal event add to its safety advantages.

The enhanced safety allows Cadenza to package the jelly rolls tightly for greater energy density, and the supercell’s straightforward design, which leverages many parts that are currently manufactured at low costs and high volumes, keeps production costs down. Finally, each supercell module is designed to click together like LEGO blocks, making it possible for manufacturers to easily scale their battery sizes to fit customer needs.

Cadenza’s safety, cost, and performance features were validated during a grant program with the Advanced Research Projects Agency-Energy (ARPA-E), which gave the company nearly $4 million to test the architecture beginning in 2013.

When the supercell architecture was publicly unveiled in 2016, Lampe-Onnerud made headlines by saying it could be used to boost the range of Tesla’s cars by 70 percent. Now the goal is to get manufacturers to adopt the architecture.

“There will be many winners using this technology,” Lampe-Onnerud says. “We know we can deliver on the [safety, performance, and cost] claims. It’s going to be up to the licensee to decide how they leverage these advantages.”

At MIT, where “data gets to speak”

Lampe-Onnerud and her husband, Per Onnerud, who serves as Cadenza’s chief technology officer, held postdoctoral appointments at MIT after earning their PhDs at Uppsala University in their home country of Sweden. Lampe-Onnerud did lab work in inorganic chemistry in close collaboration with MIT materials science and mathematics professors, while Onnerud did research in the Department of Materials Science and Engineering. The experience left a strong impression on Lampe-Onnerud.

“MIT was a very formative experience,” she says. “You learn how to argue a point so that the data gets to speak. You just enable the data; there’s no spin. MIT has a special place in my heart.”

Lampe-Onnerud has maintained a strong connection with the Institute ever since, participating in alumni groups, giving guest lectures on campus, and serving as a member of the MIT Corporation visiting committee for the chemistry department — all while finding remarkable success in her career.

Lampe-Onnerud founded Boston-Power in 2004, which she grew into an internationally recognized manufacturer of batteries for consumer electronics, vehicles, and industrial applications while serving as the CEO until the company moved operations to China in 2012. In the early stages of the company, more than seven years after Lampe-Onnerud had finished her postdoc work, she discovered the enduring nature of support from the MIT community.

“We started looking for some angel investors, and one of the first groups that responded were the angels affiliated with MIT,” Lampe-Onnerud says. “We support each other because we tend to be attracted to intractable problems. It’s very much in the MIT spirit: We know, if we’re trying to solve big problems, it’s going to be difficult. So we like to collaborate.”

The high-profile experience at Boston Power earned her distinctions including the Technology Pioneer Award from the World Economic Forum, and Swedish Woman of the Year from the Swedish Women’s Educational Association. It also led some to deem her the “Queen of Batteries.”

Immediately after leaving Boston-Power, Lampe-Onnerud and her husband went to work on what would be Cadenza’s supercell architecture in their garage. They wanted to create a solution that would help lower the world’s carbon footprint, but they estimated that, at most, they’d be able to build one gigafactory every 18 months if they were to manufacture the batteries themselves. So they decided to license the technology instead.

The strategy has tradeoffs from a business perspective: Cadenza has needed to raise much less capital than Boston-Power but will allow licensees to generate topline and bottomline growth while it receives a percentage of sales. Lampe-Onnerud is clearly happy to leverage her global network and share the upside to maximize Cadenza’s impact.

“My hope is that we are able to bring people together around this technology to do things that are really important, like taking down our carbon footprint, eliminating NOx [nitrogen oxide] emissions, or improving grid efficiency,” Lampe-Onnerud says. “It’s a different way to work together, so when an element of this ecosystem wins, we all win. It has been an inspiring process.”

Chemical synthesis could produce more potent antibiotics

by Anne Trafton | MIT News Office |

Using a novel type of chemical reaction, MIT researchers have shown that they can modify antibiotics in a way that could potentially make them more effective against drug-resistant infections.

By chemically linking the antibiotic vancomycin to an antimicrobial peptide, the researchers were able to dramatically enhance the drug’s effectiveness against two strains of drug-resistant bacteria. This kind of modification is simple to perform and could be used to create additional combinations of antibiotics and peptides, the researchers say.

“Typically, a lot of steps would be needed to get vancomycin in a form that would allow you to attach it to something else, but we don’t have to do anything to the drug,” says Brad Pentelute, an MIT associate professor of chemistry and the study’s senior author. “We just mix them together and we get a conjugation reaction.”

This strategy could also be used to modify other types of drugs, including cancer drugs, Pentelute says. Attaching such drugs to an antibody or another targeting protein could make it easier for the drugs to reach their intended destinations.

Pentelute’s lab worked with Stephen Buchwald, the Camille Dreyfus Professor of Chemistry at MIT; Scott Miller, a professor of chemistry at Yale University; and researchers at Visterra, a local biotech company, on the paper, which appears in the Nov. 5 issue of Nature Chemistry. The paper’s lead authors are former MIT postdoc Daniel Cohen, MIT postdoc Chi Zhang, and MIT graduate student Colin Fadzen.

A simple reaction

Several years ago, Cohen made the serendipitous discovery that an amino acid called selenocysteine can spontaneously react with complex natural compounds without the need for a metal catalyst. Cohen found that when he mixed electron-deficient selenocysteine with the antibiotic vancomycin, the selenocysteine attached itself to a particular spot — an electron-rich ring of carbon atoms within the vancomycin molecule.

This led the researchers to try using selenocysteine as a “handle” that could be used to link peptides and small-molecule drugs. They incorporated selenocysteine into naturally occurring antimicrobial peptides — small proteins that most organisms produce as part of their immune defenses. Selenocysteine, a naturally occurring amino acid that includes an atom of selenium, is not as common as the other 20 amino acids but is found in a handful of enzymes in humans and other organisms.

The researchers found that not only were these peptides able to link up with vancomycin, but the chemical bonds consistently occurred at the same location, so all of the resulting molecules were identical. Creating such a pure product is difficult with existing methods for linking complex molecules. Furthermore, doing this kind of reaction with previously existing methods would likely require 10 to 15 steps just to chemically modify vancomycin in a way that would allow it to react with a peptide, the researchers say.

“That’s the beauty of this method,” Zhang says. “These complex molecules intrinsically possess regions that can be harnessed to conjugate to our protein, if the protein possesses the selenocysteine handle that we developed. It can greatly simplify the process.”

Dan Mandell, CEO of GRO Biosciences, says the new approach also overcomes another obstacle to this type of reaction, which is that when drugs are chemically modified to enable attachment to selenocysteine, it can weaken them.

“This paper provides an important advance on this technology by allowing attachment of unmodified drugs to targeting proteins,” says Mandell, who was not involved in the research. “This approach can help usher in a new wave of selenocysteine-mediated drug conjugates, where targeting proteins deliver potent drugs to the site of disease in a predictable fashion.”

The researchers tested conjugates of vancomycin and a variety of antimicrobial peptides (AMPs). They found that one of these molecules, a combination of vancomycin and the AMP dermaseptin, was five times more powerful than vancomycin alone against a strain of bacteria called E. faecalis. Vancomycin linked to an AMP called RP-1 was able to kill the bacterium A. baumannii, even though vancomycin alone has no effect on this strain. Both of these strains have high levels of drug resistance and often cause infections acquired in hospitals.

Modified drugs

This approach should work for linking peptides to any complex organic molecule that has the right kind of electron-rich ring, the researchers say. They have tested their method with about 30 other molecules, including serotonin and resveratrol, and found that they could be easily joined to peptides containing selenocysteine. The researchers have not yet explored how these modifications might affect the drugs’ activity.

In addition to modifying antibiotics, as they did in this study, the researchers believe they could use this technique for creating targeted cancer drugs. Scientists could use this approach to attach antibodies or other proteins to cancer drugs, helping the drugs to reach their destination without causing side effects in healthy tissue.

Adding selenocysteine to small peptides is a fairly straightforward process, the researchers say, but they are now working on adapting the method so that it can be used for larger proteins. They are also experimenting with the possibility of performing this type of conjugation reaction using the more common amino acid cysteine as a handle instead of selenocysteine.

The research was funded by the National Institutes of Health, a Damon Runyon Cancer Research Foundation Award, and a Sontag Distinguished Scientist Award.

Addressing Africa’s sustainable development

by Taylor De Leon | Civil and Environmental Engineering |

Climate change, a surging population, and increasing demand for food, housing and natural resources present Africa and the world with extraordinary challenges.

On Sept. 24, numerous experts from diverse disciplines and areas of the world convened at MIT to discuss sustainable development in Africa. The conference was hosted by the Université Mohammed VI Polytechnique-MIT Research Program (UMRP), a collaboration with the Moroccan university (UM6P) led by MIT faculty director Elfatih A. B. Eltahir, the Breene M. Kerr Professor of Hydrology and Climate in the Department of Civil and Environmental Engineering.

UMRP, which launched in 2016, is comprised of six projects led by MIT faculty, which are each built around the dissertation research of an MIT graduate student. The UMRP researchers work closely with the faculty and student colleagues from UM6P, who engage in complementary research.

The African Sustainability Conference provided a showcase for these projects, featuring presentations from MIT and UM6P faculty, researchers, and international experts on climate and water, sustainable urbanization, precision agriculture, smart chemistry, and industrial optimization for the phosphate industry. Group discussions related to critical challenges and potential opportunities within each area followed each session.

Eltahir began the conference by highlighting the significance of Africa in terms of global sustainability, noting that the substantial yet uncertain effects of climate change are already noticeable in agricultural productivity and infrastructure throughout the continent. Projections show that by 2050, Africa’s population will double from 1 billion to 2 billion people, creating an influx of urbanization.

“We are forging an honest collaboration between MIT and a like-minded research and education partner in Africa with the mission of advancing sustainability goals, while also helping build UM6P’s institutional capacity to lead by example on the continent,” expressed Eltahir.

Eltahir brings his background in hydrology and climate to his own UMRP research project, that focuses on improving water management and agricultural productivity in one of Morocco’s major river basins, the Oum-Er-Rbia watershed.

“Climate change is a major challenge for the world, especially concerning Africa. Morocco is a country that suffers from interannual rainfall variability. We are focused on looking for ways to improve management for water resources and availability,” explained Eltahir.

Morocco is highly vulnerable to heat waves and low precipitation, and those extremes are expected to intensify due to climate change. Eltahir’s research addresses these issues through a three-level modeling approach geared toward climatology and forecasting, hydrology, and operations in terms of agricultural planning and infrastructure.

He hopes the program will continue to grow, allowing for further collaboration between MIT and UM6P, students, and faculty. Furthermore, some of the tools, models, and processes that are being utilized in Morocco and greater Africa, can be applied to other regions around the world who will face similar challenges due to climate change.

In addition to Eltahir, the workshop brought together MIT professors John Fernández of the Department of Architecture, Benedetto Marelli of the Department of Civil and Environmental Engineering, Paul Barton of the Department of Chemical Engineering, and Christopher Cummins and Yogesh Surendranath of the Department of Chemistry. Including UM6P colleagues, invited international experts, and MIT graduate students, the conference highlighted efforts to implement resilience, adaptability, and sustainability into the future of African cities.

John Fernández, director of MIT’s Environmental Solutions Initiative and professor of architecture, helped launch UMRP with the focus that there is an urgency needed for long-term sustainability, in the areas of society, economy, and climate.

Through comprehensive material accounting of the needs of Moroccan cities, Fernández will be developing specific technology and policy recommendations for UM6P, providing the country with a template for long term urban sustainability.

“One of our goals is to produce a UMRP urban resource tool that would allow Morocco and greater Africa to access data and reach informed decisions about urban sustainability,” said Fernández. The tool’s engine would be developed in partnership with UM6P and the tool itself would be offered online.

The strains of urban population growth, and a predicted threefold increase in urban energy and urban land area globally is a primary motivation of the project. In addition, it is likely that low-income urban areas in Africa will be most vulnerable to the consequences of climate change due to unreliable and limited access to energy sources, water, and shelter.

“With climate change, what happens in terms of the vulnerability of lower income segments of urban population, and at what point, with extreme heat, intense precipitation or climate-induced water shortage does urban vulnerability become urban survivability?” Fernández asked.

Securing resources for the future

In addition to climate concerns, agricultural production concerns were raised as well from both MIT and UM6P experts.

Benedetto Marelli, the Paul M Cook Career Development Assistant Professor in the Department of Civil and Environmental Engineering, shared that he is focused on developing new technologies that can increase agricultural production. He stated that with a growing population, a 70 percent increase in food production will be necessary by 2050.

Marelli is in the process of creating biofertilizers that can work with the plant, to boost germination and overcome environmental stressors such as pests, disease, heat waves, and drought.

Manal Mhada, a postdoc from UM6P, presented her research on precision agriculture, and the efficient use of seeds and fertilizers. Her work focuses on human-centered solutions for Moroccan communities, and includes local farmers in her research projects.

Mhada conducts close studies of the crop quinoa, with the intention of introducing it to Morocco in order to provide food and nutritional security. She acknowledges that climate change threatens agriculture, food security, and peace, but emphasizes that “big problems allow for immense opportunity.”

Resilience became a common thread throughout the conference. Hassan Radoine, director of the School of Architecture and Design at UM6P, urges for a paradigm shift, explaining how most people perceive Africa as poor.

“What is resilience? The responsiveness to risk and inventing new solutions. The reconstructing of a community or a place, is resilience,” Radoine said.

Echoing this, Remy Sietchiping, UN-Habitat leader of regional and metropolitan planning, outlined the urban agenda of creating smart cities that encompass adaptability and most importantly, resilience.

“You cannot buy sustainability,” Randoine said.

During the last session of the conference, gears shifted towards the “smart chemistry” projects, which work closely with Moroccan company, OCP, the leading supplier of phosphate rock in the world. Paul M Cook Career Development Assistant Professor Yogeth Surendranath of the MIT Department of Chemistry presented on the natural resource, phosphorous, which is abundant to Morocco.

However, the process of creating phosphate products demands an incredible amount of energy. Surendranath’s research is targeted at elucidating the process of electrochemical phosphate reduction in molten salts, in order to lower economic and environmental costs, and advance Morocco in the chemical markets.

Henry Dreyfus Professor of Chemistry Christopher Cummins’ project is also working with phosphate, and has successfully created a new method for the synthesis of phosphorous. The method utilizes a “wet process,” which enables the reduction of energy inputs, waste, and overall harm to the environment.

Following Cummins, Professor Paul Barton of the Department of Chemistry, discussed his project on optimal industrial symbiosis for the Jorf Lasfar platform, the phosphate mineral processing facility in Morocco. Barton is studying ways to optimize the phosphate resource, to generate returns on investment while also being mindful of energy and water consumption.

Throughout the afternoon, goals for the future were at the forefront of everyone’s mind. UMRP aims to continue to conduct impactful research, tackle developmental challenges, and build a strong foundation for UM6P.

“This conference provided a wonderful platform for UMRP to showcase their projects, build a community with UM6P and other colleagues, and help the growing institutional commitment of MIT to engage fruitfully in a future of sustainable development for Africa,” said UMRP Executive Director Kurt Sternlof.

It was evident that the MIT faculty-led research is results-driven and exhibits a strong vision of a sustainable future. The idea that UMRP research projects develop small solutions to make big impacts, became a recurring element of the conference.

“Whether discussing urban metabolism, industrial symbiosis, chemical processing or the hydrological cycle, the common theme of recognizing and optimizing closed loops of resource use — circular economies of production, consumption and renewal — was clear and compelling, and therein beats the heart of sustainability,” Sternlof said.

Collaboration runs through J-WAFS-funded projects

by Andi Sutton | Abdul Latif Jameel Water and Food Systems Lab |

“In order to do the kind and scale of work that we do, international collaboration is essential. However, this can be difficult to fund,” Chris Voigt said. “J-WAFS is providing the support that we need for the cross-institutional and cross-sector collaboration that is enabling our work to move forward.”

Voigt, a professor in the MIT Department of Biological Engineering, made those comments at the first of two research workshops produced by the Abdul Latif Jameel Water and Food Systems Lab (J-WAFS) on Sept. 14th and Sept. 28th at the Samberg Center. The annual workshop brings members of the MIT community together to learn about the latest research results from J-WAFS-funded teams, to hear about newly funded projects, and to provide feedback on each other’s work.

The specific collaboration Voigt was referring to is a project that connects the work  on prokaryotic gene clusters in his lab to research at the Max Planck Institute of Molecular Plant Physiology in Germany and the Center for Plant Biotechnology and Genomics at the Universidad Politécnica in Spain.

Voigt and experts in plastid engineering and plant gene expression from these partnering institutions are working to engineer cereal grains to produce their own nitrogen, eliminating the need for added fertilizer. Their goal is to transform farming at every scale — reducing the greenhouse gas emissions of industrial fertilizer production as well as problems of eutrophication from nutrient run-off and reducing the cost of added nitrogen fertilizer. With a growing world population and increasing demand for grain as a food and fuel, the need for innovations in agricultural technologies is urgent, yet the technical challenges are steep and often require complementary areas of expertise. Therefore, when researchers like Voightshare their skills and resources with other global experts in pursuit of a shared goal, the combined effort has the potential to produce dramatic results.

The collaboration is a hallmark of MIT’s research culture. J-WAFS seeks to leverage that collaboration by being particularly welcoming of cross-disciplinary project proposals and research teams. In fact, the majority of J-WAFS current and concluding projects are led by two or more principal investigators, with many of those teams being cross-disciplinary.

In the case of a J-WAFS Solutions-funded project led by principal investigators Timothy Swager and Alexander Klibanov from the Department of Chemistry, interdisciplinary collaboration grew as the work on the project progressed. The team is developing a handheld food safety sensor that uses specialized droplets — called Janus emulsions — to test for bacterial contamination in food. The droplets behave like a dynamic lens, changing in the presence of specific bacteria.

In developing optical systems that can indicate the presence or absence of bacteria, including salmonella, by analyzing the light either transmitted through or emanating from these dynamic lenses, the researchers realized that they did not have the expertise to fully understand the optics they observed when the droplets were exposed to light. For that, they needed help. Swager reached out to Mathias Kolle, an assistant professor in the Department of Mechanical Engineering, whose expertise in optical materials proved to be key.

Kolle, who has received J-WAFS seed funding for his own work on industrial algae production, and his graduate student Sara Nagelberg provided the calculations necessary to understand the mechanics of light’s interaction with the particles. These insights contributed to sensor designs that were dramatically more effective, and the team has now launched a startup — Xibus Systems — and is currently working on product development.

“This is the beginning of a much longer story for us,” Swager commented, reflecting on his collaboration with Kolle’s lab.

Several other research teams are applying multiple disciplinary perspectives to their work.

In one project, Evelyn Wang, the Gail E. Kendall Professor in the Department of Mechanical Engineering, has teamed up with Mircea Dincă, an associate professor in the Department of Chemistry, to engineer highly absorbent metal organic frameworks in a device that pulls drinking water from air.

In another, assistant professor David Des Marais in the Department of Civil and Environmental Engineering is collaborating with Caroline Uhler, the Henry L. and Grace Doherty Assistant Professor in the Department of Electrical Engineering and Computer Science, to develop tools to analyze and understand the ways that genes regulate plants’ responses to environmental stressors such as drought. Their goal is to apply this understanding to better breed and engineer stress-tolerant plants so that crop yields can improve even as climate change creates more extreme growing conditions.

Meanwhile, J-WAFS itself collaborated with a partner program in organizing the event. The second day of the workshop coincided with the Tata Center’s annual research symposium, which was also held at the Samberg Center. J-WAFS and Tata’s missions have some significant overlaps — many Tata-funded MIT projects address food, water, and agriculture challenges in the developing world. The two groups merged audiences for their afternoon sessions and presentations to take advantage of these synergies, enabling participants of each event to interact and to learn about the food and water innovations that the programs are supporting.

By funding research in all schools at MIT and seeding and supporting innovative collaboration that crosses departments and schools alikeJ-WAFS seeks to advance research that can provide answers to what might be one of the most pressing questions of our time: How do we ensure safe and resilient supplies of water and food on our changing planet, now and in the future? When experts come together around an urgent question like this one, each one approaches it from a different angle. And when successes emerge from collaborations in J-WAFS-funded projects, it demonstrate sthe value of MIT’s culture of interdisciplinary collaboration.

Chemists discover unexpected enzyme structure

by Anne Trafton | MIT News Office |

Many microbes have an enzyme that can convert carbon dioxide to carbon monoxide. This reaction is critical for building carbon compounds and generating energy, particularly for bacteria that live in oxygen-free environments.

This enzyme is also of great interest to researchers who want to find new ways to remove greenhouse gases from the atmosphere and turn them into useful carbon-containing compounds. Current industrial methods for transforming carbon dioxide are very energy-intensive.

“There are industrial processes that do these reactions at high temperatures and high pressures, and then there’s this enzyme that can do the same thing at room temperature,” says Catherine Drennan, an MIT professor of chemistry and biology and a Howard Hughes Medical Institute Investigator. “For a long time, people have been interested in understanding how nature performs this challenging chemistry with this assembly of metals.”

Drennan and her colleagues at MIT, Brandeis University, and Aix-Marseille University in France have now discovered a unique aspect of the structure of the “C-cluster” — the collection of metal and sulfur atoms that forms the heart of the enzyme carbon monoxide dehydrogenase (CODH). Instead of forming a rigid scaffold, as had been expected, the cluster can actually change its configuration.

“It was not what we expected to see,” says Elizabeth Wittenborn, a recent MIT PhD recipient and the lead author of the study, which appears in the Oct. 2 issue of the journal eLife.

A molecular cartwheel

Metal-containing clusters such as the C-cluster perform many other critical reactions in microbes, including splitting nitrogen gas, that are difficult to replicate industrially.

Drennan began studying the structure of carbon monoxide dehydrogenase and the C-cluster about 20 years ago, soon after she started her lab at MIT. She and another research group each came up with a structure for the enzyme using X-ray crystallography, but the structures weren’t quite the same. The differences were eventually resolved and the structure of CODH was thought to be well-established.

Wittenborn took up the project a few years ago, in hopes of nailing down why the enzyme is so sensitive to inactivation by oxygen and determining how the C-cluster gets put together.

To the researchers’ surprise, their analysis revealed two distinct structures for the C-cluster. The first was an arrangement they had expected to see — a cube consisting of four sulfur atoms, three iron atoms, and a nickel atom, with a fourth iron atom connected to the cube.

In the second structure, however, the nickel atom is removed from the cube-like structure and takes the place of the fourth iron atom. The displaced iron atom binds to a nearby amino acid, cysteine, which holds it in its new location. One of the sulfur atoms also moves out of the cube. All of these movements appear to occur in unison, in a movement the researchers describe as a “molecular cartwheel.”

“The sulfur, the iron, and the nickel all move to new locations,” Drennan says. “We were really shocked. We thought we understood this enzyme, but we found it is doing this unbelievably dramatic movement that we never anticipated. Then we came up with more evidence that this is actually something that’s relevant and important — it’s not just a fluke thing but part of the design of this cluster.”

The researchers believe that this movement, which occurs upon oxygen exposure, helps to protect the cluster from completely and irreversibly falling apart in response to oxygen.

“It seems like this is a safety net, allowing the metals to get moved to locations where they’re more secure on the protein,” Drennan says.

Douglas Rees, a professor of chemistry at Caltech, described the paper as “a beautiful study of a fascinating cluster conversion process.”

“These clusters have mineral-like features and it might be thought they would be ‘as stable as a rock,’” says Rees, who was not involved in the research. “Instead, the clusters can be dynamic, which confers upon them properties that are critical to their function in a biological setting.”

Not a rigid scaffold

This is the largest metal shift that has ever been seen in any enzyme cluster, but smaller-scale rearrangements have been seen in some others, including a metal cluster found in the enzyme nitrogenase, which converts nitrogen gas to ammonia.

“In the past, people thought of these clusters as really being these rigid scaffolds, but just within the last few years there’s more and more evidence coming up that they’re not really rigid,” Drennan says.

The researchers are now trying to figure out how cells assemble these clusters. Learning more about how these clusters work, how they are assembled, and how they are affected by oxygen could help scientists who are trying to copy their action for industrial use, Drennan says. There is a great deal of interest in coming up with ways to combat greenhouse gas accumulation by, for example, converting carbon dioxide to carbon monoxide and then to acetate, which can be used as a building block for many kinds of useful carbon-containing compounds.

“It’s more complicated than people thought. If we understand it, then we have a much better chance of really mimicking the biological system,” Drennan says.

The research was funded by the National Institutes of Health and the French National Research Agency.

John M. Deutch endows new MIT Institute Professorship

by MIT News |

Institute Professor Emeritus John M. Deutch ’61, PhD ’65 has made a generous endowment gift to name an MIT Institute Professorship. This appointment — the highest honor awarded by MIT’s faculty and administration — recognizes faculty members who have “demonstrated exceptional distinction by a combination of leadership, accomplishment, and service in the scholarly, educational, and general intellectual life of the Institute or wider academic community.”  Currently, MIT has 10 active and 12 emeritus Institute Professors.

Deutch says his motivation for making the gift was his “great respect for MIT and for the tremendous professional and personal satisfaction I have enjoyed as a member of the MIT community for over 59 years.”

Deutch has earned distinction across a career spanning academia and government — including service on the chemistry faculties at Princeton University and MIT, in the MIT administration, and in the administrations of four U.S. presidents.

“It’s rare for anyone to possess the intellectual intensity, managerial rigor, and strategic vision to excel in scholarship, in academic leadership, and in national service; John Deutch is that rare individual,” says MIT President L. Rafael Reif. “Institute Professors are the keepers of the flame at MIT — those faculty members who in the eyes of their colleagues embody MIT’s highest ideals of scholarly achievement and service to the Institute and society. I find it wonderfully fitting that John has chosen to endow an Institute Professorship — an inspired act of creative citizenship.”

Deutch’s relationship with MIT began when he entered the three-two program in 1959. He holds a BA from Amherst College in history and economics and a BS in chemical engineering from MIT, awarded in 1961, as well as a PhD in physical chemistry from MIT, awarded in 1965. In 1966, after a year as a postdoc at the National Bureau of Standards, he joined the chemistry faculty at Princeton.

In 1970, Deutch returned to MIT to join the chemistry faculty, eventually serving as chair of the department from 1976 to 1977, dean of the School of Science from 1982 to 1985, and provost from 1985 to 1990. He was appointed an MIT Institute Professor in 1990, and in 2009 he received MIT’s Gordon Y Billard award “for special service of outstanding merit performed for the Institute.”

His career includes extensive government service: Director of Energy Research and Undersecretary of Energy in the Carter administration, a member of George H.W. Bush’s President’s Foreign Intelligence Advisory Board, as well as Undersecretary of Defense for Acquisitions and Technology, Deputy Secretary of Defense, and Director of Central Intelligence in the first Clinton administration.

He has served on many presidential and congressional commissions and advisory committees for government agencies and received numerous public service awards.

Deutch has been a board member and advisor to numerous corporations and a director or trustee of nonprofit organizations, including the Center for American Progress; the Council on Foreign Relations; Resources for the Future; Massachusetts General Hospital’s Physicians Organization; the Museum of Fine Arts, Boston; the Skolkovo Institute of Science and Technology; the Urban Institute; and Wellesley College.

Deutch was elected to the American Philosophical Society in 2007, and he delivered the 2010 Harvard University Godkin Lectures on the Essentials of Free Government and the Duties of the Citizen.

Deutch has more than 150 scientific publications, as well as numerous articles on technology, energy, international security, and public policy issues. He has supervised graduate students interested in chemistry, national security, and global energy issues. In recent years Deutch has participated in MIT interdisciplinary energy studies including the Future of Nuclear Energy, the Future of Coal (with a focus on carbon dioxide capture and sequestration), the Future of Natural Gas, and the Future of Solar Energy.

A big new home for the ultrasmall

by David L. Chandler |

Nanotechnology, the cutting-edge research field that explores ultrasmall materials, organisms, and devices, has now been graced with the largest, most sophisticated, and most accessible university research facility of its kind in the U.S.: It is the new $400 million MIT.nano building, which will have its official opening ceremonies next week.

The state-of-the-art facility includes two large floors of connected clean-room spaces that are open to view from the outside and available for use by an extraordinary number and variety of researchers across the Institute. It also features a whole floor of undergraduate chemistry teaching labs, and an ultrastable basement level dedicated to electron microscopes and other exquisitely sensitive imaging and measurement tools.

“In recent decades, we have gained the ability to see into the nanoscale with breathtaking precision. This insight has led to the development of tools and instruments that allow us to design and manipulate matter like nature does, atom by atom and molecule by molecule,” says Vladimir Bulović, the Fariborz Maseeh Professor in Emerging Technology and founding director of MIT.nano. “MIT.nano has arrived on campus at the dawn of the Nano Age. In the decades ahead, its open-access facilities for nanoscience and nanoengineering will equip our community with instruments and processes that can further harness the power of nanotechnology in service to humanity’s greatest challenges.”

“In terms of vibrations and electromagnetic noise, MIT.nano may be the quietest space on campus. But in a community where more than half of recently tenured faculty do work at the nanoscale, MIT.nano’s superb shared facilities guarantee that it will become a lively center of community and collaboration, says MIT President L. Rafael Reif. “I am grateful to the exceptional team — including Provost Martin Schmidt, Founding Director Vladimir Bulovic, and many others — that delivered this extraordinarily sophisticated building on an extraordinarily inaccessible construction site, making a better MIT so we can help to make a better world.”

Accessible and flexible

The 214,000-square-foot building, with its soaring glass facades, sophisticated design and instrumentation, and powerful air-exchange systems, lies at the heart of campus and just off the Infinite Corridor. It took shape during six years of design and construction, and was delivered exactly on schedule and on budget, a rare achievement for such a massive and technologically complex construction project.

“MIT.nano is a game-changer for the MIT research enterprise,” says Vice President for Research Maria Zuber. “It will provide measurement and imaging capabilities that will dramatically advance science and technology in disciplines across the Institute.”

At the heart of the building are two levels of clean rooms — research environments in which the air is continuously scrubbed and replaced to maintain a standard that allows no more than 100 particles of  0.5 microns or larger within a cubic foot of air. To achieve such cleanliness, work on the building has included strict filtration measures and access restrictions for more than a year, and at the moment, with the spaces not yet in full use, they far exceed that standard.

All of the lab and instrumentation spaces in the building will be used as shared facilities, accessible to any MIT researcher who needs the specialized tools that will be installed there over the coming months and years. The tools will be continually upgraded, as the building is designed to be flexible and ready for the latest advances in equipment for making, studying, measuring, and manipulating nanoscale objects — things measured in billionths of a meter, whether they be technological, biological, or chemical.

Many of the tools and instruments to be installed in MIT.nano are so costly and require so much support in services and operations that they would likely be out of reach for a single researcher or team. One of the instruments now installed and being calibrated in the basement imaging and metrology suites — sitting atop a 5-million-pound slab of concrete to provide the steadiest base possible — is a cryogenic transmission electron microscope. This multimillion dollar instrument is hosted in an equally costly room with fine-tuned control of temperature and humidity, specialized features to minimize the mechanical and electromagnetic interference, and a technical support team. The device, one of two currently being installed in MIT.nano, will enable detailed 3-D observations of cells or materials held at very low liquid-nitrogen temperatures, giving a glimpse into the exquisite nanoscale features of the soft-matter world.

Almost half of the MIT.nano’s footage is devoted to lab space — 100,000 square feet of it — which is about 100 times larger in size than the typical private lab space of a young experimental research group at MIT, Bulović says. Private labs typically take a few years to build out, and once in place often house valuable equipment that is idle for at least part of the time. It will similarly take a few years to fully build out MIT.nano’s shared labs, but Bulović expects that the growing collection of advanced instruments will rarely be idle. The instrument sets will be selected and designed to drastically improve a researcher’s ability to hit the ground running with access to the best tools from the start, he says.

Principal investigators often “find there’s a benefit to contributing tools to the community so they can be shared and perfected through their use,” Bulović says. “They recognize that as these tools are not needed for their own work 24/7, attracting additional instrument users can generate a revenue stream for the tool, which supports maintenance and future upgrades while also enhancing the research output of labs that would not have access to those tools otherwise.”

A facility sized to meet demand

Once MIT.nano is fully outfitted, over 2,000 MIT faculty and researchers are expected to use the new facilities every year, according to Bulović. Besides its clean-room floors, instrumentation floor, chemistry labs, and the top-floor prototyping labs, the new building also houses a unique facility at MIT: a two-story virtual-reality and visualization space called the Immersion Lab. It could be used by researchers studying subcellular-resolution images of biological tissues or complex computer simulations, or planetary scientists walking through a reproduced Martian surface looking for geologically interesting sites; it may even lend itself to artistic creations or performances, he says. “It’s a unique space. The beauty of it is it will connect to the huge datasets” coming from instruments such as the cryoelectron microscopes, or from simulations generated by artificial intelligence labs, or from other external datasets.

The chemistry labs on the building’s fifth floor, which can accommodate a dozen classes of a dozen students each, are already fully outfitted and in full use for this fall. The labs allow undergraduate chemistry students an exceptionally full and up-to-date experience of lab processes and tools.

“The Department of Chemistry is delighted to move into our new state-of-the-art Undergraduate Teaching Laboratories (UGTL) in MIT.nano,” says department head Timothy Jamison. “The synergy between our URIECA curriculum and this new space enables us to provide an even stronger educational foundation in experimental chemistry to our students. Vladimir Bulović and the MIT.nano team have been wonderful partners at all stages — throughout the design, construction, and move — and we look forward to other opportunities resulting from this collaboration and the presence of our UGTL in MIT.nano.”

The building itself was designed to be far more open and accessible than any comparable clean-room facility in the world. Those outside the labs can watch through MIT.nano’s many windows and see the use of these specialized devices and how such labs work. Meanwhile, researchers themselves can more easily interact with each other and see the sunshine and the gently waving bamboo plants outdoors as a reminder of the outside world that they are working to benefit.

A courtyard path on the south side of the building is named the Improbability Walk, in honor of the late MIT Institute Professor Emerita Mildred “Millie” Dresselhaus. The name is a nod to a statement by the beloved mentor, collaborator, teacher, and world-renowned pioneer in solid-state physics and nanoscale engineering, who once said, “My background is so improbable — that I’d be here from where I started.”

Those who walk through the building’s sunlight-soaked corridors and galleries will notice walls surfaced with panels of limestone from the Yangtze Platform of southwestern China. The limestone’s delicate patterns of fine horizontal lines are made up of tiny microparticles, such as bits of ancient microorganisms, laid down at the bottom of primeval waters before dinosaurs roamed the Earth. The very newest marvels to emerge in nanotechnology will thus be coming into existence right within view of some of their most ancient minuscule precursors.

Plug-and-play technology automates chemical synthesis

by Anne Trafton |

Designing a new chemical synthesis can be a laborious process with a fair amount of drudgery involved — mixing chemicals, measuring temperatures, analyzing the results, then starting over again if it doesn’t work out.

MIT researchers have now developed an automated chemical synthesis system that can take over many of the more tedious aspects of chemical experimentation, freeing up chemists to spend more time on the more analytical and creative aspects of their research.

“Our goal was to create an easy-to-use system that would allow scientists to come up with the best conditions for making their molecules of interest — a general chemical synthesis platform with as much flexibility as possible,” says Timothy F. Jamison, head of MIT’s Department of Chemistry and one of the leaders of the research team.

This system could cut the amount of time required to optimize a new reaction, from weeks or months down to a single day, the researchers say. They have patented the technology and hope that it will be widely used in both academic and industrial chemistry labs.

“When we set out to do this, we wanted it to be something that was generally usable in the lab and not too expensive,” says Klavs F. Jensen, the Warren K. Lewis Professor of Chemical Engineering at MIT, who co-led the research team. “We wanted to develop technology that would make it much easier for chemists to develop new reactions.”

Former MIT postdoc Anne-Catherine Bédard and former MIT research associate Andrea Adamo are the lead authors of the paper, which appears in the Sept. 20 online edition of Science.

Going with the flow

The new system makes use of a type of chemical synthesis known as continuous flow. With this approach, the chemical reagents flow through a series of tubes, and new chemicals can be added at different points. Other processes such as separation can also occur as the chemicals flow through the system.

In contrast, traditional “batch chemistry” requires performing each step separately, and human intervention is required to move the reagents along to the next step.

A few years ago, Jensen and Jamison developed a continuous flow system that can rapidly produce pharmaceuticals on demand. They then turned their attention to smaller-scale systems that could be used in research labs, in hopes of eliminating much of the repetitive manual experimentation needed to develop a new process to synthesize a particular molecule.

To achieve that, the team designed a plug-and-play system with several different modules that can be combined to perform different types of synthesis. Each module is about the size of a large cell phone and can be plugged into a port, just as computer components can be connected via USB ports. Some of modules perform specific reactions, such as those catalyzed by light or by a solid catalyst, while others separate out the desired products. In the current system, five of these components can be connected at once.

The person using the machine comes up with a plan for how to synthesize a desired molecule and then plugs in the necessary modules. The user then tells the machine what reaction conditions (temperature, concentration of reagents, flow rate, etc.) to start with. For the next day or so, the machine uses a general optimization program to explore different conditions and ultimately to determine which conditions generate the highest yield of the desired product.

Meanwhile, instead of manually mixing chemicals together and then isolating and testing the products, the researcher can go off to do something else.

“While the optimizations are being performed, the users could be talking to their colleagues about other ideas, they could be working on manuscripts, or they could be analyzing data from previous runs. In other words, doing the more human aspects of research,” Jamison says.

Rapid testing

In the new study, the researchers created about 50 different organic compounds, and they believe the technology could help scientists more rapidly design and produce compounds that could be tested as potential drugs or other useful products. This system should also make it easier for chemists to reproduce reactions that others have developed, without having to reoptimize every step of the synthesis.

“If you have a machine where you just plug in the components, and someone tries to do the same synthesis with a similar machine, they ought to be able to get the same results,” Jensen says.

The researchers are now working on a new version of the technology that could take over even more of the design work, including coming up with the order and type of modules to be used.

The research was funded by the Defense Advanced Research Projects Agency (DARPA).