Engineering

BU ENGineer Spring 2017 Magazine

~ saracody ~ Leave a comment

I served as the lead writer and managing editor for the Fall 2016 issue of ENGineer magazine.

Notable writing credits:

  • Page 3-4: “Study Supports Final Pivotal Trial of Bionic Pancreas”
  • Page 6: “NSF Grant Funds Neurophotonics Program”
  • Page 7: “ECE Symposium Honors Career of Professor Emeritus Theodore Moustakas”
  • Page 8: “Khalil Honored with Presidential Early Career and NIH New Innovator Awards”
  • Page 9: “BU Teams Earn Top Honors at iGEM Jamboree”
  • Page 10-21: “Cover story: Greater Than the Sum of Their Parts”
  • Page 22-23: “Small Problem. Big Solution.”
  • Page 23-24: “Time on Her Side”
  • Page 26: “An Internet of Cars”
  • Page 27: “Two Faculty Members Elected to BME Society Leadership,” “ENG Faculty Elevated to Prestigious Fellowships”

How to Hack a Cell

~ saracody

Wong’s New Platform Makes It Easier to Program Living Cells

The human body is made up of trillions of cells, microscopic computers that carry out complex behaviors according to the signals they receive from each other and their environment. Synthetic biologists engineer living cells to control how they behave by converting their genes into programmable circuits. A new study published by Assistant Professor Wilson Wong (BME) in Nature Biotechnology outlines a new simplified platform to target and program mammalian cells as genetic circuits, even complex ones, more quickly and efficiently.

“The problem synthetic biologists are trying to solve is how we ask cells to make decisions and try to design a strategy to make the decision we want it to,” said Wong. “With these circuits, we took a completely different design approach and have created a framework for researchers to target specific cell types and make them perform different types of computations, which will be useful for developing new methods for tissue engineering, stem cell research and diagnostic applications, just to name a few.”

Historically, engineered genetic circuits were inspired by circuit design in electronics, following a similar approach using transcription factors, proteins that induce DNA conversion to RNA, which is tricky to work with because it’s hard to predict an entirely new strand of genetic code. Mammalian cells are especially tricky to work with because they are a much more variable environment and express highly complex behaviors, rendering the electronics approach to circuit design time consuming at best and unreliable at worst.

Wong’s approach uses DNA recombinases, enzymes that cut and paste pieces of DNA sequences, allowing for more targeted manipulation of cells and their behavior. The result is a platform named “BLADE,” or “Boolean logic and arithmetic through DNA excision,” referring to the computer language the cells are programmed with and the computations they can be programmed to carry out. BLADE will allow researchers to use different signals, or inputs, in one streamlined device to control the outputs, or behaviors, of the cells they target.

“The idea was to build a system simple and flexible enough that it can be customized in the field to get any desired outcome using one simple design, instead of having to rebuild and retry a new design every time,” said Benjamin Weinberg, graduate student in Wong’s laboratory and first author on the paper. “Essentially, with BLADE, you can implement any combination of computations you want in mammalian cells. For this particular paper, we might not have built the particular behavior you need, but we wanted to illustrate that using BLADE, you should be able to build the circuit you need to fulfill the behavior you are looking for.”

The paper published in Nature Biotechnology outlines over one hundred examples of circuits that were successfully built using the BLADE platform. Weinberg noted that the researchers intentionally built complex circuits with complicated functions to illustrate the possibilities using their design, including some that program human cells to add or subtract numbers. He uploaded the design plans to an open-source online repository so that other researchers could begin downloading the tools to use in their projects immediately. Weinberg will continue to refine the technology and incorporate into a software program to make it even easier to use, while Wong plans on using the platform to explore medical diagnostic applications.

“Before BLADE, any one of these circuits would have taken several years to build and make functional and then you would have to use trial-and-error to make it work the way you want it to,” said Wong. “I have been doing synthetic biology research for 15 years and I’ve never seen such a complex circuits work on the first try like with this platform. We’re excited to get it out there so people can start using it, and we’re excited to see what they come up with.”

Boston University College of Engineering

Appears on: BU ENG Website, BU Research

Duan Receives NSF CAREER Award

~ saracody

Research and Outreach will Focus on Carbon Nanofluidics

Assistant Professor Chuanhua Duan (ME, MSE) netted a prestigious National Science Foundation (NSF) Faculty Early Career Development (CAREER) award in recognition of his outstanding research and teaching capabilities. He will receive more than half a million dollars over the next five years to pursue high-impact projects that combine research and educational objectives. Duan’s research will focus on developing an understanding of the fundamental mechanisms that affect the flow of water and ions through nanoscale graphene conduits.

“This exciting project is at the intersection of fluid mechanics, nanotechnology, and materials science,” said Professor Alice White (ME, MSE), chair of ME. “It will inform the design of novel nanoporous membranes with impact on some of the world’s largest challenges.”

Graphene, a flexible sheet of pure carbon one atom thick, is a material that allows surprisingly easy passage for liquids and ions with high selectivity. Graphene sheets can be stacked horizontally to form channels, called graphene nanochannels, or rolled into carbon nanotubes. These structures could potentially be used for water desalination, improving the efficiency of batteries and fuel cells, lab-on-a-chip technologies and other biomedical applications. However, when researchers have tried to repeat experiments, large discrepancies in the data attributed to variables such as curvature, ion density, and membrane structure have resulted.

To address this challenge, Duan will use his NSF CAREER award to study water and ion transport in single graphene nanochannels and single carbon nanotubes with different sizes, surface properties, and substrate materials.  He will also perform molecular dynamics simulations to elucidate underlying mechanisms revealed by his experimental studies.  Using this combined experimental-computational approach, he expects to achieve a complete understanding of mass transport in carbon nanofluidic conduits.

“My lab has developed a novel technique, inspired by capillary flow, to accurately measure water and ion transport in a single carbon conduit,” said Duan. “To fully understand the effect that each variable has on the process and resolve discrepancies in previously reported results, this level of accuracy is key.”

In addition to the research component of his CAREER project, Duan will fulfill the educational objectives by creating a module to teach carbon nanofluidics to K-12 students for the Technology Innovation Scholars Program (TISP). In addition, Duan will work with an animator to develop a cartoon that depicts fast-mass transport in carbon nanofluidics using anthropomorphized molecules.

“For example, in one scene we will show water molecules wearing ice skates to demonstrate how easily they slip down the smooth walls of the carbon nanotubes,” said Duan. “Since I know the transport process well, if I can help them visualize that process with something that is familiar, it makes learning about it more accessible.”


Boston University College of Engineering

Appears on: BU ENG Website, BU Research

Forging a New Path

~ saracody

New Outreach Initiative will Educate Community about Synthetic Biology

After a morning of composing DNA out of play dough and learning about genetically engineered mosquitos, the group of high school students put their heads together to solve an age-old question for Bostonians: how do we clean up the Charles River? Proposing solutions like programming microbes to eat toxins and simultaneously synthesize beneficial molecules, it was clear the group of students drew on everything they had learned earlier that day to find a solution using a relatively new field of study: synthetic biology, or engineering living systems.

When the National Science Foundation awarded the Living Computing Project, spearheaded by Associate Professor Douglas Densmore (ECE), a $10 million dollar grant to facilitate synthetic biology using computer engineering, one of the stipulations was an outreach component. The idea was to get research out into the community that is unfamiliar with the field of synthetic biology and foster a career readiness pipeline to the synthetic biology workforce. But Densmore wanted to take it even further than that.

“The NSF grant for the Living Computing Project has a five year research agenda, but we wanted to create an outreach program that would outlive it,” says Densmore. “STEM Pathways aims to formalize the outreach efforts and make it easier to funnel people to the right resources if they exist, and to create them if they don’t. Any individual has a low bandwidth working alone, but with a united effort, you can have a bigger impact.”

STEM Pathways held its inaugural launch event, the Mini-Jamboree, on Feb. 11 when high school students, parents, undergraduates and educators came together for a day of interactive activities to learn more about the field of synthetic biology and how it can be used to solve real-world problems, both globally and locally. According to Tiffany E. Grant, the program coordinator, this is the first of many events that STEM Pathways hopes to host for students of all ages.

“Events like the Mini-Jamboree will expose young people to this exciting new industry and show them how it can improve society,” says Grant. “Our four power words are ‘inspire, mentor, train and empower,’ and the vehicle of choice we are using to strengthen and inform our community is synthetic biology.”

STEM Pathways will follow a three-prong approach to begin a cycle of long-term exposure to the field of synthetic biology, starting with high school students. By providing opportunities to participate in synthetic biology-related activities and providing resources to educators to include in their curricula, awareness will begin at a much earlier age. Undergraduates will have the opportunity to participate in synthetic biology research, mentoring and other educational opportunities to prepare them for careers in the field.  STEM Pathways will also tap industry leaders to establish partnerships for networking, career readiness development, and other resources.

“Not only is this initiative aligned with the mission statement of the College, but also it is addressing a national need to create a more diverse, informed workforce,” says Assistant Dean for Outreach and Diversity Gretchen Fougere. “Synthetic biology is a cutting-edge interdisciplinary field and to understand and develop this technology, it’s important to develop a long term plan that follows students from high school to college and beyond in order to strengthen the field and its potential.”

One of the flagship events for STEM Pathways for both high school and college students will be the iGEM Jamboree, the world’s premier synthetic biology competition for students that hosted more than 5,600 participants from 42 countries last year. Teams of students conduct research up until the competition, where they present their projects for prizes. Even though iGEM is based in Cambridge, there are no local high school students represented in the competition. While BU already has two undergraduate teams in place, Densmore wants to create an opportunity for local high school students to participate in the Jamboree as well, which will allow undergraduates to become mentors to younger students.

“The field of synthetic biology not only needs talented scientists but also more considerate citizens who have a deeper understanding of the field and the potential it has for innovation,” says Divya Israni, a graduate student in Assistant Professor Ahmad Khalil’s (BME) laboratory who serves as a team mentor for BU’s iGEM teams. “It’s an opportunity to open a connection to allow undergraduate students to affect the community outside of BU.”

Boston University College of Engineering

Appears on: BU ENG Website

Study Supports Final Pivotal Trial of Bionic Pancreas

~ saracody

Damiano Nets $12M in Supplemental NIH Funding to Move Forward with Trial

On the heels of winning $12 million in supplemental funding from the National Institutes of Health (NIH) to conduct a major, multi-center, national clinical trial of his iLetTM bionic pancreas, Professor Edward Damiano (BME) has co-authored a study in The Lancet that affirms the technology’s effectiveness in managing type 1 diabetes (T1D) better than current conventional methods.

“This award provides us with significant resources to collect the final clinical data required by the US FDA for regulatory approval, which will pave the way for us to bring the bionic pancreas to market,” says Damiano.

The study was conducted with Damiano’s long-time clinical partner Steven Russell, MD, PhD, at Massachusetts General Hospital (MGH), along with clinical partners Bruce Buckingham, MD, at Stanford University, John Buse, MD, PhD, at the University of North Carolina, and David Harlan, MD, at the University of Massachusetts. It tracked adult T1D patients over two 11-day periods, one using the bihormonal bionic pancreas (which dispenses the hormones insulin and glucagon as needed) and the other using the conventional insulin pump therapy for diabetes management. On days when patients were on the bionic pancreas, their average blood glucose levels were significantly lower compared to their standard treatment, and they reported fewer episodes of hypoglycemia (low blood sugar). The bionic pancreas performed even better overnight, which is a period of particular concern for people with T1D.

“Patients with type 1 diabetes worry about developing hypoglycemia when they are sleeping and tend to let their blood sugar run high at night to reduce that risk,” says Russell. “Our study showed that the bionic pancreas reduced the risk of overnight hypoglycemia to almost nothing without raising the average glucose level. In fact, the improvement in average overnight glucose was greater than the improvement in average glucose over the full 24-hour period.”

The results of The Lancet study are promising, especially as Damiano and his colleagues move forward with conducting the final pivotal clinical trials under the $12 million funding from the NIH, supplementing a previous $1.5 million award he received in 2015. The nine-month trial will test the safety and efficacy of the bihormonal bionic pancreas in adults with T1D, a crucial step in the medical device approval process. Additional funding is being sought to extend this study to the pediatric population and to fund a separate final pivotal trial to test the safety and efficacy of the insulin-only configuration of the iLet bionic pancreas in adults and children with T1D.  The researchers are also seeking funding to conduct separate studies to test the safety and efficacy of the insulin-only and glucagon-only configurations of the iLet bionic pancreas in people with other glycemic control disorders such as type 2 diabetes, hyperinsulinism, insulinoma and many others.

Soon after his son, David, developed T1D as an infant almost 17 years ago, Damiano began working with his team on the bionic pancreas. The technology that they have developed optimizes blood sugar levels by using their mathematical dosing algorithms to automatically calculate and precisely dispense two hormones every five minutes: insulin, when blood sugar levels are high; and glucagon, when they are low. When he and his clinical collaborators at MGH began human trials nearly nine years ago, the tests were done in a hospital setting using a laptop-based system. They switched to their iPhone-based system nearly four years ago, and began trials outside of the hospital in diabetes summer camps in children and in the home-use setting in adults.  Over the past three years, they have been developing their iLet bionic pancreas platform, which integrates all of the components of their iPhone-based platform into a single, compact, handheld device, which is about the size of the original iPhone. The two chambers within the iLet house one vial of insulin and one of glucagon, or just one or the other depending on how the iLet is configured.

“The iLet really is three devices in one, and is flexible enough to treat different chronic conditions of glycemic dysregulation,” says Damiano. “But obtaining the appropriate approvals for those other uses will require additional trials, so we will continue to work on securing funding for those indications.”

Damiano’s goal of providing an easy-to-use, safe, and effective system to help his son and others with T1D now seems within reach. Whereas the final pivotal trial for the bihormonal configuration of the iLet won’t begin recruiting participants another 18 months or so, Damiano hope to begin recruiting participants for the final pivotal trial for the insulin-only configuration of the iLet in about a year. David will begin his freshman year at BU in the fall of 2017, and while Damiano had long hoped that David would head off to college with a bionic pancreas, he now knows that he will fall short of achieving that goal by about a year.

“The reality is, David probably won’t get the iLet until his sophomore year at BU, and even then, he’ll have to start with the insulin-only configuration because the bihormonal configuration won’t be ready until his junior or senior year,” says Damiano. “However, whenever I reflect upon this, I also remind myself that practically every aspect of our endeavor is truly unprecedented – it’s an experiment in the making – so if it takes an extra year or two to get it right on balance, I think it will be worth it.”

Boston University College of Engineering

Originally published on January 4, 2017

Appears on: BU ENG Website