New ENG Prof Expert on Tissue Engineering
By Amy Laskowski, BU Today
It’s estimated that 18 Americans die every day waiting for an organ donation. More than 120,000 are currently on a waiting list. And even if a patient receives that desperately needed kidney or liver, there is still a 10 percent to 20 percent chance that the new organ will fail. So researchers in the areas of tissue engineering and regenerative medicine are actively pursuing ways to use a patient’s own cells to grow an organ, which would eliminate the need for donors and the risk of organ rejection.
Enter Christopher Chen, a new College of Engineering professor of biomedical engineering, who is one of the world’s leading experts on regenerative medicine. Chen studies tissue engineering and mechanobiology, which combines engineering and biology to study how physical forces and changes in cell or tissue mechanics affect development, physiology, and disease.
“Since most diseases involve the loss or damage of one tissue or organ, being able to fix that one thing, for someone who is otherwise healthy, could have a dramatic impact on their quality of life,” says Chen, who came to Boston University from the University of Pennsylvania in August and is still unpacking at his Cummington Street office. “If we can understand the basic mechanisms of how tissues and cells regenerate, it could give us tools to broadly extend people’s lives. Figuring out how to ‘manufacture’ such things is important.”
Chen says he has always been interested in trying to understand why normal cells go awry. As a PhD student at the Harvard-MIT Division of Health Sciences and Technology, Chen began to wonder about cells’ unfavorable responses, like degeneration, scar formation, and organ rejection. He thought that if he could better understand these responses and why they were occurring, he would be able to more effectively find solutions.
In his new lab at BU, Chen and his team of students are creating artificial environments populated by cells, like miniature vivariums, where they can observe and identify the underlying mechanisms that cause cells to interact with materials and to build tissues. Understanding how cells behave allows researchers to better understand the biology of stem cells, vascularization (the growth of veins in tissue), and cancer, and could ultimately help them to engineer artificial tissues and build hybrid biological-artificial medical devices.
“If we could guide cells to do the types of things we want them to, and if we understand how they make those decisions, then we might be able to artificially turn on and off the switches that make them go down a certain pathway,” Chen says.
“Maybe that’s guiding a stem cell to become a cardiac cell, or preventing a fibroblast to not form a scar.”
Another key aspect of Chen’s research involves using a 3-D “printer” to help create organs using a patient’s own cells. Until recently, a researcher could make a 2-D structure out of various types of tissue, but couldn’t replicate a larger organ’s 3-D dimensions. Why? “When an organ gets beyond a certain size, the cells in the middle can’t get oxygen and so they suffocate and die,” Chen says. “So we are working to use 3-D printers to build blood vessels to feed the cells in the middle, like what happens in our body.”
To build these artificial blood vessel networks, Chen and colleagues at Penn and MIT devised a system using sugar to create a freestanding 3-D network that sits inside a mold. Once the network hardens, the lines of sugar are surrounded with a gel made up of cells from the organ that needs replacing. When the sugar dissolves, it leaves behind a clump of the organ’s cells with a network of hollow channels, which can then be lined with other cells to create blood vessels, allowing the kidney or liver cells to receive nutrients and oxygen in much the same way they would if they were in the body. This past week, Chen’s 3-D printing breakthrough was highlighted in James Woods’ new show, Futurescape, on the Science Channel. (The episode, titled “Living Forever,” is scheduled to air several times this week.) This kind of platform technology, while quick and inexpensive, is years from producing artificial organs on the scale needed for humans.
Chen’s research has already earned him numerous accolades. He is the recipient of a Presidential Early Career Award for Scientists and Engineers, an Office of Naval Research Young Investigator Award, the Herbert W. Dickerman Award for Outstanding Contribution to Science, and several other honors. He is a fellow of the American Institute for Medical and Biological Engineering and an editor of the Journal of Cell Science. Chen is the founding director of the University of Pennsylvania’s Center for Engineering Cells and Regeneration. He earned a bachelor’s at Harvard, a master’s at MIT, a PhD from the Harvard-MIT Division of Health Sciences and Technology, and an MD from Harvard Medical School.
“Chris Chen is an extraordinary scientist and will provide senior leadership and mentoring to advance our world-class biomedical engineering department,” says Kenneth R. Lutchen, dean of ENG. “He immediately amplifies and reinforces BU’s leadership position in bioengineering. Moreover, Dr. Chen is highly respected as a person and as an educator. He is one of the most well-liked colleagues in his field.”
Chen says he anticipates that his research involving 3-D printers to create blood vessel networks could be the kind of project to be developed at ENG’s new Engineering Product Innovation Center (EPIC) and that he is eager to share this technique with students. When it opens in January, the 20,000-square-foot teaching and design studio will be equipped with the latest industry technology, such as a computer-aided design studio, demonstration areas, fabrication facilities, materials testing, and 3-D printers.
“I love how students come in with a fresh perspective and are always asking questions,” says Chen. “Sometimes the most basic question can really jolt you into reframing what you’re working on, and open new avenues for research. If you’ve been in your field for a long time, you tend to not notice the things that don’t fit. I think having that fresh look is why the research and educational missions of a university are so synergistic, and of course what keeps us aging professors all young at heart.”
Tomorrow, December 5, Christopher Chen will be one of the speakers at the 17th annual BU Photonics Center Symposium. The event is free and open to the public. Find registration and more information here.
Goldberg, Wong named to coordinate teaching, recruitment
By Susan Seligson, BU Today
It’s a fitting acronym: STEM is the basis for budding careers, for the growing of cutting-edge research, and for increased competence across a range of disciplines. While Boston University has long shown a strong commitment to education in STEM fields—science, technology, engineering, and mathematics—it has recently launched an initiative to improve that commitment by boosting interdisciplinary cooperation, recruiting more students in underrepresented populations, and arming the University with even more of a competitive edge in seeking outside funding.
Jean Morrison, University provost and chief academic officer, recently named two BU faculty members to take STEM to the next level. Bennett Goldberg, a College of Arts & Sciences professor of physics and a College of Engineering professor of electrical and computer engineering, and of biomedical engineering, has been appointed director of BU’s STEM Education Initiatives. Joyce Y. Wong, an ENG professor of biomedical engineering and of materials science and engineering, has been named director of a new University effort to advance women in STEM fields.
Goldberg will be responsible for oversight and coordination of efforts to “increase effectiveness of instruction” in STEM subjects, says Morrison in announcing the appointment. “A world-class scientist, innovator, and teacher, who has devoted his career to impactful interdisciplinary scholarship, Professor Goldberg is exceptionally equipped for this responsibility,” she says. The new post includes four major areas of oversight: leading an effort to “articulate the aspirations” of BU faculty for undergraduate STEM education; working with schools and colleges and the Center for Excellence and Innovation in Teaching to advance the “sharing of best practices”; working to boost recruitment of students, including women and minorities, underrepresented in STEM programs; and directing the development, writing, and submission of grants supporting STEM education at the University.
“STEM education at BU has a fair amount of innovation, but we don’t have a really coordinated effort or strategic plan,” says Goldberg. “If you look at what’s happening in higher education in the United States, there are a lot of pressures, and our model for the future must include high-engagement learning—moving away from the traditional talking head at the front of the class.” In STEM education in particular, the talking head model reaches “a very small fraction of our students,” he says.
STEM education at BU is already embracing this move away from the traditional lecture model, but Goldberg will coordinate the establishment of more interactive learning studios, more peer learning, more small seminars like those used in some engineering courses, and more roundtable teaching. “My job is really to figure out what kind of support is necessary and how we can create a collective vision,” he says. “It’s planning, it’s discussing, it’s developing, and it’s implementing.”
Goldberg, who was named BU’s 2013 United Methodist Scholar-Teacher of the Year, has long held an active interest in improving education in math and the sciences. Director of the Center for Nanoscience and Nanobiotechnology since 2004, he earned a bachelor’s from Harvard University and a master’s and a doctorate from Brown University. Of Goldberg’s work cultivating clean energy sources, developing new drug delivery systems, and diagnostic methods, Morrison says that he “has committed himself to breaking boundaries, working across fields of scientific research in a way that pushes the limits of our capabilities.”
Wong is “uniquely positioned to help BU emerge as a leader in addressing the underrepresentation of women” in STEM fields, according to Morrison. She notes that while BU attracts outstanding female students and faculty in these fields, “there is more work to be done both in recruitment and retention and in our endeavors to support their success.” Wong’s undergraduate and doctoral degrees are from the Massachusetts Institute of Technology. Her research focuses on the development of biological materials that could aid in detecting cancer and cardiovascular disease.
“I look forward to engaging all members of the BU community and to reaching out to the many people on campus who are running excellent programs at all levels, precollege, undergraduate, graduate, postdoctoral, and faculty, to advance STEM in an equitable manner,” says Wong.
Students Develop Nanoscale Structures to Probe Neurons
By Mark Dwortzan
In November a group of five undergraduates became the first Boston University team to participate in BIOMOD, an international student biomolecular design competition focused on the systematic assembly of biological molecules into complex nanoscale machines that can perform useful tasks. Having designed and implemented their project over the summer, they presented it to a panel of judges at the Wyss Institute for Biologically Inspired Engineering at Harvard in November at BIOMOD’s annual Jamboree, and emerged as one of 13 gold winners.
Competitors included many top-tier colleges and universities across the globe, from Columbia University to the Tokyo Institute of Technology, advancing biomolecular devices capable of everything from fighting cancer to detecting the presence of pathogens.
The BU team, Terriergami, sought to design a novel approach to fabricate DNA origami, or nanoscale objects made of folded DNA, to reach brain cells in an efficient manner. To achieve their goal, the students systematically folded DNA into barrel-shaped structures, attaching a peptide to the surface of the barrel to improve brain cell targeting capability.
Terriergami’s nanoscale objects could be developed to sense a neuron’s cellular environment or deliver drugs directly to it, and ultimately enable clinicians to diagnose or treat brain disorders.
“To my knowledge, this is one of the first proof-of-principle demonstrations of delivering DNA origami to neurons,” said Assistant Professor Xue Han(BME), who worked with these students in her lab. “The team did a great job presenting their research and representing the College of Engineering and BU.”
Supervised by Han and BME postdoctoral fellow Richie Kohman, the team includes three BME seniors, Prakash Iyer (also majoring in Neuroscience), Aditya Sengupta and Harvin Vallabhaneni; one junior, Steve Man (Computer Science); and one BME sophomore, Sangeeta Satish. The undergraduates joined the team eager to explore DNA origami and its applications, and came away with new skills and insights.
“Over the summer we used DNA as building blocks and self-assembly methods to create tiny delivery ‘cages’ out of the DNA,” said Vallabhaneni. “These were all concepts I studied in introductory courses. Through BIOMOD, I was expected not only to understand these concepts, but also to apply them to solve problems.”
“I was drawn by the idea that we could use the body’s own materials, its DNA, in order to target and possibly treat diseases,” said Man. “There is a large focus in medicine on ensuring that the body’s own immune system doesn’t reject treatments. Disguising these medical compounds underneath the human body’s own biology is an elegant and practical way of overcoming this obstacle.”
Building on their BIOMOD work, the BME seniors on the team will further explore the use of DNA origami in neurons in Han’s lab as part of their senior design project.
The BU team’s project was funded through the College of Engineering, BME Department and BU’s Peter Paul Fellowship.
For more information, please see video.
Advances New Approach to Preventing Spread and Use of Substandard Medicine
By Mark Dwortzan
An estimated 20 percent to 50 percent of medicines distributed in developing countries are either counterfeit or significantly substandard, resulting in thousands of preventable medical complications and deaths. To address this problem, Associate Professor Muhammad Zaman(BME, MSE) has spent the past two years developing PharmaCheck, a fast, portable, user-friendly detector for screening counterfeit and substandard anti-malarials, antibiotics and other essential medicines.
Scientific American was so impressed with PharmaCheck and its potential to improve people’s lives that the magazine featured the concept behind it—a new approach to preventing the spread and use of substandard medicine—as one of “Ten World Changing Ideas” in its annual roundup article on proven, scalable innovations that could dramatically impact society in the near future. Appearing in the December issue along with innovations ranging from planes that snap together to smartphones as thin as a credit card, the article lauds PharmaCheck as an outstanding example of microfluidic, lab-on-a-chip technology.
“I am really honored and excited by this recognition,” said Zaman. “Our funding partners have been amazingly supportive of our high-risk approach, and we hope that this recognition and their ongoing support will enable our team to help make the world a better and a safer place for all those who battle deadly diseases.”
PharmaCheck—developed by Zaman and graduate students Darash Desai (BME), Nga Ho (BME), Andrea Fernandes (SMG, SPH) and research scientist Atena Shemiran (BME)—is simple to operate. The user places a pill into a small testing box which instantly reports the amount of active ingredient found in the pill. The team’s ultimate goal is to enable users from pharmacists to regulatory authorities to effectively and easily control the quality of medicine delivered to patients. Toward that end, Zaman and his collaborators are now pursuing a series of field studies to test PharmaCheck’s performance on anti-malarials, antibiotics, uterotonics (used to induce labor) and medications targeting tuberculosis and HIV.
The device’s clear potential to dramatically improve health outcomes in resource-limited countries has attracted significant funding over the past two years from the US Pharmacopeial (USP) Convention under the Promoting the Quality of Medicines (PQM) program funded by USAID. USP has provided financial support to complete a prototype and conduct extensive field studies in Ghana through its Center for Pharmaceutical Quality Research Center. PharmaCheck has received additional funding from Saving Lives at Birth, the Coulter Foundation, the Center for Integration of Medicine and Innovative Technology, and the National Collegiate Inventors and Innovators Alliance (NCIIA).
More information about PharmaCheck, including a video presentation, is available here.
By Mark Dwortzan
In a ceremony held October 25 at the Boston University Photonics Center, the College of Engineering celebrated its alumni and announced the 2013 Distinguished Alumni Awards. Presented by Dean Kenneth R. Lutchen following a buffet dinner and champagne toast, the awards recognize individuals who have made significant contributions to their alma mater, community and profession. Lutchen commended the recipients for bringing honor to the College through their careers, commitment to the highest standards of excellence, and devotion to the College.
Anton Papp (EE’90), vice president for Corporate Development at Teradata, received the Service to Alma Mater award, which honors alumni who have enhanced the College of Engineering’s stature through voluntary service to BU.
At Teradata Papp oversees, evaluates and executes investments, mergers and acquisitions, and strategy. Prior to joining Teradata, he served as vice president of Corporate Development & Global Alliances at Aprimo and held numerous investment banking positions. A graduate of the prestigious US Navy Fighter Weapons School (TOPGUN), Papp attended BU on a Naval ROTC scholarship and served as a Naval Officer and F-14 Tomcat Flight Instructor. He also earned an MBA in Finance from Columbia Business School.
Papp serves on the College of Engineering Dean’s Advisory Board, the ENG West Coast Alumni Leadership Council, and the BU West Coast Regional Campaign Committee. He has been the leading supporter for the ENG/SMG Summer Leadership Institute program, and part of the College’s efforts to recruit top undergraduates.
Dan Ryan and Aaron Ganick (both ECE’10), cofounders of the telecommunications companyByteLight, received the Distinguished Young Alumni award, which honors outstanding alumni within 10 years of graduation for outstanding service to their profession or community.
A startup that emerged out of the Smart Lighting Engineering Research Center at BU, ByteLight has produced a system that’s similar to an indoor GPS. Special LED lights provided by Bytelight enable your smartphone to determine your location and to bring up location-based information ranging from store coupons to museum exhibit descriptions.
George Savage (BME’81), Chief Medical Officer and cofounder of Proteus Digital Health, and a member of the BU College of Engineering West Coast Advisory Council, received the Service to the Profession award, which honors alumni whose work has significantly contributed to the advancement of their profession and brought them recognition within their field.
Savage has started 10 companies since 1989 as entrepreneur or founding investor, including FemRx (acquired by Johnson and Johnson), CardioRhythm (acquired by Medtronic) and QRx Pharmaceuticals. He holds an M.D. from Tufts University School of Medicine and an M.B.A. from Stanford University Graduate School of Business, and serves on the boards of Menlo Healthcare Ministry, the Pacific Research Institute and Silent Cal Productions.
At Proteus, Savage has advanced a system of small, ingestible event markers that are implanted in a patient’s medications. A monitor worn as a patch on the patient identifies each pill upon swallowing and tracks vital signs, which are uploaded to the patient’s mobile phone and transmitted to caregivers and healthcare professionals. The system allows for instantaneous and personalized treatment and promises to transform the way doctors monitor patients’ medicine.
NSF Research Program Helps ENG Vets Shape Careers
By Mark Dwortzan
US military personnel return from active duty with highly marketable knowledge and skills, but many find it difficult to quickly parlay their experience into well-paying jobs. To help rectify the situation, the National Science Foundation (NSF) funds the Veteran’s Research Supplement (VRS) program, which allows veterans at selected colleges and universities to participate in industrially relevant research in science, technology, engineering, and mathematics (STEM)—fields in which job openings far outpace the supply of qualified US applicants.
Since the inception of VRS in 2011, the College of Engineering’s NSF Industry/University Collaborative Research Center for Biophotonic Sensors & Systems has welcomed the opportunity to engage veterans in research through this program.
“Vets come to us with an unusually strong work ethic and high confidence but often lack the experience to be comfortable in taking on a big research project,” said BU Photonics CenterDirector and Professor Thomas Bifano (ME, MSE). “VRS gives them the opportunity to take on such projects and pursue careers in research, which is the main engine of our economy.”
So far two veterans have thrived in faculty-supervised summer projects funded by VRS, emerging not only with new research skills but also a more well-defined career path.
Cliff Chan: From Technician to Engineer
Cliff Chan, who deployed four times in the Middle East and Southeast Asia as an Air Force Guidance and Control Specialist, came to BU seeking to take his skillset to the next level. With a B.S. in mathematics and computer science from the University of California, San Diego, two years developing software for an electronic health records company, and four years maintaining aircraft control systems for the Air Force under his belt, Chan aspired to learn how to design the kinds of technologies he came across during his military service.
To transform himself from a technician to an engineer, he sought a way to earn a master’s degree in electrical engineering in a reasonable timeframe without having to start from scratch, and he found it in the College of Engineering’s Late Entry Accelerated Program (LEAP). Like all LEAP students, Chan spent his first year taking undergraduate engineering courses to get up to speed, but got his first taste of engineering design the following summer (2011), thanks to the VRS program. Working for three months in Professor Jerome Mertz’s (BME) Biomicroscopy Lab within BU’s Center for Biophotonic Sensors and Systems, he developed software that enables microscopes to provide high-contrast images of biological samples in real time.
“The project was a real transition for me, as I had to solve a problem by first figuring out what I needed to learn, and then how to apply it,” recalled Chan, who was used to getting more explicit instructions in the Air Force and had never worked in a research lab. “It opened up my eyes to another world.”
Subsequently hired to work full-time in the Biomicroscopy Lab while completing his Master of Engineering in electrical engineering, Chan has continued to advance microscopy techniques aimed at improving medical diagnostic imaging. The experience has led him to consider working in research and development for defense and other industries, conducting experiments and designing devices with real-world application.
It has also prepared him to work through the inevitable unexpected challenges that arise in advancing new technologies.
“What I like about Cliff is that he’s undaunted,” said Mertz. “He wants to learn everything that’s out there to tackle his work. The problems we faced were much more complex than I had anticipated, but Cliff’s efforts definitely kept us on track, and kept us progressing.”
Chris Stockbridge: From Defusing Roadside Bombs to Protecting Future Soldiers
Chris Stockbridge returned to civilian life after five years as an officer and combat engineer in the Army that included two tours of duty in Iraq. During each deployment he came to appreciate the engineering behind technologies used to protect soldiers, including devices used to search for and destroy roadside bombs. Equipped with those experiences and a B.S. in mechanical engineering from the US Military Academy at West Point, he applied to the PhD program in mechanical engineering at BU with the goal of working as a civilian engineer at a national military research lab.
“I came to BU to study micro-electro-mechanical systems (MEMS), particularly those which could be of great value in military applications, and because I knew that the Photonics Center has a strong relationship with the US Army Research Laboratory,” said Stockbridge.
Supported last summer by the VRS program to serve as the lead student in an NSF-funded project in Bifano’s Precision Optics Research Lab, he began fabricating MEMS for a new deformable mirror design for use in the Keck and other very large telescopes. Aimed at supplying the telescopes with mirrors that have more pixels for finer imaging control, his work could enable astronomers to make observations that shed light on the origin of the universe and the existence of life on extra-solar planets.
“The primary benefit to me from this project was spending more time doing hands-on MEMS fabrication work,” said Stockbridge, who had already spent two years working on the design of deformable mirrors in Bifano’s lab. “While I would prefer to work more in design after graduation, the hands-on skills are important for getting an appreciation of each process step that goes into building a MEMS mirror.”
As he has cultivated those skills, Stockbridge has proven to be an invaluable asset in Bifano’s lab.
“Chris is a consummate engineer who seems to thrive on tackling problems that are both thorny and hard, and I can see in his work the experience and training that he gained while serving in the Army,” said Bifano. “He is a natural collaborator, and all of the other students in my lab and in the labs of my close colleagues have come to rely on him for his strong sense of mechanical design and for his eagerness to help those around him. Chris will make a great professional engineer.”
By Mark Dwortzan
Peace Islands Institute (PII), a northeastern-US-based think tank promoting education, friendship and harmony among peoples of diverse backgrounds, has named Associate ProfessorMuhammad Zaman (BME, MSE) as the recipient of its 2013 Global Education Award.
PII selected Zaman for the award in recognition of “his research on developing computational and experimental tools to improve the quality of life, education and the practice of medicine in the developing world,” said Burhan Kaya, director of PII’s Center for Global Affairs.
The organization will present the award to Zaman at its fifth annual Friendship & Awards Dinner on November 13 at Four Seasons Boston Hotel.
“I am absolutely thrilled and honored to receive this award, which reflects a collective effort of my students, researchers and colleagues around the world,” said Zaman. “I am deeply grateful to the Peace Island Institute for recognizing our work in global education and our efforts to improve access and the quality of learning and instruction in some of the most impoverished parts of the world.”
Last year’s recipients of PII awards include Sherman Teichman, founding director or the Institute for Global Leadership (Global Education Award); Michael Rich, MD, director of the Center on Media and Child Health at Boston Children’s Hospital (Media Award); and Congressman Bill Keating (Legislative Award).
A BU faculty member since 2009, Zaman heads the Cellular and Molecular Dynamics Lab, which engineers new experimental and computational technologies for major healthcare problems in both the developing and developed world, including probing the mechanisms of cancer metastasis. Meanwhile, Zaman is developing robust, cheap, portable and user-friendly diagnostics and analysis toolkits to address global health challenges.
As director of the Laboratory for Engineering Education and Development (LEED), he works with BU students to advance technologies to detect counterfeit drugs, preserve biological reagents used in diagnostic tests and provide other in-demand healthcare solutions targeting the specific needs of resource-limited countries. He is also co-director of the Africa Biomedical Engineering Initiative, which was funded by UN Economic Commission for Africa to improve biomedical engineering education, innovation and practice in Africa.
Zaman’s achievements in cancer and global health research have earned him funding from USAID, the Saving Lives at Birth Consortium, U.S. Pharmacopeial Convention, the National Institutes of Health, the National Science Foundation and many private foundations, as well as several invitations to participate in U.S. National Academy of Engineering research and education symposia. Zaman has also served as keynote or plenary speaker at major national and international conferences and published dozens of highly-cited papers in leading biomedical journals.
New Laser Technique Boosts Accuracy of DNA Sequencing Method
By Mark Dwortzan
Low-cost, ultra-fast DNA sequencing would revolutionize healthcare and biomedical research, sparking major advances in drug development, preventative medicine and personalized medicine. By gaining access to the entire sequence of your genome, a physician could determine the probability that you’ll develop a specific genetic disease or tolerate selected medications. In pursuit of that goal, Associate Professor Amit Meller (BME, MSE) has spent much of the past decade spearheading a method that uses solid state nanopores—two-to-five-nanometer-wide holes in silicon chips that read DNA strands as they pass through—to optically sequence the four nucleotides (A, C, G, T) encoding each DNA molecule.
Now Meller and a team of researchers at Boston University—Professor Theodore Moustakas (ECE, MSE) and research assistants Nicolas Di Fiori (Physics, PhD’13) and Allison Squires (BME, PhD’14)—and Technion-Israel Institute of Technology—have discovered a simple way to improve the sensitivity, accuracy and speed of the method, making it an even more viable option for DNA sequencing or characterization of small proteins.
In the November 3 online edition of Nature Nanotechnology, the team demonstrated that focusing a low-power, commercially available green laser on a nanopore increases current near walls of the pore, which is immersed in salt water. As the current increases, it sweeps the salt water along with it in the opposite direction of incoming samples. The onrushing water, in turn, acts as a brake, slowing down the passage of DNA through the pore. As a result, nanoscale sensors in the pore can get a higher-resolution read of each nucleotide as it crosses the pore, and identify small proteins in their native state that could not previously be detected.
“The light-induced phenomenon that we describe in this paper can be used to switch on and off the ‘brakes’ acting on individual biopolymers, such as DNA or proteins sliding through the nanopores, in real time,” Meller explained. “This critically enhances the sensing resolution of solid-state nanopores, and can be easily integrated in future nanopore-based DNA sequencing and protein detection technologies.”
Slowing down DNA is essential to DNA or RNA sequencing with nanopores, so that nanoscale sensors, like sports referees, can make the right call on what’s passing through.
“The goal is to hold a base pair of DNA nucleotides in the nanopore’s sensing volume long enough to ‘call the base’ (i.e, determine if it’s an A, C, G or T),” said Squires, who fabricated nanopores and ran experiments in the study. “The signal needs to be sufficiently different for each base for sensors in the nanopore to make the call. If the sample proceeds through the sensing volume too quickly, it’s hard for the sensors to interpret the signal and make the right call.”
Other methods designed to slow down DNA in nanopores change the sensing properties of the pore, making it more difficult to ensure accuracy of detected base pairs. Shining laser light on the nanopore alters only the local surface charge, an effect that’s completely reversible within milliseconds by switching the laser off.
As an added bonus, the researchers found that the sudden increase in surface charge and resulting flow of water reliably unblocks clogged nanopores, which can take a long time to clean, significantly extending their lifetime.
Meller and his team characterized the amount of increase in current under varying illumination in many different-sized nanopores. They next aim to explore in greater detail the mechanism underlying the increase in surface current when the green laser is applied to a nanopore, information that could lead to even more sensitivity and accuracy in DNA sequencing.
The research is funded by a $4.2 million grant from the National Institute of Health’s National Human Genome Research Institute under its “Revolutionary Sequencing Technology Development—$1,000 Genome” program, which seeks to reduce the cost of sequencing a human genome to $1,000.
Project Applies Software to Identify Flu Drug Candidates
By Mark Dwortzan
When 17-year-old Eric Chen was preparing his entry for the 2013 Google Science Fair, an online competition for teens with ideas to change the world, he set his sights on finding a systematic way to discover novel compounds for a new kind of anti-flu medicine effective against all influenza viruses, including pandemic strains. While pursuing his research at the National Biomedical Computation Resource at the University of California, San Diego, the high school junior came across just the right software for the job: a computational modeling tool, FTMap, developed by Professor Sandor Vajda (BME, Chemistry) and Research Assistant Professor Dima Kozakov (BME), that was designed to facilitate drug discovery. Applying FTMap to the problem, he was able to pinpoint several candidate compounds.
Impressed with the project and its potential, an international panel of scientists recently named Chen as winner of the 2013 Google Science Fair Grand Prize and of its 17-18 age category. Chen beat out 89 other semifinalists (whittled down to 15 finalists in July) from across the globe who submitted projects advancing solutions to everything from cancer detection to environmental protection. At the awards ceremony in Google’s headquarters in Mountain View, California in late September, he received $50,000 in scholarship funding, a 10-day trip to the Galapagos Islands, and other gifts.
Chen used FTMap to search for novel compounds that could shut down endonuclease, a critical viral protein that enables flu viruses to survive and thrive. Combining FTMap results with biological studies, he identified a number of novel, potent endonuclease inhibitors.
“Chen’s success demonstrates that the FTMap server provides insightful analysis of protein binding sites and thus facilitates drug discovery,” said Kozakov. “Introduced in 2011, FTMap already has more than 1,000 regular users worldwide, and it is easy enough to use that even a talented high school student can generate spectacular results.”
In a nutshell, FTMap searches the surfaces of proteins such as endonuclease for areas that can bind to candidate drug molecules.
“The program places small organic molecules as molecular probes to find binding ‘hot spots’ that are important for protein-drug interactions, and to select specific functional groups [of atoms within the molecular probes] that tend to bind with the highest affinity at these locations,” Vajda explained. “The information provided by FTMap can be used both for virtually screening large libraries of available compounds and for the design of new molecules that incorporate the functional groups identified by the mapping.”
Top-Tier Faculty to Advance High-Impact Field
By Mark Dwortzan
Synthetic biology brings together engineers, biologists and other life science researchers to conceive, design and build molecular biological systems that rewire and reprogram organisms to perform specified tasks. The field promises not only to yield new insights into biology but also to spark new technologies that could revolutionize healthcare, energy and the environment, food production, materials and global security. Recognizing the wide-ranging potential of synthetic biology and the trailblazing efforts of many of its faculty, the College of Engineering has launched the BU Center of Synthetic Biology (CoSBi) to advance this emerging discipline.
Poised to take a nationally preeminent role in advancing synthetic biology research, CoSBi unites core engineering faculty members that bridge diverse research interests, including microbial and metabolic engineering, immuno-engineering, cell reprogramming, computer-aided design and automation, single-cell analyses and systems modeling. In addition, the center involves leading researchers across the university with expertise in systems biology, leveraging their ability to reverse-engineer natural biological networks to help in the modeling, design and forward-engineering of synthetic biological networks with novel functions.
“We envision that CoSBI will serve as a focal point for activities in synthetic biology at Boston University and the larger Boston area, and help to advance the field toward applications in biomedical research, healthcare and other areas,” said Professor James J. Collins (BME, MSE, SE), one of the pioneers of synthetic biology, who directs the center.
CoSBi is located at 36 Cummington Mall, taking advantage of the newly renovated wet and dry facilities on the second floor and computational space on the third floor. Core faculty include Collins; Assistant Professor Ahmad “Mo” Khalil (BME), the center’s associate director; Assistant Professor Douglas Densmore (ECE, BME, Bioinformatics); and Assistant Professor Wilson Wong (BME), with 11 associate faculty members drawn from the College of Engineering, College of Arts & Sciences, and School of Medicine.
To advance its research agenda, CoSBi is expected to attract substantial government funding, major industrial collaborators and top-notch graduate students and postdoctoral fellows. The center will develop and support large-scale, collaborative projects, organize an annual symposium on synthetic biology featuring prominent researchers from around the world, and host a regular seminar series showcasing research leaders in the field.
To enable students of all levels to learn about the fundamentals and practice of synthetic biology and explore their interests in the intersection of engineering and molecular biology, the center will play an active role in supporting research training, education and outreach activities. Center administrators aim to appoint new research faculty and staff; develop new fellowships for and facilitate mentoring of graduate students and postdoctoral associates; design new courses and produce educational videos; run international synthetic biology competition teams and summer workshops; and build community for undergraduate, graduate and postdoctoral students studying synthetic biology.
“Synthetic biology is reshaping the discipline of biology, and attracting students and researchers with a diverse set of backgrounds,” said Khalil. “A central goal of CoSBi will be to prepare the next generation of synthetic biologists for this multidisciplinary type of research at an early stage, and to challenge them to think conceptually and creatively about how engineering can help in understanding life.”