The Bright Idea That Sparked More Bright Ideas
Engineers solve grand challenges by forming interdisciplinary centers
By Liz Sheeley
Academic disciplines in modern universities were decided in the late 19th century, when they created this complete orthogonal set of human knowledge,” says Professor David Bishop (ECE, Physics, MSE, ME, BME). “But the societally important problems are far more sophisticated and far more complex than one single discipline can solve.”
As director of the $20 million CELL-MET Engineering Research Center (ERC) funded by the National Science Foundation (NSF), Bishop heads up a team of interdisciplinary researchers who are working to synthesize personalized heart tissue for clinical use.
The ERC is one of nine interdisciplinary centers within Boston University’s College of Engineering. The Biological Design Center (BDC) and the Neurophotonics Center are two other such major hubs for collaboration between researchers not just within the College of Engineering, but also throughout BU and other universities.
Although each center’s goals focus on solving a major research problem—whether those are specific goals like building personalized heart tissue and developing technologies to understand the brain, or a broader goal of working to understand life’s design principles in order to be able to re-engineer them—all of the centers rely on collaboration and cooperation between disciplines.
“Heart disease, energy, cancer, diabetes, climate change—these are all problems that are major societal challenges,” says Bishop. “But a group of physicists, a group of chemists or a group of electrical engineers aren’t going to solve any of those massive challenges by themselves.”
These three centers together boast almost 50 faculty members working with a common drive to learn how biological processes work and to develop technologies, processes and techniques to under- stand those processes on a deeper level.
“Part of understanding how something works is to try to build it, and when the expected outcome isn’t the actual outcome, it’s clear we have a disconnect somewhere,” says Professor Chris Chen (BME, MSE), the BDC’s director. “We cycle through a feedback loop of designing what we think will generate the desired protein, cell or tissue, building it, testing what we’ve made and then learning what needs to be adjusted for the next iteration.”
“I’m inspired by the number and diversity of collaborations across labs that have already developed in the short time since we founded the BDC,” says Jessica Tytell, executive director of the BDC. “These teams are building new ideas, approaches and solutions to a broad array of challenging issues.”
Chen says that the goal of the BDC is to understand how biological systems work so that they can then reengineer them for a variety of applications. He is also the deputy director of the ERC, working with Bishop on building personalized heart tissue. By training, Chen is a tissue engineer who studies the role of forces and architecture in controlling how cells organize and function, with a focus on cardiac and vascular tissues. The goal of his own group within the BDC is to understand how to generate cardiac muscle and blood vessels, what happens to them during injury and why those processes happen the way they do on a molecular level.
“All of the members of the BDC share a common purpose to understand the underlying design of biology so we can replicate it,” says Chen. “There are many scientists out there who don’t operate like that.”
Assistant Professor Ahmad ‘Mo’ Khalil (BME) and Assistant Professor Wilson Wong (BME) are two engineers who do. “The synthetic biologists like Mo Khalil and Wilson Wong are trying to build new genetic circuits, signaling pathways, transcription factors and receptors, so in a sense they are making all of the parts that are used to control cells,” says Chen. “And I’m trying to control cells and turn them into tissue—so we realized we were part of the same field even though our technical disciplines aren’t the same.”
Just as Chen can benefit from the synthetic biologists’ toolkit, they can benefit from another discipline that relies on circuits and signals. BDC member Associate Professor Douglas Densmore (ECE, BME) is an electrical and computer engineer who builds tools for synthetic biologists like Khalil and Wong. Densmore leads a team working on a $10 million NSF-funded effort to quantify synthetic biology, using a computer engineering approach to create a toolbox of carefully measured and cataloged biological parts that can be used to engineer organisms with predictable results.
Bishop says Chen’s work in tissue engineering was a spark for the beginning of the ERC. “Stem cells can become any kind of adult cell—and there’s hundreds of different kinds of cells in the human body—so what happens is that those stem cells, via clues that we’re only just beginning to understand, decide which type of adult cells to become,” says Bishop. “The interesting discovery, what really drove the ERC’s establishment, was by Chris Chen. His research has shown that it’s really a nano-mechanical environment that drives the stem cell maturation process.
“If you take a stem cell and you put it in an environment that feels like a heart-muscle environment, somewhere that’s contractile, the cell says, okay, then I’ll become a cardio myocyte,” says Bishop. “Or if you put it in a place that feels like skeletal muscle or a place that feels like skin, or bone, or kidneys or any other type of tissue environment, that is what causes a stem cell to grow and transform into the type of cell it’s supposed to be—that was a huge breakthrough.”
The ERC has four principal researchers within BU: Bishop, the ERC director and a nanotechnologist; Professor Alice White (ME, MSE, BME), who is also a nanotechnologist; Professor Thomas Bifano (ME, MSE, BME), who works on imaging; and Chen, the tissue engineer.
“We believe that to achieve the center’s goal, we will need to be innovative at the nexus of several academic disciplines,” says Bifano. “Our team has organized into a cohesive and cooperative group of scholars from diverse backgrounds and we have established learning communities in which complementary expertise and perspectives fuel our collective progress and we have all become both students and teachers.”
Bishop says his team along with White’s are beginning to build mechanical environments, systems and devices for Chen’s team to use. Bifano and his team are beginning to develop microscopes that image tissue in various ways for Chen’s team. “What we’re trying to do is take these things, and kind of bring them together, and create a kind of shared common understanding about the challenges and opportunities,” says Bishop.
“A wonderful aspect of the ERC is the opportunity for everyone to be part of something much larger than a single research group,” White says. “We’ve met students who were part of ERCs decades ago and they still describe it as a transformational experience—learning to communicate with experts in different disciplines, figuring out how to integrate into the larger team and, finally, having the opportunity to make a much larger impact than is usually possible as a student.”
These types of multidisciplinary collaborations are also what the director of the Neurophotonics Center, Professor David Boas (BME), is focusing on. The Neurophotonics Center’s mission is to cultivate new technologies for researchers to study the brain—and new technologies hopefully mean new discoveries. The center opened in the fall of 2017 and is the first facility of its kind in the United States and only the second in North America.
“We want to help spark collaboration between researchers who are building a new technology and researchers asking a specific scientific question,” says Boas. And his own work showcases this driving mechanism.
Boas is one of the pioneers of functional near-infrared spectroscopy (fNIRS)—a machine that can measure blood flow within the brain with infrared light. It is a flexible, shower-cap-like device that is strapped to a subject’s head and makes measurements through the skull. When someone thinks, speaks or acts, blood rushes to the part of the brain doing the work, and Boas tracks that rush with light. Unlike other brain imaging techniques like magnetic resonance imaging, fNIRS doesn’t require the subject to be completely still; which means it can be used to study brain activity during surgery and memory creation, and on stroke victims, dementia patients and children with autism.
One collaboration, with researchers in BU’s College of Health & Rehabilitation Sciences: Sargent College, is working to understand how the brain of a stroke patient responds to rehab in real time.
One of the successful collaborations that Boas has helped drive is between Assistant Professor Lei Tian (ECE), whose expertise is in computational microscopy and imaging, and signal processing, and Assistant Professor Ian Davison (biology), who works to understand the neural circuits of perceptions and behaviors related to smell. Boas recognized the natural pairing as Davison was developing a miniaturized version of a device called a miniscope, which can image a mouse brain.
Current technology can look at the entire top surface of a mouse brain, but those mesoscopes are much larger and require the mouse to be secured while researchers image the brain working and signaling. Their version of the mesoscope miniaturizes the device and allows the mouse to freely move around while wearing it.
“It’s really about incorporating all these different pieces,” says Tian. “First, there is the scale in terms of the field of view you can image and also the size of the device, which is where my expertise comes in. Second, Boas’ lab has developed this highly specialized surgery to fit the mesoscope to the mouse’s head and have it behave as though the device isn’t there—which is very hard. Then once you have that, you want this mouse to do something and gather data that you need to interpret. That’s where Davison comes in.”
Being able to image the brain while it is actively working, whether in a human or an animal, is a valuable area of study that researchers are just beginning to break into. Device development has been the biggest hindrance to progress, which is why it is such a large focus of the Neurophotonics Center’s work.
Boas has been working to develop fNIRS for years, and not only the device, but also the software which makes it easier for researchers to interpret the results. Software development allows researchers like those in Sargent College to use fNIRS without extensive training on analyzing the neuroimaging results.
“We all need to be well regarded in our disciplines, but if that’s all we know, it’s also a limitation,” says Bishop. “An electrical engineer has a certain box of tools. And if the problem at hand requires the tool you have, great. But if you’ve got a box of screwdrivers and to solve the problem you need a wrench, and your discipline hasn’t ever given you a wrench, what are we going to do about that?”
Multidisciplinary research is like reaching into someone else’s toolbox to solve your own problem. And interdisciplinary research, Bishop says, involves creating a new set of tools that wouldn’t be in any of their own toolboxes.
Chen says that there are many times he needs to turn on a specific gene in a cell, but can’t figure out how or the best way to do it. “Sometimes I’ll just go down to Khalil’s office to hash out the issue and ask if there’s away he knows how to do this,” says Chen. And many times Khalil will have a tool or a graduate student who is working on a related problem who can help. Then another member of the BDC, Assistant Professor John Ngo (BME), might chime in to say he is working on a method to turn on that gene with light, which means Chen could target specific cells.
A conversation with a colleague could spark an idea for a solution to a question—which is why all of the centers work to regularly gather their members and collaborators. Most members of the BDC are housed in the same building—the Rajen Kilachand Center for Integrated Life Sciences & Engineering, which opened last year. In addition to having state-of-the-art labs and facilities, this physical space keeps the team in close proximity, facilitating easy interaction among researchers and students.
“It turns out that even with the telephone and the internet, that human beings’ interaction with each other falls off exponentially with distance, and that’s about 100 meters,” says Bishop. “I interact with people on this floor 10 or 100 times more effectively and more often than the people even 100 meters down the road. People who are kilometers away might as well be on Jupiter as for how I interact with them. The skinnier the pipe that we’re forced to interact through, the less useful information we get, and the more unlikely we are to brainstorm or do innovative thinking.”
Although each center housed within the College of Engineering focuses on a specific area of research, the common thread that ties them all together is developing a deeper understanding of their piece of the world. And to fully comprehend a process as complicated as how the human body grows heart tissue, or how a healthy or a diseased brain works, requires minds from diverse backgrounds and training.
Heart tissue is highly metabolic, it has large mechanical changes in volume and shape when the heart beats, the tissue needs lots of blood flow in order to work—and it’s also electrical. Building this type of tissue has serious chemical, mechanical and electrical challenges, and all of those pieces have to fall into place at the same time.
“One of the reasons we wanted to focus our efforts on heart tissue is that it’s one of the most profound technical challenges,” says Bishop. “But it’s also the number-one killer of people in the United States. And so it’s the hardest technical problem from a tissue engineering point of view, but it’s also the one that, when we solve the problem, will make the biggest positive impact on human health and longevity.
“I think the great research universities like Boston University have a moral obligation to work on the great problems,” says Bishop. “We’re lucky enough to live very comfortable lives and I think that comes with the responsibility to focus on some of the big, important problems, which fundamentally require interdisciplinary research.”