Category: BME News
By Mark Dwortzan
Assistant Professor Ahmad (Mo) Khalil (BME, Bioinformatics) was selected as one of 77 innovative early-career educators to participate in the National Academy of Engineering’s (NAE) sixth Frontiers of Engineering Education (FOEE) symposium on October 26-29 in Irvine, California. Chosen from a highly competitive pool of applicants who are actively teaching in US engineering programs and have recently implemented significant innovations in their classes, the attendees were nominated by NAE members or deans.
A leading researcher in the field of synthetic biology, Khalil has also made his mark as an educator. In his first year on the Boston University faculty (2012-13), he received the College of Engineering Award for Excellence in Teaching in the BME Department. Based on a student vote, the award recognized his innovative teaching of the course Thermodynamics & Statistical Mechanics, in which he illustrated thermodynamics concepts with modern applications and examples in biomedical engineering. With funding from his 2013 National Science Foundation CAREER Award, he is now piloting a “synthetic biology bootcamp” for high school students—the first of its kind—that combines interactive lesson plans, hand-on lab experiences and an independent project.
At the conference, Khalil will join young faculty members who are advancing innovative approaches in a variety of engineering disciplines. In workshops, discussions and networking events, participants will exchange ideas and learn about best practices that they can apply at their home institutions.
“Participating in FOEE will help me improve as an educator both personally and in my efforts to more broadly effect positive change in engineering education,” said Khalil. “I am also enthusiastic to contribute to and lead critical discussions centered on how we, the broader engineering community, envision shaping and standardizing synthetic biology curriculum across institutions of higher learning.”
The Frontiers of Engineering Education (FOEE) program draws top university faculty to explore how best to prepare the next generation of engineers to take on societal challenges, from updating course content to revamping how that content gets delivered. The ultimate goal of FOEE is to foster a vibrant community of emerging education leaders who can help boost the engineering and innovation capability of the nation.
Rapid, Point-of-Care Device Detects Virus in Complex Blood Samples
By Mark Dwortzan
By late January, 1.4 million people in Liberia and Sierra Leone could be infected with the Ebola virus. That’s the worst-case scenario of the Ebola epidemic in West Africa recently offered by scientists at the US Centers for Disease Control and Prevention. The CDC warns that those countries could now have 21,000 cases of the virus, which kills 70 percent of people infected.
One of the big problems hindering containment of Ebola is the cost and difficulty of diagnosing the disease when a patient is first seen. Conventional fluorescent label-based virus detection methods require expensive lab equipment, significant sample preparation, transport and processing times, and extensive training to use. One potential solution may come from researchers at the College of Engineering and the School of Medicine, who have spent the past five years advancing a rapid, label-free, chip-scale photonic device that can provide affordable, simple, and accurate on-site detection. The device could be used to diagnose Ebola and other hemorrhagic fever diseases in resource-limited countries.
The first demonstration of the concept, described in the American Chemical Society journal Nano Lettersin 2010 and developed by Professor Selim Ünlü’s (ECE, BME, MSE) research group in collaboration with Professor Bennett Goldberg (Physics, BME, ECE), showed the ability to pinpoint and size single H1N1 virus particles. Now, after four years of refining the instrumentation in collaboration with Associate Professor John Connor (MED) and other hemorrhagic fever disease researchers at the University of Texas Medical Branch, the team has demonstrated the simultaneous detection of multiple viruses in blood serum samples—including viruses genetically modified to mimic the behavior of Ebola and the Marburg virus.
Mentioned in Forbes magazine as a potentially game-changing technology for the containment of Ebola, the device identifies individual viruses based onsize variations due to distinct genome lengths and other factors. Funded by the National Institutes of Health, the research is showcased in ACS Nano.
“Others have developed different label-free systems, but none have been nearly as successful in detecting nanoscale viral particles in complex media,” said Ünlü, referring to typical biological samples in which a mix of viruses, bacteria and proteins may be present. “Leveraging expertise in optical biosensors and hemorrhagic fever diseases, our collaborative research effort has produced a highly sensitive device with the potential to perform rapid diagnostics in clinical settings.”
Whereas conventional methods can require up to an hour for sample preparation and two hours or more for processing, the current Boston University prototype requires little to no sample preparation time and delivers answers in about an hour.
“By minimizing sample preparation and handling, our system can reduce potential exposure to healthcare workers,” said Connor. “And by looking for multiple viruses at the same time, patients can be diagnosed much more effectively.”
The shoebox-sized prototype diagnostic device, known as the Single Particle Interferometric Reflectance Imaging Sensor (SP-IRIS), detects pathogens by shining light from multi-color LED sources on viral nanoparticles bound to the sensor surface by a coating of virus-specific antibodies. Interference of light reflected from the surface is modified by the presence of the particles, producing a distinct signal that reveals the size and shape of each particle. The sensor surface is very large and can capture the telltale responses of up to a million nanoparticles.
In collaboration with BD Technologies and NexGen Arrays, a BU Photonics Center-based startup run by longtime SP-IRIS developers David Freedman (EE10) and postdoctoral fellow George Daaboul (BME’13), the research team is now working on making IRIS more robust, field-ready and fast—ideally delivering answers within 30 minutes—through further technology development and preclinical trials.
SP-IRIS devices are now being tested in multiple labs, including a Biosafety Level-4 (BSL-4) lab at the University of Texas Medical Branch that’s equipped to work with hemorrhagic viruses. Other tests will be conducted at BU’s National Emerging Infectious Diseases Laboratories (NEIDL) once the facility is approved for BSL-4 research. Based on the team’s current rate of progress, a field-ready instrument could be ready to enter the medical marketplace in five years.
Find out more about SP-IRIS in this National Academy of Engineering radio clip.
Joint Research Focused on Medical Imaging and Image-Guided Interventions
By Mark Dwortzan
Boston University College of Engineering Assistant Professor Darren Roblyer (BME) and Brigham & Women’s Hospital radiologist Srinivisan Mukundan are exploring a strategy that combines a new optical imaging device developed by Roblyer with emerging magnetic resonance imaging (MRI) techniques to probe malignant brain tumors during chemotherapy treatment. Their research could enable clinicians to monitor the effectiveness of chemotherapy over the course of treatment and implement changes to chemotherapy drugs and dose levels as needed.
The project is one of five now receiving funding through an ongoing partnership between Boston University and Brigham & Women’s Hospital. On September 12 at the BU Photonics Center, Dean Kenneth R. Lutchen and Dr. Steven Seltzer, Chair of the BWH Department of Radiology, announced the second year of the partnership, which has already provided one year of seed funding to projects ranging from image-guided cancer drug delivery to early detection of heart disease.
“The goal is to leverage synergies between Brigham & Women’s Hospital’s Radiology Department in imaging and image-guided interventions with the College of Engineering’s strengths in developing new materials and technologies as well as novel techniques for processing images and large data sets,” said Associate Professor Tyrone Porter (ME, BME, MSE), who is coordinating the partnership. “The hope is to stimulate research collaborations between the two campuses and develop a National Institutes of Health training program in clinical imaging and image-guided interventions.”
The brainchild of Lutchen and Seltzer, the BU-BWH partnership brings together world-class expertise and equipment from Boston University entities such as the BU Photonics Center and the BU Center for Nanoscience & Nanobiotechnology, and from the BWH Department of Radiology, home to the National Institutes of Health’s National Center for Image-Guided Therapy and the Advanced Multimodality Image Guided Operating Suite (AMIGO). Joint research between the two campuses could result in less invasive, more accurate medical imaging and image-guided interventions.
“There’s no question that in so many dimensions, imaging is at the foundation of a tremendous amount of potential breakthroughs in medical discoveries and practice, but there are huge challenges from a scientific and technical point of view,” said Lutchen. “We’ve got tons of interested students and faculty here that need and want to use imaging technologies to address interesting and important questions.”
First-round projects include the engineering of a new “molecular imaging” MRI contrast agent for detecting early calcification of the aortic valve; the combination of ultrasound and MR data to evaluate the elastic properties of tissues, which are associated with pathological indicators of disease; a clinical decision support system for patient-specific cancer diagnosis and management; and ultrasound-guided delivery of chemotherapy drug-laden nanoparticles to metastasized lung cancer cells in the brain. Applications for second-round projects are now underway.
All projects involve at least one principal investigator from each of the partnering institutions, who jointly advise a doctoral student on a project that could positively impact clinical practice. Participating ENG faculty include Professors Joyce Wong (BME, MSE), Paul Barbone (ME, MSE), Venkatesh Saligrama (ECE, SE) and Yannis Paschalidis (ECE, SE); Associate Professor Porter; and Assistant Professor Roblyer.
“The fields of biomedical imaging and bioengineering have been converging and collaborating for decades, and that collaboration continues to get closer and closer,” said Seltzer, noting a burgeoning clinical need for advanced technologies in functional and molecular imaging; information technologies ranging from data mining to image processing; and minimally-invasive diagnostic and therapeutic procedures guided by high-technology imaging techniques.
Project Enhances Mobility for the Visually Impaired
By Mark Dwortzan
One of this year’s BME senior design teams took second place in the National Institute of Biomedical Imaging and Bioengineering (NIBIB) Design by Undergraduate Biomedical Engineering Teams (DEBUT) competition. The team, which created a high-tech glove to enhance the capabilities of the traditional white cane used by people with visual impairments, will receive $15,000 at a ceremony at the Biomedical Engineering Society (BMES) conference in October.
The BME team’s entry, a “Sensory Substitution Glove for the Visually Impaired,” is designed to enable users to detect obstacles at head-height as well as sudden drop-offs, and do so early enough to change course and prevent injury. Equipped with ultrasound and infrared sensors, an accelerometer, a microprocessor and a small speaker, the backside of the glove scans the user’s surroundings and produces vibrational signals that cue him or her to avoid impediments within a one-to-two-meter range.
“It is truly an honor to be recognized along with my team members and advisor for this prestigious award,” said Poling Yeung, who developed the Sensory Substitution Glove with fellow BME 2014 graduates Michaelina Dupnik and William Moik under the guidance of Assistant Professor Jason Ritt (BME). “We hope that with funds from our award, the next group in the Ritt Lab can further advance our prototype and possibly begin clinical trials.”
“There have been many attempts at making sensory substitution mobility aids, including a few currently on the market, but so far they’ve seen limited adoption by the visually impaired population,” said Ritt. “The importance of this team’s work was to try to improve usability by adding intuitive motion control that expands what the glove senses.”
Ritt had challenged the team to create an inexpensive glove that would detect the potential for a fall based on a drop in ground level (e.g., due to steps, ditches and holes). A previous version developed by earlier senior design teams in his lab focused on object detection, but input from the Perkins School for the Blind necessitated a redesign that could accommodate sudden drop-offs. Yeung, Dupnik and Moik solved the problem by identifying and implementing suitable range-finding (ultrasound and infrared) sensors, and programming a microprocessor to convert outputs from these sensors into tactile vibration frequencies at the user’s index finger. By making certain gestures, the user can expand or restrict the glove’s sensing domain.
The first place team, from Johns Hopkins University, will receive $20,000 for its entry AccuSpine, a probe that uses lights and vibration to more safely and effectively place screws during spinal fusion surgeries. Sharing third place honors and each receiving $10,000 are a team from Rice University that designed a device designed to improve nutrient delivery to newborns, and a team from University of California, Riverside that designed a diaper-based lateral flow device for early detection of dehydration and bacterial infection.
“We are very proud to announce the winning projects,” said NIBIB Director Roderic I. Pettigrew. “All four of them show how a fresh perspective can create inexpensive, effective and transformative technologies to solve longstanding challenges in healthcare. I am excited to see how this next generation of biomedical engineers will continue to create technology that is better, faster and less costly.”
Sixty-three eligible entries were received from 33 universities in 19 different states. Judging was based on the significance of the problem being addressed, the innovation of the design, the existence of a working prototype, and the project’s potential impact on clinical care. The organization administering the competition, the NIBIB, is part of the National Institutes of Health.
How ENG is Transforming the Classroom through Digital Learning Technology
By Mark Dwortzan
You’ve seen it before: a single faculty member on stage delivering a lecture to row after row of students dutifully taking notes, with little or no interaction between the lecturer and the note takers. It’s been the model for science and engineering education for more than a century, but a new paradigm is emerging that turns this model on its head, all while improving student outcomes: the flipped classroom.
In the flipped classroom, students view lectures online while at home, and spend classroom time applying what they learned both individually and in small group exercises. Collaborating with their peers at round tables in a revamped “learning studio” and guided by the faculty member and a team of teaching assistants moving from table to table, they solve problems that reflect the scope of the lecture material. And the difficulty: some problems are chosen based on trouble spots identified via mandatory quizzes that accompany the online lectures to assess student comprehension.
This is where engineering education is heading, and Boston University, which launched its Digital Learning Initiative (DLI) last year to spearhead innovative projects in online learning at all of its schools and colleges, is fully on board. The DLI recently awarded $80,000 to fund a College of Engineering proposal to enhance two core undergraduate engineering courses, EK127 (Introduction to Engineering Computation) and EK307 (Electric Circuits), with a suite of classroom-flipping, studio-based educational technologies and techniques. Lessons learned from this pilot program could be used to upgrade the learning experience in other engineering courses.
Professor Thomas Little (ECE, SE), the College of Engineering’s associate dean for Educational Initiatives, sees these pilot projects as part of a broader College-wide effort to use digital learning technologies—from tablets to Massively Open Online Courses (MOOCs)—to bring engineering education into the 21st century.
“Inspired by the success of these technologies in other disciplines and energized by the support and training that the DLI is providing, we are developing new ways to improve what’s important to the student: learning; retention; and career preparation,” said Little.
In both EK127 and EK307, instructors and teaching assistants funded by the DLI grant will develop course content using edX, a non-profit online platform that offers interactive online classes and MOOCs—not as a vehicle to reach large numbers of students via the Internet, but as a tool to boost active learning in the classroom. For each class meeting, they will record a video on the material students need to learn for that class, make it accessible through the edX platform, use edX assessment tools to set up online quizzes, and design active learning exercises.
The instructor for EK127, 2014 Metcalf Cup and Prize winner and Assistant Professor Stormy Attaway(ME), has been gradually flipping the course over the last three years. With the new funding—and support by “course builders” such as Declan Bowman (BME’15), one of the first students in the College’s STEM Educator-Engineer Program (STEEP)—she aims to completely flip the course. Once all course content is placed online along with assessments, Attaway will devote all classroom time to active learning in Photonics Room 117, an instructional space that the College is converting into an active learning studio complete with round tables and modern electronic displays.
“At this point there is ample evidence that flipped classes with active learning environments work; the focus is now on how to get faculty to adopt these best practices,” she said, noting that transforming a traditional lecture into an online course module—breaking it into bite-sized chunks, recording the video and hosting it on the edX platform—can take up to 20 hours. “Although my primary goal is to improve the learning experience for my students, my secondary goal is to be a resource for my colleagues so that I can help them transform their courses.”
With his portion of the DLI funding, Professor Mark Horenstein (ECE) is developing a series of 30-minute course modules to aid fellow EK307 instructors who wish to flip their classrooms or enhance them with online instruction. Always available to students and consisting of animated, voice-over PowerPoint and/or videotaped lectures, the modules are intended to provide an interactive learning tool to supplement traditional textbooks, lectures, discussions and lab work.
“In my experience, students learn in a myriad of different ways,” said Horenstein. “Some students thrive in the traditional lecture/homework environment, while others learn best in a hands-on setting, for example, when a small group works with a professor during office hours on specific problems and concepts. Still other students learn best in the laboratory, where they can transfer lecture/discussion concepts into the hands-on design of electric circuits that solve a problem or meet a desired specification. The hope is that these modules will service all of these learning styles, and more.”
The two pilot projects leverage earlier digital technology-enabled active learning efforts by Lecturer Caleb Farny (ME) in EK301 (Engineering Mechanics) and Assistant Professor Martin Steffin (BME, MED) in BE 209 (Principles of Molecular Cell Biology and Biotechnology), and pioneering work by faculty in the Physics Department in peer-based learning and the use of studio space.
“As these early adopters show what’s possible, we look forward to bringing additional faculty on board,” said Little. “By working with people who are taking risks to do the right thing for students, we’re going to demonstrate the potential of digital learning technologies to make a difference for our engineering students.”
By Mark Dwortzan
Thanks to a generous gift by Professor and Dean Emeritus Charles DeLisi (BME, Bioinformatics), the College has established the Charles DeLisi Award Lecture and Ceremony. Set to launch in 2015, this annual event will feature a lecture by a College of Engineering faculty member or alumnus who has made outstanding contributions to engineering and society.
Charles DeLisi Distinguished Lecturers may include researchers who have contributed significantly to the advancement of their field, executives who have helped shape their industry, and/or entrepreneurs who have invented or mentored transformative technologies that have enhanced our quality of life. The lectures will be open to the entire Boston University community and the general public.
“There are a lot of unusually talented people among our faculty and alumni who have made contributions that make us all very proud to be part of the BU College of Engineering community,” said DeLisi. “This program will provide us with the opportunity to express our gratitude for their contributions, while enabling them to share their work with a wide audience of scientists, engineers and the public in one of the world’s most important high tech communities.”
Widely considered the father of the Human Genome Project, DeLisi was an early pioneer in computational molecular biology, and also made seminal contributions to theoretical and mathematical immunology. He currently serves as Metcalf Professor of Science and Engineering, and continues to direct the Bimolecular Systems Laboratory, where more than 100 undergraduate, graduate and post-doctoral students have trained.
As Dean of the College of Engineering from 1990 to 2000, he recruited leading researchers in biomedical, manufacturing, aerospace, mechanical, photonics and other engineering fields, establishing a research infrastructure that ultimately propelled the College to its ranking in US News & World Report’s top 40 engineering graduate schools. In 1999 he founded—and then chaired for more than a decade—BU’s Bioinformatics Program, the first such program in the nation.
Funding to Enable Scale-Up of Counterfeit Drug Detector
By Mark Dwortzan
One of the biggest challenges in global health is the proliferation of drugs that do not perform as labeled, due to false claims about their effectiveness or faulty manufacturing and storage practices. Up to 50 percent of medicines distributed in developing countries are either counterfeit or significantly substandard, and procedures used to check their quality are largely inaccurate, not to mention slow, expensive and complicated. The result: hundreds of thousands of preventable deaths each year.
To address the problem, a team of Boston University biomedical engineers and public health researchers led by Associate Professor and Howard Hughes Medical Institute ProfessorMuhammad Zaman (BME, MSE) has spent the past four years developing and field-testingPharmaChk, a user-friendly, low-cost, portable, fast and accurate detector for screening counterfeit and substandard medicines. Once deployed on a large scale, the technology could substantially improve fragile health systems and save countless lives—including those of mothers and newborns suffering from malaria, sepsis and other diseases—in many developing nations.
Recognizing the potential of PharmaChk to vastly improve health outcomes for this population, theSaving Lives at Birth: A Grand Challenge for Development program has awarded Zaman’s team with a $2 million “transition-to-scale” grant to demonstrate the impact of its technology at scale—one of only four such awards among 30 announced at the Saving Lives at Birth’s annual DevelopmentXChange conference in Washington, DC.
The PharmaChk team was among 52 finalists at the conference (winnowed down from an original field of 550 teams from dozens of countries) competing for funding to realize and scale disruptive technologies and other innovative ideas to save the lives of mothers and newborns in the poorest places on the planet. Zaman’s team was the only engineering group to receive a “transition-to-scale” grant and one of a select few to do so within two years of receiving a $250,000 seed grant from the program,
“This is a huge honor not only for our team but also for Boston University, and underscores the university’s leadership and strong commitment to technological innovation and global health,” said Zaman. “We are deeply honored to be the first team at BU to be awarded the transition-to-scale grant and are eager to work with our partners in Boston and around the world to address this huge global challenge.”
Named one of “Ten World Changing Ideas” in its 2013 year-end roundup article on proven, scalable innovations that could dramatically impact society in the near future, PharmaChk was developed by Zaman and graduate students Darash Desai (BME), Nga Ho (BME), Andrea Fernandes (SMG, SPH) and research scientist Atena Irani Shemirani (BME). The user places a pill into a small testing box which instantly reports the amount of active ingredient found in the pill. The device is simple to operate and verifies a drug’s safety in a matter of minutes, thanks to complex, microfluidic, lab-on-a-chip technology developed in the Zaman lab.
Building on earlier work testing a prototype in Ghana, the team plans to use the new funding to incorporate feedback from local users of PharmaChk and scale the technology with the help of partners in Ghana and the US Pharmacopeial (USP) Convention in Rockville, Maryland. By ensuring that essential medicines are safe at all points along the supply chain—from manufacturers to distributors to suppliers in rural areas—Zaman’s team aims to have a profound impact on the health of mothers and newborns.
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 USP Convention under the Promoting the Quality of Medicines (PQM) program funded by USAID. USP has provided both financial and logistical support in Ghana through its Center for Pharmaceutical Quality Research Center. PharmaChk has received additional funding from the Wallace H. Coulter Foundation, and support and mentorship from the Center for Integration of Medicine and Innovative Technology (CIMIT) (including critical assistance from CIMIT Accelerator Program Executive Wolfgang Krull), and the National Collegiate Inventors and Innovators Alliance.
Launched in 2011 to stimulate innovative preventative and treatment methods to improve health outcomes for mothers and newborns around the time of delivery, the Saving Lives at Birth partnership includes the US Agency for International Development (USAID), the Government of Norway, the Bill & Melinda Gates Foundation, Grand Challenges Canada (funded by the Government of Canada) and the UK’s Department for International Development (DFID). Supported by a $50 million commitment, Saving Lives at Birth has funded 59 innovations in its first three rounds, aiming to address the 289,000 maternal deaths, 2.9 million neo-natal deaths, and 2.6 million stillbirths that occur each year.
By Sara Cardelle, USAID
Imagine rummaging through your medicine cabinet for a vital prescription. Once found, you pop the lid and tap out a few pills into your palm. If you live in a country that strictly regulates pharmaceutical production and distribution, you assume the pills are safe and take them without a second thought.
But what if these protections were not provided? What if you were stricken by an illness that required medication that you couldn’t be sure was safe or effective? What if you learned too late that this medication contained no active ingredient, was degraded, or mixed with toxic components?
For millions of people in developing countries, these questions are all too real.
In 1995, a meningitis epidemic hit Niger, in West Africa. Although the Government of Niger carried out an efficient vaccine program, more than 50,000 people were administered fake vaccines that contained no active ingredient, resulting in 2,500 deaths. The vaccines, donated by a country that thought they were safe, had been bottled and labeled to look like true vaccines.
Similar incidents continue to occur worldwide. Counterfeit drugs, which are estimated to be as high as 30 percent of all drug sales in the developing world, can cause severe side effects or death or, because they often don’t contain the correct amount of active ingredients, can allow for disease progression and cause drug resistance. Globally, more than 100,000 people die every year as a result of these dangerous drugs and this likely represents a significant underestimation. High profit margins and minimal risk, along with lack of political commitment and weak medicines regulation and enforcement drive the counterfeit market.
A parallel problem exists with substandard medicines, whether imported or produced locally. In these cases, drugs are not produced in accordance with accepted good manufacturing practices or shipped or stored properly, rendering them ineffective at best. In 2012, a contaminated cardiovascular medicine was linked in Pakistan to the death of more than 200 patients in just a few days and was responsible for sickening 1,000 after lethal amounts of an antimalarial drug were accidentally mixed with the medicine during manufacturing.
This is the dire and sometimes fatal scenario that a promising and innovative new device called PharmaChk is hoping to prevent. PharmaChk, a fast, easy and inexpensive screening technology for counterfeit and substandard medications, is being developed at Boston University to help combat the perils of poor quality drugs in the developing world.
Several programs at USAID, including Saving Lives at Birth: A Grand Challenge for Development, have backed this effort.
“Our goal is to comprehensively address the limitations of current technologies and provide detailed information on drug quality at all points in the supply chain,” says Muhammad Zaman, an associate professor at Boston University and the lead researcher developing the device.
Zaman, who teaches biomedical engineering, has both a professional and personal interest in combatting counterfeit drugs in the developing world. He grew up in Pakistan and remembers that his “mother would take us all across the town so we could get our medicines and vaccines at a reputable place.” Those long treks would eventually inspire him to tackle the counterfeit and substandard medicine crisis.
Read more, here.
Asst. Prof. Xue Han talks about her work in the new field of optogenetics
By Barbara Moran, BU Today
Xue Han investigates Parkinson’s disease with an unusual tool: light. Han is a pioneer in the young field of optogenetics, in which scientists reengineer nerve cells, or neurons, to respond to light, using molecules called opsins. Like ice cream, opsins come in many flavors—there’s rhodopsin in the human eye and halorhodopsin in bacteria, for instance—but they all share one key characteristic: they change shape when exposed to light.
By finding ways to implant opsins into neurons, Han, a College of Engineering assistant professor of biomedical engineering, has given researchers a simple tool to turn neurons on and off, and thereby study their function. The technique is now widely used to study brain activity, and it is leading to a better understanding of diseases and treatments.
In April 2014, Han traveled to Washington, D.C., where President Obama awarded her a Presidential Early Career Award for Scientists and Engineers, the US government’s highest honor for science and engineering professionals in the early stages of their independent research careers.
BU Today spoke recently with Han.
BU Today: Who came up with the idea of using light to turn neurons on and off?
Han: Using light to control cells is not so new. In our retina there are all these rhodopsins that naturally are sensitive to light, but we can’t easily engineer the whole system into neurons. So the really novel part was sensitizing neurons to light so they’re easy to use.
So how did I get involved in this whole thing? I started my postdoc at Stanford in 2005, and that’s the same time that Ed Boyden, now an MIT associate professor, along with Karl Deisseroth, used this molecule called channelrhodopsin. They put it in neurons, and they were able to drive neural activities with the light. And the beauty of channelrhodopsin is that it’s a very small protein and it’s very easy to use.
Then Ed and I were thinking, since there’s a technology to excite neurons, can we also silence them? That led to the discovery of halorhodopsin, which allowed us just to do that. But it doesn’t do it really well. Who knows why? These are from bacteria, and you’re putting them in mammalian cells. That’s the complexity of biology.
So we said, let’s find a better one. We screened a whole bunch of proteins similar to halorhodopsins, and we found some other things that were similar, like proton pumps. We did not think they would work, but we thought, you know what? Let’s throw a couple in and see what happens. And we did that, and found that these proton pumps are way more effective in silencing neurons. And more importantly, from what we have tested, it’s safe for the neurons. It’s a powerful engineering tool—that we can excite or silence neurons now.
Are the tools getting closer to being used in patients?
Right now, my group is interested in how, in a disease like Parkinson’s, deep brain stimulation works. There are all these hypotheses about deep brain stimulation and its therapeutic effects. So the idea is that if you use light, then we can understand the mechanism and simultaneously see how the neurons respond and how they are contributing to Parkinson’s disease. These neurons in the Parkinsonian brain tend to oscillate or synchronize at a frequency of 20 hertz or so.
All the neurons in the brain, or just the Parkinsonian ones?
The Parkinsonian ones in a particular part of the brain.
All the neurons affected with Parkinson’s in a certain part of the brain are talking to each other at 20 hertz?
Not all of them. But somehow, more are talking to each other than normal.
But that’s what people find. If you think about Parkinson’s in particular, it’s a dopamine neuron loss. We are trying to figure out how this dopamine loss leads to the generation of these pathological oscillations in the brain. And then what’s the relationship of these oscillations to the symptoms?
Do other neurological diseases have different pathological oscillations?
That’s a great question. Can we establish some sort of oscillations as biomarkers of specific mental disorders? I think this is definitely a very interesting area. There’s certain evidence that a frequency around 40 hertz is associated with schizophrenia, but a coherent understanding would really help.
Why does Parkinson’s interest you?
I think for Parkinson’s, we are at a stage that things are converging. There’s a very good animal model for Parkinson’s, and the symptoms can be easily quantified, more easily than major depression or other types of mental disorders, like schizophrenia.
You’re married to Ed Boyden, who is also a leader in optogenetics. Do you two collaborate?
Well, we collaborate still. It’s hard not to collaborate, right? But you know, we have two small kids, so as soon as we start a conversation someone spills milk, and that conversation goes nowhere.
Do you tell your kids about your work? Are they interested?
Certainly there are scientific terms we use that our babysitter would not really understand. This morning my son was asking me how the Earth was generated. I told him the Earth was here when he was born, and I told him I was here, and so I started to explain it to him a little bit. It’s hard not to.
Where do you think diagnosing and treating neurological diseases will be 20 or 30 years from now? How will your work fit it?
A lot of parts can be replaced, but when it comes to the brain, we are not there yet. In Parkinson’s and Alzheimer’s, we know the neurons are dying. Is there some replacement we can do? If we have a biomarker, we can probably start to develop more human therapies. So that’s what I’m hoping: we’ll treat these disorders before we’re old enough to get them ourselves. So we need to hurry up.
See video (courtesy of WBUR).
Klapperich inventing technology that could change future of primary care
By Barbara Moran, BU Today
Catherine Klapperich moves fast, talks fast, and has at least 15 different ideas rolling through her head at the same time. How, for instance, can she keep her postdocs on track, guide 134 undergrads through their senior project, and meanwhile invent new technology that may change medicine as we know it? She arrived a few minutes late for an interview, preoccupied with a more immediate concern: she had accidentally spilled water on her iPhone. She ran down to her lab to stick it into the vacuum oven, hoping that would dry it out. Then she ran back to her office and sat down to talk.
Klapperich holds three associate professorships at BU, in the College of Engineering biomedical engineering and mechanical engineering departments and in the Division of Materials Science and Engineering. She also directs the Center for Future Technologies in Cancer Care. Her lab creates point-of-care diagnostics—tools, like a pregnancy test stick, that doctors and consumers can use to immediately test such conditions as high cholesterol or diagnose illnesses like strep throat. One critical need in the developing world is a rapid test for HIV viral load—the amount of HIV in a patient’s blood. The number helps doctors monitor the disease, decide when to start treatment, and determine if HIV medications are working.
BU Today recently spoke to Klapperich about her work.
BU Today: A lot of your work focuses on public health issues. Where does that interest come from?
Klapperich: When I got my PhD at Berkeley, I was studying artificial hips and knees. They have a metal part and a plastic part, and we were engineering the plastic part. I became interested in how cells interact with biomaterial surfaces. And that led into my postdoc, which focused on how cells interact with biomaterials at the level of gene expression.
At that time, gene chips were just becoming a routine tool in the laboratory. And I was completely floored by all the steps to use them: breaking the cells open, getting the DNA or RNA out, amplifying it, putting it on a chip, and then turning on the reader to figure out the expression levels. It was a huge number of steps. As an engineer I thought, why? So I became really interested in doing this stuff in a turn-crank way, where I wouldn’t have to do all the little steps.
A machine would do it instead?
The machine would do it. The gene chip is a wondrous thing. And yet it took two and a half days to make the material to go onto that chip. So I became very focused on the sample preparation process. Then it became clear to me that this is why point-of-care diagnostics do not exist in the numbers that they should. Because yeah, we have this chip and it can tell us all this information, but all this prep requires someone with a lot of laboratory skill.
So you want to take the diagnostic chip, have some patient spit on it, and then have the answer show up without two and a half days of sample prep?
Right. And so for DNA and RNA it’s hard, because most of it is inside of our cells or inside the bugs that infect us. So you have to break cells apart and amplify the DNA or RNA—make many, many copies. Then you tag them with something like a fluorescent protein that allows you to see them. So we need to do three things: we need to extract, we need to amplify, we need to read. Let’s do those three things as simply as we can, in as few steps as we can, as reliably as we can. We want to be the test kitchen for this work.
This field has grown a lot, even in the last 10 years.
Yeah—now you can walk into Walgreens and there’s a little blue sign hanging over the aisle, where it says things like Foot Powder and Toothpaste, and it says Diagnostics. And I remember the first time I saw that a few years ago. I thought, what? That’s crazy! This is now a thing in the aisle.
It’s a noun.
Exactly. There are the glucose strips, there’s a cholesterol test. You can buy a drug test—
A drug test for what?
For your kid. This is the marijuana one.
Really? This box you’re showing me is a marijuana test kit?
Yeah. This is great. You can buy the 4-drug test, the 7-drug test, or the 12-drug test. You can test your kid for depressants, barbiturates, methadone, benzodiazepines, opiates, ecstasy, amphetamines, methamphetamines, cocaine, marijuana, and Oxy. It’s pretty amazing. And it’s just pee. I think it really empowers people to have information about their own health. If you think about cholesterol tests, and HIV yes/no, respiratory infections, strep, these things can be done by the patient. That can save an office visit, which saves money; it saves the potential of infecting other people; it saves the time of the clinician. I think it will change the primary care model a lot.
What’s the first thing out of your lab that might make it into Walgreens?
It’s an HIV viral load test that we’re working on with a company in San Francisco. A colleague told me last week, from his clinic in South Africa, “We need a viral load test. If people come to see me and I tell them, ‘I’m going to take your blood, come back to get the results,’ 50 percent of them just don’t come back. Something that would help tomorrow is if I could give that person their results right there. And if their viral load is suppressed, then I don’t have to expend any resources seeing that person until the following year.”
They’re testing that right now in South Africa. That could be deployed in a primary care clinician’s office, and that’s the first thing that will come from our laboratory.
That will be cool.
Yeah, it will be very cool.