BOSTON UNIVERSITY BIOLOGICAL DESIGN CENTER Annual Report | 2023
Boston University Biological Design Center Annual Report 2023 79 Turning Trash into Medicines, Machine Oils, Cosmetics, and More Title Front cover photo: PhD student Lianne Cohen examines specimens under the stereoscope in the Zeba Wunderlich Lab 1 | Executive Summary 2 | About the Center 4 | Highlights of FY2023 7 | Research Spotlights 14 | Leadership & Staff 16 | Faculty 22 | Fellows & Trainees 24 | Achievements & Awards 26 | Events 30 | Outreach Spotlights 69 | How to Engage with Us Immune Cells Engineered to Battle Cancer Can Be Turned “On” or “Off” Spotlights 979 Title OUTREACH Building a STEM Research Pipeline 9 TRAINING Building a STEM Research Pipeline
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4 | BOSTON UNIVERSITY BIOLOGICAL DESIGN CENTER THE BIOLOGICAL DESIGN CENTER (BDC) brings together expertise from across multiple disciplines at Boston University – including engineering, biology, physics, and chemistry – to build a vibrant community that conducts groundbreaking research in biological design and sets the standards for education and training in synthetic biology. Biology has been a discipline largely based on observation, dissection, and classification of the natural world – however, the field is now poised to become predictive, “engineerable,” and much broader in scope. To understand the processes that define life and to unlock the underlying design logic of biological systems, we must first understand how the component “parts” come together to create complex structures with diverse capabilities. By using forward-engineering technologies such as cellular engineering, 3D printing, and synthetic biology to build biological devices and systems from simple components (molecules, cells, extracellular materials, etc.), researchers at the BDC elucidate the design principles that are important for achieving biological function, thereby complementing and augmenting the traditional deconstructionist approaches. Our researchers also foster unconventional mixing and matching of disparate research areas to create disruptive ideas and biomedical technologies, drawing in scientists from industry and academia alike to tinker, invent, and discover under the center’s auspices. EXECUTIVE SUMMARY The major goals and associated accomplishments of the BDC this past year were to: Expand and mature training programs supporting the BDC mission. We continue to build and enhance the SB2 Training Program and the Kilachand Multicellular Design Program (MDP). In prior years, significant effort had been directed toward establishing the administrative and facility infrastructure, building the community, and developing the research programs associated with these two programs. We have used—to great success—the new training paradigms supported in these two programs to attract world-class graduate students and post-doctoral fellows, particularly those who work at the intersection of multiple disciplines and who foster exciting collaborations across BDC faculty. • This fall, four new second-year Ph.D. students were on-boarded as T32 trainees. A total of 22 Ph.D. students —12 women; seven URMs—have been supported by the SB2 training grant to date, three of whom recently graduated with their Ph.Ds. We recently submitted a renewal application to the NIH/NIGMS, requesting support for eight NIH-supported trainees each year and four BU- supported trainees each year. If our request is approved, our Training Program would support 12 total trainees across two cohorts: six second-year Ph.D. students and six third-year Ph.D. students. • A total of 11 graduate student and four post-doctoral Kilachand Fellows—ten women; two URMs—were supported by the Multicellular Design Program in FY2022. All Kilachand Fellows are co- supervised by two faculty, allowing us to support 16 faculty in these collaborative projects. • In addition to these two training programs, we were recently notified that the NSF NRT proposal entitled NRT-URoL: A Convergent Training Program on Biological Control – led by Elise Morgan (PI), Mary Dunlop, Mo Khalil, & Chris Chen – was funded. We hope to leverage the infrastructure and experiences from our existing training programs to make this new NRT a resounding success.
ANNUAL REPORT 2023 | 5 better photo (long, thin) Integrate new faculty hires into the BDC community. Early engagement is particularly important and a priority for the BDC. All BDC activities are well-advertised via the BDC listserv and in the buildings and communities outside of the Kilachand Center, ensuring that faculty members and their graduate students and post-doctoral fellows have multiple opportunities to interact with BDC researchers and faculty across building locations. We have expanded the BDC faculty by two during this past year, resulting in 19 tenure- track faculty appointed in the BDC. • The Convergent Search in Biological Design yielded the hiring of Professor Samagya Banskota, who will arrive in January 2024 and will have wet lab space in CILSE. • Professor Juan Fuxman Bass recently joined the BDC. Nurture a vibrant community through the development of seminars, courses, and outreach programs for our researchers, industry partners, and other academic colleagues. The BDC has expanded the scope of its seminar series, simultaneously offering professional development and networking opportunities for trainees while continuing to bridge the gap between academia and industry. We invite the broader BU community (i.e., non-BDC trainees in BME, BI, Biology, Chemistry, GWISE, etc.) to participate in most of our professional development activities and all of our internal and external seminars. In FY2022, we hosted: • 12 external seminar speakers, including the eight researchers that gave talks to our community as part of the Convergent Faculty Search in Biological Design • numerous internal research seminars, as well as talks from Ph.D. scientists from non- academic career paths in our Bagels & Bios and SB2 Monthly Meetings. The BDC also continues to support two student-run organizations: • BDC SPIN (Student Program for Industry Networking) is a student-organized mentoring program that prepares trainees for an academia-to-industry transition during graduate school. • The BDC Comm Lab supports a team of graduate student mentors that help their peers improve their writing, presentation, and visual design skills. • We are currently helping both initiatives expand their activities and identify new graduate students who may want to join their leadership teams (thereby ensuring that the groups will continue to run after the more senior members graduate). Foster a culture of deep collaboration between BDC labs, by alerting faculty members to funding opportunities and helping them write multi-PI grants. The BDC currently has • 11 multi-PI research grants from external sources (three of which started in FY2022) • two multi-PI training grants from external sources (one of which started in FY2022) • three multi-PI grants from internal sources Elevate BDC science in the local and national scientific community. We have worked hard towards our goal of growing our extended network and placing the BDC firmly on the map of leading centers for biological design and biotechnological advancement. To this end, we have undertaken extensive STEM Outreach and Education activities through our STEM Pathways program and will publish our first external facing ‘BDC Annual Report’ this winter. We have also created BDC Travel Grants for our trainees: $7,000 was distributed to 12 graduate students and post-doctoral fellows to attend conferences this past summer, and we will be sending out another call for applications this winter. Caption
6 | BOSTON UNIVERSITY BIOLOGICAL DESIGN CENTER ANNUAL REPORT 2023 ANNUAL REPORT 2022 | 6 Caption
ANNUAL REPORT 2023 | 7 AS ALL GREEN-THUMBED GARDENERS KNOW, rotting fruits and vegetables—gnawed-on apple cores, discarded potato peels— are a precious resource. Let them bubble away in a composter and they become a nourishing food for flower beds and vegetable gardens. Engineers know it too. The nutrients produced by decaying food can also be used in biomanufacturing, helping fuel bioreactors, devices that can synthesize new substances. Instead of smokestacks pumping toxins into the atmosphere, biomanufacturing makes use of naturally occurring microorganisms and processes, like those generated by rotting food scraps, to make everything from medicines and gene therapies to cleaner and greener materials, machine oils, detergents, fuels, fabrics, fragrances, and even foods. It has the potential to revolutionize industry while dramatically cutting carbon emissions. But in the United States in particular, the biomanufacturing sector needs to grow significantly, especially if we’re to avoid supply chain disruptions and security breaches. At the Boston University College of Engineering, a crossdisciplinary trio of researchers is helping to make a smarter, more efficient bioreactor. They’re part of a team that was recently awarded a $3 million grant from Schmidt Futures, funding given in partnership with bioindustrial manufacturing consortium BioMADE and as part of a federal push for more and better bioreactors. The BU engineers— Ahmad (“Mo”) Khalil, Rabia Yazicigil, and Douglas Densmore— are collaborating with experts from Capra Biosciences, Inc., a start-up behind a cutting-edge bioreactor technology. Capra’s bioreactor—known as a continuous flow device—uses biofilm, essentially a layer of slime hospitable to bacteria. They’ve already used it to create a petroleum-free skin cream and plan to turn it to producing biological, rather than petrochemical, lubricants for motors and other machinery. But refining and replicating the company’s innovative platform on a grand scale will require automation and novel quality-control and security measures, which is where the BU team—with backgrounds in genetic engineering, electronics, and automation—comes in. “This kind of convergence of disciplines is amazing. It is the future in terms of where advances in biotechnology are coming from, and BU is definitely at the forefront,” says Capra cofounder Andrew Magyar. “We want to engineer organisms to help us make products sustainably and costRESEARCH SPOTLIGHTS Turning Trash into Medicines, Machine Oils, Cosmetics, and More A multidisciplinary team of BU engineers is helping build a next-generation bioreactor to turn food scraps into greener, cleaner manufactured products ENG researchers Rabia Yazicigil (from left), Mo Khalil, and Douglas Densmore are collaborating on a more efficient bioreactor. Photo by Dana J. Quigley
8 | BOSTON UNIVERSITY BIOLOGICAL DESIGN CENTER competitively, so consumers won’t have to decide, ‘Do I want the sustainable option or the cheap option?’” The BU team has already proposed an ingenious series of design solutions that will allow the company to turn an unpredictable jumble of food, manure, and other waste products into a reliable final result, as well as monitor the whole process with tiny sensors that can float in a bioreactor. They also have a plan for allowing other researchers nationwide to adapt their work and create replica bioreactors producing multiple life-changing, and planet-saving, products in a vast range of fields. Transforming Waste Khalil began his career as a mechanical engineer, but today he is better known as a pioneer of synthetic biology. In particular, his team builds molecular “circuits,” and they have translated these insights into gene circuit engineering platforms that enable the programming of human cells, such as immune cells, for a new generation of cellular therapies that might one day be used to combat diseases such as cancer. “We like to ask the simple yet bold questions, ‘What if we built it?’ and ‘What can we learn from this process?’” says Khalil, an ENG professor of biomedical engineering. “That inverse approach to the study of biology forces one to question prevailing assumptions, and it can lead to surprising results.” Khalil, who also serves as an advisor to Capra, is the inventor of a small-scale bioreactor system called eVOLVER, a customizable, automated platform that can remotely monitor and manage hundreds of cell cultures—when researchers grow cells in a controlled environment—in real time for a variety of applications. Now in use in more than 50 universities, this DIY open-source system is infinitely adaptable, allowing researchers to create custom microbial experiments. One of Capra’s objectives is to develop new methods for working with complex waste-based feedstocks—the material left over after bacteria break down manure and food scraps that gets fed into a bioreactor—but a challenge with that kind of material is variability in its makeup. By running a slew of experiments with eVOLVER, Khalil aims to rapidly optimize the process, allowing different types of waste-based feedstocks to turn out a consistent level of product—in this case, retinol (vitamin A) to start with. Khalil is also adapting his invention for the project—adding custom parts to help precisely control fluid flow and culture conditions. “By the end of 18 months, we want to have a fully automated biofilm reactor pilot plant that can continuously produce more than one kilogram of vitamin A per day,” says Yazicigil, an ENG associate professor of electrical and computer engineering. Monitoring Progress and Ensuring Security Yazicigil’s expertise is in electronics, but she is more than a dabbler in biology. Some of her recent work includes designing an ingestible capsule that monitors gut health with the aid of a tiny sensor that runs on ultralow power. She’s adapting that technology to produce sensors that will float inside the bioreactor and measure the levels of PH, oxygen, glycerol, lactate, and various organic acids. The sensors will even evaluate the electric potential of the biofilm. “Traditionally, bioreactors are monitored with bulky instruments or complex probes that have to be inserted in holes in the lid or side,” Yazicigil says. By contrast, her Mo Khalil’s eVOLVER is an automated platform that can remotely monitor and manage hundreds of cell cultures in real time for a variety of applications. Photo by Dana J. Quigley “We like to ask the simple yet bold questions, ‘What if we built it?’ and ‘What can we learn from this process? That inverse approach to the study of biology forces one to question prevailing assumptions, and it can lead to surprising results.” - Mo Khalil
ANNUAL REPORT 2023 | 9 tiny sensors, running on mere nanowatt-level power, will wirelessly transmit the measurements in real time, allowing technicians to adjust the flow of nutrients as needed. A crucial part of her task is making the communications secure, Yazicigil says, and her team is working with Capra to make security integral to the sensors. “We need to protect against communication attacks, like eavesdropping, or jamming attacks, which would impact communication between the sensors and the hub,” she says. “I have to tailor the sensor chips to fit the system needs of this bioreactor technology. It’s an exciting project. It involves start-ups, academia, biomedical and electrical and computer engineering. It’s powerful to bring these all together.” Scaling Up, Sharing Breakthroughs To truly scale up the modified bioreactor, the operation will also need to take advantage of BU’s Design, Automation, Manufacturing and Processes (DAMP) Lab, led by Densmore, an ENG professor of electrical and computer engineering. He’s been working in synthetic biology research since 2007 and has expertise in developing electrodes for microfluidics and robotics for high-throughput testing. The heavily automated DAMP Lab offers accelerated services such as DNA cloning, bacteria growth, and RNA sequencing for faster research results in synthetic biology. It recently did double duty as a major part of BU’s award-winning Clinical Testing Laboratory, which processed up to 6,000 COVID tests of faculty, staff, and students per day during the pandemic. Now, the lab is getting ready to run biofilm-focused experiments on several eVOLVERs at once. For Densmore, the product is not (or at least not only) retinol, but the process itself. By sharing the BU team’s results, technical reports, and methods with the other 140 members of the BioMADE consortium, Densmore will be helping to propagate a replicable system for converting all sorts of bio-based feedstocks into all manner of useful products. Replicability is key, Densmore explains. To tackle global challenges from cancer to climate change, he says, “we need more eyes on these problems. To do that, we need to lower the barrier to entry—but safely. So, we centralize the manufacturing infrastructure,” within a certain number of certified labs like BU’s, “and distribute the computational infrastructure.” To start with, BioMADE researchers will remotely order up experiments, and Densmore and his team will carry them out. In the longer term, Densmore envisions members of the research community at large downloading the DAMP Lab’s software, as well as the list of hardware used and assembly directions, to build their own bioreactors. “That’s how we democratize biology with computing,” he says. Instead of hoarding its secret sauce, as Densmore puts it, BU in a sense will franchise the DAMP Lab, standardizing equipment, software, and processes all over the country. But because BU’s bioreactor solution is infinitely adaptable, those replica labs won’t be producing identical studies and products. Other researchers will apply their creativity and generate their own solutions. Using one more food analogy, he points out that most people don’t bake their own bread, because it’s simply not an efficient use of their time. But in biology, too much time is sunk into tasks that would be better automated and standardized, freeing researchers to use their minds. “Pragmatically, that’s the only way to advance science and society,” Densmore says. “Right now, biology is baking a lot of bread.” By making BU’s packaged sliced bread available everywhere, “I’m saying, ‘Let’s get to making some cool sandwiches.’” * * * This article, authored by Patrick Kennedy, originally appeared in The Brink on June 15, 2023. To read the original article visit: tinyurl.com/mpu6p5hy The novel chip Rabia Yazicigil has designed will enable tiny wireless sensors floating in the bioreactor. Photo by Rabia Yazicigil “I have to tailor the sensor chips to fit the system needs of this bioreactor technology. It’s an exciting project. It involves start-ups, academia, biomedical and electrical and computer engineering.” - Rabia Yazicigil
10 | BOSTON UNIVERSITY BIOLOGICAL DESIGN CENTER THE BILLIONS OF IMMUNE CELLS that help protect us from diseases do amazing things, but sometimes they need a little boost. For decades, scientists have been trying to figure out ways to engineer living immune cells to better combat aggressive diseases, like cancer. One big, relatively recent advancement in the fight against cancer is CAR T-cell therapy, a treatment that involves modifying immune cells called T cells, microscopic powerhouses that take on infections. Scientists have figured out a way to remove T cells from a person’s blood, insert a special kind of gene called a receptor, which binds to cancer cells, and transfer the engineered T cells back to the patient. This type of receptor—a chimeric antigen receptor, or CAR—is tailored to match the specific cancer being targeted and has been found to be effective for treating certain types of cancer, especially leukemia. Once CAR-T cells reenter the bloodstream, they start to replicate and begin their fight. “It is very exciting technology,” says Wilson Wong, a Boston University College of Engineering associate professor of biomedical engineering, who has been studying CAR-T cells for over 10 years. But there are problems with safety, he says, that can make the therapy extremely risky. At times, CAR-T cells overstimulate the immune system, which triggers the release of a substance called cytokine. This can cause a potentially fatal inflammatory condition known as cytokine release syndrome. Other serious complications can include neurological difficulties, or other organs in the body being mistakenly targeted by the immune cells. To make this groundbreaking therapy less risky for patients, Wong and a team of researchers are working to create a safety switch built into the CAR-T cell design. In a new paper in Cancer Cell, the researchers reveal a new type of CAR-T cell that can be turned on or off, making it possible to stop cells from activating before severe side effects occur. Their new system is called VIPER CAR-T cells. VIPER— which stands for Versatile ProtEase Regulatable—cells are engineered so they can be controlled by giving a patient an antiviral drug that disrupts the cell’s activity, lessening the safety concerns that come with traditional CARs. “We see this as the next generation of this type of therapy,” Wong says. In all CAR-T cells, part of the receptor sticks out of the cell membrane, while part of it is inside the cell. The part sticking outside of the membrane binds with cancer antigens, which then activates the T cell and destroys the cancer cell. VIPER CAR-T cells have a special protein chain inserted next to the receptor. The researchers created two different systems— one that is switched on at the time the VIPER CARs are transferred back to a patient, and one that is switched off. The two systems work slightly differently, but can both be turned off or on by the patient taking an FDA-approved drug that is typically used for treating hepatitis C. “That is the most exciting part of this study, that the antivirals are already FDA approved,” says Huishan Li, lead author of the paper and a postdoctoral fellow in Wong’s lab and the Khalil Lab. When administered, the drug molecule interacts with the inserted protein chain, kicking off a series of reactions in the cell to make it disengage, or activate, depending on which system is being used. The research team included John T. Ngo, an ENG assistant professor of biomedical engineering, and Ahmad S. Khalil, an ENG associate professor of biomedical engineering and associate director of the Biological Design Center. Scientists have crafted other CAR-T cell systems that are controlled by pharmaceuticals, but this is the first that has two modes of operation—on or off. The two modes can allow doctors to target the cancer more aggressively, since it will be possible to dial down the treatment if necessary, Wong says. Alternatively, if there is any uncertainty, doctors could turn the VIPER CAR-T cells on incrementally. * * * This excerpted article, authored by Jessica Colarossi, originally appeared in The Brink on September 8, 2022. To read the full article visit: tinyurl.com/3vn87yaf Immune Cells Engineered to Battle Cancer Can Be Turned “On” or “Off” Researchers at BU develop a safety system for edited T cells that could make cancer treatment safer and more effective T cells, a type of white blood cell that defends the body from invaders, can be modified by scientists to attack cancer cells. Researchers at Boston University are developing a way to make this cancer treatment safer for patients. Photo by cgtoolbox/iStock
ANNUAL REPORT 2023 | 11 GREATER BOSTON HAS BECOME the nation’s biotech hub—the Silicon Valley of life sciences, according to some— and Massachusetts is now reportedly home to more than 1,000 biotech companies, employing more than 80,000 people. One of the newest multimillion-dollar firms helping to drive the boom has its roots in a Boston University lab. Satellite Bio—fueled by technology codeveloped by BU biomedical engineer Christopher Chen—launched in April after announcing it had secured $110 million in venture funding. The company promises to pioneer “the next frontier of regenerative medicine” by developing tissue implants that can help treat or replace diseased organs. Satellite Bio was cofounded by Chen, a BU William F. Warren Distinguished Professor and a College of Engineering professor of biomedical engineering, and Sangeeta Bhatia of Massachusetts Institute of Technology. The company says its novel technology, which it calls “tissue therapeutics,” would allow scientists to program cells and aggregate them “into novel, implantable therapies, called ‘satellites,’ which can be introduced to patients to repair, restore, or even replace dysfunctional or diseased tissue or organs.” The satellites can either act like a supercharged Band-Aid, helping to speed rehabilitation, or more like a power generator, taking on some of an organ’s typical function to get the body running closer to its optimal level. “It’s a mission-driven organization that we formed to make an impact on people and patients,” says Chen. “There are a lot of different types of diseases where it isn’t a single cell that isn’t working anymore, but is an aspect of an organ that isn’t functioning. There haven’t really been a lot of technologies around having groups of cells or tissue-like structures that can replace tissue-level functions—that’s where we’re coming in.” To start, Satellite Bio will focus on liver disease, which can be especially hard to treat—a transplant may be the only option for those with liver failure. “It’s a space where we think the clinical need is high and that our technology could make an impact,” says Chen. He hopes the company can start clinical trials within a few years and that the work will pave the way for a new category of tissue repair medicines that can treat diseases and conditions of organ failure beyond the liver. Chen’s expertise is in tissue microfabrication, using engineering to figure out how cells form tissues, and then shaping that process. He says it’s his work in vascular bioengineering—or the form and function of blood vessels— that provides one of the foundations for Satellite Bio’s technology: “How do we get a tissue vascularized sufficiently and quickly enough that it will engraft and thrive?” MIT’s Bhatia brings decades of experience in liver and tissue engineering. She and Chen have known each other since graduate school and have remained collaborators, producing a number of joint research papers. Tissue therapeutics, Chen says, is “really a combination of the two pillars—tissue and vascular engineering—that we brought together to try to solve a problem.” Although the company was cofounded by Chen and is based on technology he helped develop, he’s not jumping from BU to help run it. He’ll provide what he calls “highlevel scientific feedback and guidance,” but says it’ll be a two-way street, with Satellite Bio’s work helping to inform his teaching and research. “They can help us learn more about what the real pain points are in taking a technology like this to the clinic, and that gets my team more visibility on the problems we need to do more research on,” says Chen, who heads BU’s Professor Christopher Chen cofounded Satellite Bio, a regenerative medicine company. Photo courtesy of BU Photography. Biotech Developing “Tissue Therapeutics” Launches from BU and MIT Labs Satellite Bio, a regenerative medicine company cofounded by Christopher Chen, has received $110 million in funding
12 | BOSTON UNIVERSITY BIOLOGICAL DESIGN CENTER Biological Design Center and is deputy director of CELLMET, a multi-institutional National Science Foundation Engineering Research Center in Cellular Metamaterials. “From an educational perspective, it impacts how I teach and think about what students need to learn—the scientific problems that need to be solved, understanding the many parts of a company that need to come together to make something work.” The company is also benefiting BU students in another important way: providing a new employment opportunity once they wrap their degrees. One alum already helping push its technology toward clinical trials is scientist Divya Israni (ENG’21), who joined Satellite Bio in its stealth—or fundraising—phase after completing her PhD in biomedical engineering. “Satellite Bio has launched with an audacious mission to restore hope to patients and families suffering from severe, life-threatening conditions,” says Israni. Although Satellite Bio’s launch—and funding level—created a media splash with headlines in the Boston Globe and beyond, Chen says it wouldn’t have been possible without years of BU’s industry relationshipbuilding and the University’s support in protecting intellectual property and commercializing ideas. “You can’t understate how important it is that the University not only supports the mission of making impact in our wider world,” says Chen, “but also really supports faculty and celebrates graduate students not just going into academic sectors, but also going out to companies, trying to take some of these technologies that are developed within universities and making them impactful.” ilitint. * * * This article, authored by Andrew Thurstion, originally appeared in The Brink on May 6, 2022. To read the original article visit: tinyurl.com/bdfdh96b “There are a lot of different types of diseases where it isn’t a single cell that isn’t working anymore, but is an aspect of an organ that isn’t functioning. There haven’t really been a lot of technologies around having groups of cells or tissue-like structures that can replace tissue-level functions—that’s where we’re coming in.” - Christopher Chen Satellite Bio calls its technology “tissue therapeutics” and says it would allow scientists to program cells and aggregate them “into novel, implantable therapies, called ‘satellites,’” which could be used to repair diseased tissue or organs. Image courtesy of Satellite Bio
ANNUAL REPORT 2023 | 13 GREATER BOSTON HAS BECOME tAcimillicient que mi, nulpa doluptur? Qui qui ducium fuga. Se sequi coreperum esectat iisimilis mintus non corro corem aborae es ium doluptatis nus, ne litatae esti tetur? Epere voloritatis sus, consequ iandae doluptate eribus maximolut poreiundae quo dersperum ex et optat quis in el inciam esequia tiandigent omnis inctio iuntiam qui dolent lature nam, sit re volorepe plati officilist eum acearci ureperis doluptin nossita tenimpernam solum que mil ipis destiae magnimenis reperrum quae exernat iberum aut qui a alitatiae ad moditas atium quo quat eos estrum de cor rae vel illessintemo id ullupturi venduci ligendelesse explati aectio. Restiates re, volut maxime nis eum ea sandaec atemquo quias ipiduci totate quis ea nus denia volenis et int pario dolorro blabore pernam incto to id qui reseque vit dolor simin exceprate volupie nditiaspedis archicil eum que quia nonseque moloritas reriori beaturi tenduci isquuntotae. Et omnia dolorem oluptio odi siment ex eate nulparum eroviti busapel iquasit velessequi commos eatat am ut modione velecabor magnatum voluptur sitatis tibus. Untio con core, simoluptae postia dolor sum as molum con porro eos conse nis dus et unt voluptiae pratur? Haruptatem nectet et quatur molupti renihicias qui ulpa perumquis ent doloraerum et adi delis dolessit laciendunt fugia doluptae corrunt et hil iduntium impores tempostrum ipsanim inveliti alignam quiae nectia sapelitae dolorat ibusament. Ullia a dolorei umquam ligenis et, opturer roritios ne ad maximus. Um venit iusam nos est remquas consequas inctem serat est aceperatur, verro beriorum que modisi doluptaque volorectem. Ut et velendis cus doluptatum nobitiaspiet invelit faccum net elignis dolupie nimusape pelles resequosam, ommolupta sin porem autasperum erectur aborum ute aut qui re plitatem endam et assi seque exceperum quataquatis remporrum aut lisquos andel et est pre por ad eostium explia est pratur res mo comnita nihit ario elendel mosam arum velliqu iderest laborecesto esciist eatusci dendant, comnis dolore, et quam harum volupta nobit, volo est, quodicimus, ipsapedit, nat repuditium voluptatur? Soloremqui quodio testionest, earibus. Neque earchita dolor aut re moluptatque id magnatur? Ugit latecto reicilignis etur, seque pre et re laboritatium que vendicate volorro consequas in et eos quid quis eliquidemque cullacestrum quianisquia pro consedicid elignatecto ipic tem que sit landit id mi, sant, acipsapiciis estiassumqui odicabo rerspitium, volorum, saped molesseque plaborerum facest, tetur? Beatiam lit quasperecto doluptatur moluptae. Ihilitae aceaque et ut ad unto moluptas et hariatur alibusc imperup tibusa as qui dit ullupta et esecum quuntem facepratium is adit harciuntem hil ipicid que post aute vel iusandipsame numenis im sunt doles es aut fugit vel ese mil earum siminulpa dia cuptaque nulpa ni berepelibus ducid utet porroviducil milisinis ersperore, ut et endam aut int fugiaspediam idelecea con provitiossum laboriossi voluptata venihil lacium, nonsequo dem nimpore pellatia volorep ratur? Ibusam faccum as evendit et hariberia derum ne consend untore vent. Ipsa sitibusapis soloriae evelendam, alis elenima gnimus con cum que pos quis mo imusament di consendae sapienimus et exerferem fuga. Nem simet volo del inctur molum es rerum ullenis derciis el et dolorempos doluptassi ipsuntu mendigendam, odiatia nturisi restisqui omnit, occum, ut dis velique quis illantem. Et omnis simus rat. Acepelitae magnis provit, conecto taturibus et modio dus vitibus sum audio optatque nihil et optintem venempo rporibus es eium labore quis iur autector sam rerionsequam et ullo tem et reicid mod ut is similluptaes accat vendis ad que volupti qui blateture es endent velictas es doluption eost quation conserrovit, torunt ent evellat quam ea venim qui doles mosam im iusam re ma qui con nihicium voluptatur, cusciam eaquam rem fugite vendam Professor Christopher Chen cofounded Satellite Bio, a regenerative medicine company. Photo courtesy of BU Photography. Ipic tem amus enisquaectio doluptatam ne et ommodi bea dolupicipsum rem con et rem sim Quidunto estiame voloreh endersp idendist, volupic tatemporatur sim ist vollesedi dolum better photo (long, thin)
14 | BOSTON UNIVERSITY BIOLOGICAL DESIGN CENTER quo dolutas moluptas ullat. Amendigendae estint ex ea sinvell uptatem anda nimodig enditatem fuga. Cil ide laboribus doloribea conseque rerro ipit modipsae volupta tionsequam quidesciist, te volorro isitiusam idit quae ventus accus is veristi oreheni magnatu riassit ad quia doluptatis qui ratiandi torum dem ipis magnihil eicimus eos erumquos si remolup tatque preperum nonese voluptis delenimodit erepe nisi dio te sanditae nonseque as nus aut premo odit ped quam soloribus siti consequaeces et utem eossinu llaborae et iusandi tatiustibus quatem ut ut la quataerepudi atentibus nullabor sum am sam consequo mint etur minctatur saniet omnis rehendis aut quiaestium, sequat. Voluptur, est voluptati il ium recusan damusdae ex esenecum quiaereium eatus aut vel inus. Nequia que offictem ernatis aut quae doluptas id et atquamusaes ma commodio mi, nim ea voluptium fugia corepudit vercia sit aut ipsam et lacepudam aut escillorum expelent duntis el moluptature, sin eum et pa sunt pellam re sandam, in niminulles vero blaniminctor sequid quostium delibus estempe reic tem laboreicius plit vel modiossim eserferferia nonsecto tecat. Ut ut assi odis aut eos dolore niat magnihillent aut estis si con planda si dolupici nullore sciliqui deliqua tiumquiatemo dolut unt occus si omnient atio incit est, te et et acient duci nihit fuga. Caboria nditatque volute pa venditatem nit aut vent, corrum quatios niscient, eos nullaccabo. Nam dolenih illaudandi que nonseque sum et quatus voluptatibus maximin nem ellorit ullabore dolo to blatur, omnis qui torendi piciditiae viti illam ex et fugiam, consequam fugit odit, conseque enditibus inullaccum reperio nsequas pictibus enihillam eatia nos imporporit que voluptatia perspitiam re nihilite a dolecea rionsequidus quatur, aut as eum atent faccus si aborpore doluptatur, unt, quidebiti re nectatur? Coratis elia cum vent et resequae pligenet millest, qui sus diciend aerupidio eum nimolorro blacestio. Am, quati occus vit quamus poria sinci od et eium dolorem is magnatem litatum cusame veritiur, tet arcipsum qui odisquidus. “Oluptas ea quam autet aliquassum eosae estius sum untio verepel iur? Faccus, sereium inctibus nonseni veliqui delectas pro dis dolut officte provit essedi doluptates incita ex et am explatur, vollent pre veris dolupid ea dolor rae ernat.” - vollent pre Satellite Bio calls its technology “tissue therapeutics” and says it would allow scientists to program cells and aggregate them “into novel, implantable therapies, called ‘satellites,’” which could be used to repair diseased tissue or organs. Image courtesy of Satellite Bio
15 | BOSTON UNIVERSITY BIOLOGICAL DESIGN CENTER ANNUAL REPORT 2023 | 15 The Biological Design Center occupies several floors of the Rajen Kilachand Center for Integrated Life Sciences and Engineering located on the Charles River Campus at Boston University
16 | BOSTON UNIVERSITY BIOLOGICAL DESIGN CENTER The liver grafts shown here, which contain primary human hepatocytes (magenta) and human endothelial cells (yellow), show promise for treatment of patients suffering from liver disease. This image was developed by PhD student Amy Stooddard in the Tissue Microfabrication Lab run by Christopher Chen. 16 | BOSTON UNIVERSITY BIOLOGICAL DESIGN CENTER
ANNUAL REPORT 2023 ANNUAL REPORT 2023 | 17 hi-res version requested from Amy Stoddard
18 | BOSTON UNIVERSITY BIOLOGICAL DESIGN CENTER Caption ANNUAL REPORT 2023 | 18
ANNUAL REPORT 2023 | 19 LEADERSHIP & STAFF Ahmad S. Khalil Associate Director 617-358-6957 [email protected] Joshua Finkelstein Executive Director [email protected] Christopher Chen Director 617-353-1699 [email protected] Amy Michael Senior Program Coordinator [email protected] Jim Cooney Communications Manager [email protected] Design space, tbd Hailey Gordon Director of STEM Pathways 617-358-6338 [email protected] Dave Michaels Center Administrator [email protected] Outside the BDC staff offices
20 | BOSTON UNIVERSITY BIOLOGICAL DESIGN CENTER PhD student Chris Kuffner working in the John Ngo Lab 20 | BOSTON UNIVERSITY BIOLOGICAL DESIGN CENTER
ANNUAL REPORT 2023 | 21 FACULTY Brian Cleary Assistant Professor of Computing and Data Sciences, Biomedical Eng, Biology, and Bioinformatics [email protected] Christopher Chen Professor, Biomedical Engineering 617-353-1699 [email protected] Samagya Banskota Assistant Professor, Biomedical Engineering [email protected] Alexander A. Green Assistant Professor, Biomedical Engineering 617-353-2805 [email protected] Mary Dunlop Associate Professor, Biomedical Engineering [email protected] Douglas Densmore Professor, Electrical and Computer Engineering 617-358-6238 [email protected] Cynthia A. Bradham Associate Professor, Biology 617-358-5212 [email protected] Juan Fuxman Bass Associate Professor, Biology 617-353-2448 [email protected] Jeroen Eyckmans Research Assistant Professor, Biomedical Engineering 617-358-6258 [email protected]
22 | BOSTON UNIVERSITY BIOLOGICAL DESIGN CENTER Daniel Segrè Professor, Biology, Bioinformatics, and Biomedical Engineering 617-358-2301 [email protected] John Ngo Associate Professor, Biomedical Engineering 617-358-2692 [email protected] Pankaj Mehta Professor, Physics and Biomedical Engineering 617-353-2600 [email protected] Arturo Vegas Assistant Professor, Chemistry, Biomedical Engineering, and Materials Science & Engineering 617-358-2229 [email protected] Trevor Siggers Associate Professor, Biology 617-353-2432 [email protected] Joseph Larkin Assistant Professor, Biology and Physics 617-353-6577 [email protected] Kirill Korolev Associate Professor, Physics 617-358-2506 [email protected] Ahmad S. Khalil Professor, Biomedical Engineering 617-358-6957 [email protected]
ANNUAL REPORT 2023 | 23 Wilson Wong Associate Professor, Biomedical Engineering 617-358-6958 [email protected] Rabia Tugce Yazicigil Assistant Professor, Electrical and Computer Engineering 617-353-2815 [email protected] Zeba Wunderlich Assistant Professor, Biology 617-353-3833 [email protected] The lobby of the Rajen Kilachand building features an art installation titled Blue-Green Brainbow, produced by Brooklyn-based sculptor and printmaker Carson Fox, which was inspired by a neuroimaging technique that distinguishes individual neurons in the brain using fluorescent proteins.
24 | BOSTON UNIVERSITY BIOLOGICAL DESIGN CENTER WITH A COMPETITIVE National Science Foundation Research Traineeship (NRT) award, Boston University is positioning itself to become a major hub not only in the emerging research field of biological feedback control, but also in the training of tomorrow’s engineering biology workforce. “A Convergent Training Program on Biological Control,” co-directed by ENG Dean ad interim Elise Morgan (ME, MSE, BME) and Associate Professor Mary Dunlop (BME), aims to train a diverse group of PhD students—approximately 75 over the next five years—for tomorrow’s workforce in biotech, synthetic biology, manufacturing, robotics, sustainability, and other sectors. The agency announced the award this month. Professors Christopher Chen (BME, MSE) and Ahmad “Mo” Khalil (BME) are PIs along with Morgan and Dunlop. Researchers working in biological control focus on understanding and replicating the remarkable abilities that living systems have to self-regulate and adapt by using feedback to respond to changes in their environment. From salamanders that can regrow a lost limb to bacteria that sense and move toward food sources, examples of feedback control abound in nature. In recent years, researchers have been digging into the complex workings of feedback control as it occurs in nature, with an eye to effecting similar processes artificially. Potential applications include tissue regeneration, sustainable farming, decontaminating polluted water, designing microbes to produce sought-after chemicals in a sustainable manner, and developing assistive devices for the disabled. However, despite all that promise, opportunities to learn feedback control as it applies in biological contexts are limited and ad hoc. Control theory traditionally sits within mechanical and electrical engineering curricula, where there isn’t room to delve into nature’s infinite array of biological control strategies. Meanwhile, biology students don’t typically get trained in the quantitative analysis of feedback mechanisms. To bridge this gap, the BU team has proposed to create, and the NSF is investing nearly $3 million to facilitate, a first-of-its-kind graduate training program in biological control. The NRT program will feature all-new courses, boot camps, workshops, co-mentored research, and industry internships, all geared to advancing both the field of biological control and the position of BU graduates within it. The program will recruit students from underrepresented demographic groups as well as varied academic backgrounds, including mechanical, biomedical, and electrical engineering, biology, physics, chemistry, and data science, among others. Through the integration of the disciplines involved, faculty Dean ad interim Elise Morgan and co-PIs, along with more than a dozen faculty across BU, garnered an NSF grant to train diverse engineers in biological control. Photo by Dana J. Quigley TRAINING SPOTLIGHTS Converging on Training Tomorrow’s Bioengineers Nation’s first training program for biological control workforce wins NSF grant
ANNUAL REPORT 2023 | 25 and students will “develop a common language and shared body of technical skills in the fundamental underpinnings of biological control,” the team wrote in their proposal to the NSF. Moreover, the team expects new discoveries to result from the transdisciplinary research projects, broadening researchers’ understanding and potentially leading to new technologies in areas such as molecular-level control algorithms, microbial feedback control systems, selfpowered hybrid systems that combine living and engineered parts, and advanced robotic systems that can heal and evolve. The NRT award is one of just 22 the NSF granted this year. The program encompasses a wide range of experts from departments and centers across BU, including not only researchers but also participants from the Newbury Center, the Professional Development and Postdoctoral Affairs office, and STEM Pathways. Other ENG faculty involved include Professor Calin Belta (ME, SE, ECE), Professor Douglas Densmore (ECE, BME, MSE), Assistant Professor Andrew Sabelhaus (ME, SE), Assistant Professor Emma Lejeune (ME), Assistant Professor Sheila Russo (ME, MSE), Assistant Professor Tommaso Ranzani (ME), Assistant Professor Michael Albro (ME, MSE, BME), Assistant Professor Brianne Connizzo (BME), and Assistant Professor Jeroen Eyckmans (BME). Other BU faculty collaborators include LaDora Thompson (physical therapy), the Travis M. Roy Professor at the College of Health & Rehabilitation Sciences: Sargent College, as well as Assistant Professor Joe Larkin (biology), Assistant Professor Maria Kamenetska (physics), and Associate Professor Zeba Wunderlich (biology) from the College of Arts & Sciences. “BU ENG’s focus on convergence—bringing people from many disciplines together to work on societal challenges— makes us uniquely positioned to bring the field of biological control from an emerging area to a mature discipline,” said Morgan, who is also the Maysarah K. Sukkar Professor of Engineering Design and Innovation, and director of the Center for Multiscale & Translational Mechanobiology, where the project will be headquartered. “We look forward to educating tomorrow’s leaders in this area and creating a training program that can be replicated at other universities too.” * * * This article, written by Patrick L. Kennedy, originally appeared in the BU Engineering blog on October 4, 2023. To read the original article visit: tinyurl.com/22r83jd7 PhD students Jillian Ness (left) and Lianne Cohen [FILL IN] ... in the Zeba Wunderlich Lab
26 | BOSTON UNIVERSITY BIOLOGICAL DESIGN CENTER FELLOWS & TRAINEES THE CENTER HAS A BUDGET for supporting potential pilot projects and innovative new techniques for research. On the recommendation of the Center executive committee, in FY22 these funds were used to support post-doctoral fellows with expertise in techniques that are central to development of new research areas and associated grant applications. These researchers were designated the Center for Systems Neuroscience Distinguished Fellows. FY22 FELLOWS Dr. Maria Victoria Moya (with Prof. Michael Economo) Developing new optical technology for measuring connections between brain cells (manuscript currently under review); obtained an NIH NRSA F32 postdoctoral fellowship Dr. Gary Kane (with Prof. Benjamin Scott) Using wide field imaging to analyze neural mechanisms underlying the optimization of decisionmaking Dr. Brenna Fearey (with Prof. Mark Howe) Studying the rules of computation at single neurons across dendritic arbors in the direct and indirect pathways of striatum Dr. Cristina Delgado Sallent (with Profs. Steve Ramirez and Benjamin Scott) Characterizing brain regions and cell populations essential to ketamine’s therapeutic effects Caitlin Lienkaemper (with Prof. Gabriel Ocker) Building a principled, biologically motivated random model for neural activity PREVIOUS FELLOWS Dr. Leah Bakst (with Prof. Joseph McGuire) Awarded both an NSF SPRF fellowship (SMA1809071; 7/1/18-6/30/19) and an NIH F32 fellowship (F32-EY029134) Dr. Tashauna Blankenship (with Prof. Melissa Kibbe and Prof. Chantal Stern) Awarded an NIH NRSA post-doctoral fellowship Dr. Eric Lowet (with Prof. Jerry Chen and Prof. Xue Han) Co-authored a Neuron paper with Prof. Jerry Chen; currently publishing voltage-imaging research with Prof. Xue Han Dr. Joshua Foster (with Prof. Sam Ling) Co-authored paper in Journal of Neuroscience forthcoming Josh said this will be the “Kilachand Fellows” and SB2 Trainees; (internal report will inform?)
ANNUAL REPORT 2023 | 27 PhD student Jillian Ness (left) and Professor Zeba Wunderlich examining fruit fly specimens ANNUAL REPORT 2023 | 27
28 | BOSTON UNIVERSITY BIOLOGICAL DESIGN CENTER ANNUAL REPORT 2022 | 28 Under the microscope at the BDC 28 | BOSTON UNIVERSITY BIOLOGICAL DESIGN CENTER
ANNUAL REPORT 2023 ANNUAL REPORT 2022 | 29 Under the microscope at the BDC 29 | BOSTON UNIVERSITY BIOLOGICAL DESIGN CENTER
30 | BOSTON UNIVERSITY BIOLOGICAL DESIGN CENTER ANNUAL REPORT 2022 | 30 Under the microscope at the BDC 30 | BOSTON UNIVERSITY BIOLOGICAL DESIGN CENTER
ANNUAL REPORT 2023 ANNUAL REPORT 2022 | 31 Under the microscope at the BDC 31 | BOSTON UNIVERSITY BIOLOGICAL DESIGN CENTER
32 | BOSTON UNIVERSITY BIOLOGICAL DESIGN CENTER THE OUTREACH PROGRAM STEM PATHWAYS aims to establish a STEM pipeline by exposing college undergraduates and greater Boston-area high school students to synthetic biology, computational biology, and biotechnology via a range of programming that includes lab-skills training, hackathons, industry internships, and participation in an international synthetic biology design competition. Professor Doug Densmore serves as principal investigator for the $2.3M, three-year Department of Defense STEM grant that supports this program. Hailey Lenn Gordon, who was hired as Director of STEM Pathways in 2022, sat for an interview to share reflections on her first year at the helm. What is the core challenge that STEM Pathways addresses? STEM Pathways aims to overcome the inequity in STEM fields generally and in biotech fields specifically. To pursue professional opportunities in biotech, students need to develop skillsets that are often not featured as part of their basic curriculum. We level the playing field for underserved students, so they can explore an interest in areas like microfluidic technology, cell therapy, or gene editing. Students are increasingly aware of these cool engineering- and science-related things happening around them and they’re wondering how they can get involved. For instance, maybe they hear in the news about CRISPR systems that can be programmed to edit DNA at precise locations, or maybe they get curious about the Impossible Burger they just ate (because that burger was a synthetic biology product). STEM Pathways creates opportunities to get involved in these fields. How does STEM Pathways fit within with the Biological Design Center? The Biological Design Center (BDC) brings together graduate students, postdoctoral fellows, and faculty from multiple disciplines and departments at BU—including biomedical engineering, biology, electrical engineering, computer science, physics, and chemistry—to build a diverse, inclusive, and collaborative community that conducts groundbreaking research in biological design and sets the standards for education and training in synthetic biology and biotechnology. This makes the BDC an outstanding source of experiential learning opportunities for STEM Pathways students. And Professor Douglas Densmore, a BDC faculty member, serves as principal investigator for the grant supporting STEM Pathways. STEM Pathways engages faculty, graduate students, undergraduates, and high school students. How does it all work? The way STEM research laboratories generally work is that graduate students who are pursuing PhD degrees in fields High school students in the STEM Pathways program practice pipetting using dyed water and laminated precision cards. OUTREACH SPOTLIGHTS Building a STEM Research Pipeline BU Scientists Engage High School Students for Hands-on STEM Experience
ANNUAL REPORT 2023 | 33 like biomedical engineering and biology are conducting research as part of their thesis. They work closely with their principal investigators (the faculty) to get mentorship, but they also develop their own research questions. These graduate students, in turn, will often recruit undergraduate students to help them accomplish some of their entry-level lab tasks, so now undergraduate students are getting those basic skills that they may have previously only read about in a paper or a homework assignment. STEM Pathways can facilitate and enhance these research opportunities for undergraduates through our programming. In the summertime, we also invite high school students to come to BU and work in the lab. Integrating high school students essentially creates two levels of mentorship, such that an undergraduate who is paired with a high school student can say “Hey, I just learned this, and now I can teach you.” They receive mentorship from graduate students too, which allows the high school students to observe and understand the educational and professional journey of a scientist—from high school to undergraduate to graduate studies— and how at each level they operate with increasing independence as a researcher. What drew you personally to STEM Pathways? I am an AfricanAmerican woman who was fortunate enough to have family members and mentors in my life who looked like me and were in a STEM field. My aunt works at NASA, my mom’s a nurse, and my uncle is a physician assistant. It wasn’t until I got to college that I realized that wasn’t the norm. I will never forget going to my first computer science class at UC Berkeley. I was probably the only black person in the room, not to mention one of a very small number of women. As I continued to figure out my place in the academic and STEM world, I experienced some imposter syndrome, and I always thought, “I don’t want this to happen to other people,” so I mentored as a volunteer with organizations like Black Girls Code and Tech Girls. Meanwhile, I loved the research I was doing in neural engineering, but I gradually realized that I was even happier helping other people succeed and pushing them to achieve their dreams. Running STEM Pathways helps me stay integrated in the research that’s happening at BU while also letting me mentor and connect other mentors to students who have backgrounds like mine. Give me some examples of the STEM pathways programming. We offer a broad range of programming for high school students. For example, there are wet-lab opportunities, where the students can develop valuable skills that may not be available to them unless they take AP Biology or if their school has a Biotechnology CTE Program. High school students can come to a BDC lab and get one-onone mentorship with both an undergraduate student and a graduate student. They’re assigned a project and a team. They may learn to run a gel, or how to do mini prep, just the beginning steps of wet lab research. We also have smaller opportunities for students who can’t dedicate their whole summer. Our partner, the BioBuilder Educational Foundation, has created a series of fantastic, hands-on modules that we’ve turned into weekend workshops. We also have students who are more interested in computational biology. For them, we do things like hackathons. These aren’t quite like an adult hackathon but more of a tutorial that demonstrates how coding can be used for biology and data and science. A recent one focused on the Python coding language which is super friendly for High school students from the Greater Boston area brainstorm a machine learning solution for a synthetic biology challenge at the STEM Pathways hackathon hosted on BU campus. “Integrating high school students essentially creates two levels of mentorship, such that an undergraduate who is paired with a high school student can say ‘Hey, I just learned this, and now I can teach you.’” - Hailey Lenn Gordon
34 | BOSTON UNIVERSITY BIOLOGICAL DESIGN CENTER students with no prior experience. We demonstrate how a basic coding package would work if you were trying to edit a gene. The coding isn’t as complicated as they use in the real world, but it lays the foundations and gets students thinking about how valuable it is if they can learn a little bit of coding. Besides wet-lab and computational opportunities, we also offer a free virtual course in synthetic biology— three introductory lectures where we’re giving examples about what synthetic biology is, how it’s used in the real world, or where you may have seen it before. Afterward participants can direct questions to graduate students and PIs. We try to use the virtual courses as a gateway that draws students to the more hands-on opportunities like wet labs and hackathons. And we run mini-Jamborees, which are free, interactive days of learning and fun to increase awareness of synthetic biology and biotechnology. STEM Pathways also supports students in a worldwide synthetic biology project competition. Can you say more about that? Yes! The International Genetically Engineered Machine (or iGEM) Competition creates opportunities for multidisciplinary student teams to work together to design, build, test, and measure a system using interchangeable biological parts and standard molecular biology techniques. STEM Pathways is responsible for coordinating and supporting Boston University’s iGEM team which can comprise a collaboration of undergraduate students, high school students, and graduate student mentors from any fields who are interested in trying to tackle some synthetic biology problem. The annual competition takes place in Paris, France, and that’s where we go every year to present our ideas—a good perk of being on the iGEM team! The 2022 iGEM Team received a gold medal and a nomination for the Best Environment Project. The competition is a great collaboration opportunity that can synthesize a broad range of students’ majors, ideas, and interests—for instance, you might have a student who’s interested in robotics coming up with cool hardware they want to test on a biological process. Have you observed changes in participants’ attitudes toward STEM as a potential career path? You can see their body language change over the course of the semester, their willingness to stand up and speak about what they’re doing. At the welcome kickoff meeting, when I tell them that they’re going to be making a final presentation at the end of the semester, most of them look at me like a deer in headlights. Undergraduates often have this sense at the beginning that they are just a worker bee, someone behind the scenes with no ownership of the research happening. But by the time they are preparing their final poster presentation, I can see how much their confidence and enthusiasm has grown. Another marker of their confidence is in the lab skills they’ve developed. For instance, there’s a basic biotech procedure known as “running a gel,” and it’s the first task students are assigned in the lab. In the beginning of the semester I hear, “It did not work today. It didn’t work yesterday. It’s probably never going to work.” And by the end of the semester they’re saying, “Oh, we do those in our sleep now.” Are the people providing instruction and mentorship volunteers? Apart from myself, all STEM Pathways mentors are volunteers. My strong suits are neural engineering or computation, but for any area outside my expertise, like gene editing, I must definitely lean on grad students and PIs with experience in those areas and ask if they’d be willing to help me develop lecture modules and coding challenges. Even my undergraduate students— who often experience both sides of mentorship in STEM STEM Pathways Director Hailey Gordon “You can see their body language change over the course of the semester, their willingness to stand up and speak about what they’re doing..’” - Hailey Lenn Gordon
ANNUAL REPORT 2023 | 35 Pathways—volunteer at these things as Q&A discussants or teaching assistants. What would you want to say to scientists you haven’t recruited yet about getting involved? I think it’s a lower lift than most busy scientists are expecting. Do you have an hour to give a research talk or a Q&A session? All I need you to do is tell them about your research, and I’ll figure out the logistics. I can reserve the room, bring the students, bring the snacks. You just show up and provide your knowledge. Does your grant have an outreach component? I’m happy to help you come up with a plan for broadening participation that complements your research and integrates well with what STEM Pathways is already doing. Maybe that means tailoring our hackathon curriculum to better reflect what you’re doing in your lab. Maybe it’s conducting a lab experiment for students that represents a base level of the work happening in your lab. It’s all about integrating the grant’s research objectives with a curriculum applicable to younger students that helps broaden the overall impact. I’ve helped lots of PIs write those types of things. Are there opportunities for non-BDC researchers at Boston University to get involved with STEM Pathways? The STEM Pathways grant focuses on the fields of synthetic biology and computational biology, but there are so many ways the other STEM fields can connect to those two. For instance, we’ve been able to talk about robotics through automation and automating different synthetic biology processes. We’ve been able to talk about general biology and computer engineering via the computational tools or by talking about biological circuits. I can be very creative about finding ways your research connects to synthetic biology. * * * This interview, conducted and edited by Jim Cooney, originally appeared in the Rajen Kilachand Center for Integrated Life Sciences & Engineering blog on October 12, 2023. To read the original article visit: tinyurl.com/46ck8vay STEM Pathways Students Speak Out Brooklynn Marcelin (high school student) What did you work on this week? “I worked mainly on finishing my projects and on our construct because there was a mutation we had to fix in the gene. I also got to shadow my mentor while he worked in the cell culture room which I thought was nice.” What was your favorite part of this week? “I really like talking to my mentor and partner when we’re working in the lab, hearing how he got to where he is and how.” Marko Radulovic (undergraduate) What did you work on this week? “I did practice microinjections at the 2-cell stage with a dye and started my first attempt at our lab’s Alcian blue stain protocol.” What major goal do you want to accomplish by end of summer? “I want to finish the manuscript [I’m working on] for my first co-authorship.”
36 | BOSTON UNIVERSITY BIOLOGICAL DESIGN CENTER THE ANNUAL International Genetically Engineered Machine (iGEM) competition is a momentous opportunity for engineering students with a passion for synthetic biology to gain valuable hands-on experience and make their big ideas into solid reality. Boston University has sponsored a team for the competition for many years now, with the dedicated support of Professor Douglas Densmore and STEM Pathways. In 2022, the BU Hardware team’s hard work paid off with multiple honors: a gold medal and a nomination for the Best Environment Project. Even more importantly, they fulfilled the mission they began with: to create a novel technology with the potential to make a meaningful impact on society. The 2022 BU team, Aquamatic Technologies (AT), designed a hardware system intended to improve and streamline the process of testing water samples for contaminants using biosensors (biological systems, such as bacterial colonies, which can be “used for detecting foreign materials by converting signals to measurable responses,” according to the AT website). In designing their product, the team placed particular emphasis on user-friendliness, modularity, portability, broad compatibility with a variety of existing systems and installations, and customization. As their slogan suggests, their target was the capacity to do no less than “[test] the world’s water, one drop at a time;” they have built a prototype for a technology that they envision deploying worldwide. That technology, dubbed the AM1, is a self-contained water-testing system made up of components which can be rearranged and customized for a variety of purposes; the housing keeps the electronic and fluid components safely separate, but integrated, and can be disassembled easily for transit or cleaning. It utilizes microfluidic technology–cheaply and easily produced plastic chips which use very small amounts of liquid for testing–for a fully automated testing process which combines a water sample with a chosen biosensor and measures the resulting reaction. The water sample can either be added from the existing environment which the user wishes to test, or it can be created based on custom parameters (such as pH and salinity). This allows significant flexibility if a user does not have direct access to their water source or wants to test a hypothetical set of variables. The results, once ready, can provide valuable information about the presence of chemical contaminants – and because the testing process is fully automated, it’s safer and faster than traditional testing, where human technicians would be handling the materials directly. The AT also created the AM1 with biosensor testing in mind. In addition to the critical importance of teamwork, the iGem competition emphasizes the value of broad communication and collaboration. AT took this to heart, meeting with bioengineers, workers at Boston’s own Deer Island Water Treatment Plant, members of the 2018 BU iGEM team, and the 2022 MIT iGEM team, at various points throughout their process. Insights from researchers and water treatment workers helped them to pinpoint challenges in current practice which their product could most usefully address; studying past iGEM projects gave them a sense of the level of documentation One Drop at a Time BU iGem Team Brings Home Gold Medal The BU team that competed in the 2022 iGEM competition consisted of (top row, left to right) Alex Barutis (BME’23), , Aya Kassem (ECE’24), Zakir Kadwa (ME’24), Julia Nowak (BME’25), and Stephen Sweet (ECE/BME’23)
ANNUAL REPORT 2023 | 37 and communication they could create to make their ideas reproducible and allow others to build on them; and their meetings with the MIT team gave both groups the opportunity to brainstorm and exchange feedback with similarly motivated peers; all of which helped to transform and greatly improve their final product. The BU team also engaged in a number of outreach events with K-12 students, giving back to their community; possibly even to members of future iGEM teams. Ultimately, the Aquamatic team’s biggest contribution to BU’s iGEM legacy may be their system’s modular design, which sets them apart from past projects focused on biosensors, aquatic environments, and/or water testing. They documented every step of the build process, which they completed at BU’s own EPIC facility, and have made their code publicly available, very much in the tradition of their PI’s dedication to the democratization of synbio research. In October, the team traveled to Paris to attend the competition’s culminating event, the iGEM Jamboree; sharing their work not only with judges and experts, but with members of 355 other student teams from around the globe. The AM1 garnered them a gold medal in recognition of their excellence in fulfilling (and in some cases surpassing) the competition criteria, as well as a nomination for the Best Project in the year’s most competitive track, Environment. On the heels of that triumph, STEM Pathways and its Program Coordinator, Hailey Lenn Gordon, are gearing up for iGEM 2023 – the competition’s 20th year. Current BU undergrads who are interested in following in Aquamatic Technologies’ footsteps can apply to join the 2023 team using this form. They’ll be contributing to what has become an exciting BU tradition, in the vital spirit of convergent engineering research. And what of the AM1? According to Gordon, it is destined for laboratory use right here in BU labs as a simulation device to assist with testing novel biosensors; continuing that iGEM tradition of collaboration and “paying it forward” between researchers, present and future. * * * This article, authored by Allison Kleber, originally appeared in the BU Engineering blog on February 16, 2023. To read the original article visit: tinyurl.com/mr2ua2d7 The AM1 prototype.
38 | BOSTON UNIVERSITY BIOLOGICAL DESIGN CENTER ACHIEVEMENTS & AWARDS CENTER FACULTY EARNED VARIOUS AWARDS and achievements over the course of the past fiscal year. These include: Christopher Chen • Fellow, The National Academy of Inventors • promoted to Core Faculty Member, The Wyss Institute for Biological Inspired Systems at Harvard University Brian Cleary • Awarded a Kilachand Fund award (with Michael Economo and Jerry Chen) for $500,000 Mary Dunlop: Fellow, American Institute for Medical and Biological Engineering Jeroen Eyckmans • Dean’s Catalyst Award (with Emma Lejeune) for $100,000 Juan Fuxman Bass: promoted to Associate Professor, Boston University Alexander Green: promoted to Associate Professor, Boston University Ahmad (Mo) Khalil • promoted to Professor, Boston University • Outstanding Professor of the Year, College of Engineering, Boston University • Award for Teaching Excellence, Department of Biomedical Engineering, Boston University Mo Khalil, W. M. Keck Foundation Medical Research Award John Ngo • promoted to Associate Professor, Boston University Arturo Vegas: Novartis Global Scholars Program Finalist Arturo Vegas • Juvenile Diabetes Research Foundation (JDRF) Innovator Award Zeba Wunderlich: promoted to Associate Professor, Boston University Rabia Yazicigil • Senior Member, Institute of Electrical and Electronics Engineers (IEEE) Caption
ANNUAL REPORT 2023 | 39 SELECTED EVENTS THE CENTER HOSTED A SYMPOSIUM and a number of seminars at Boston University featuring both BU speakers and external speakers as well as candidates for faculty positions in relevant departments. These events, promoted internally via departmental email lists and to the public via Twitter, attracted audiences of 60-500 researchers from a wide range of fields including: the CAS departments of Psychological and Brain Sciences, Biology, Physics, and Mathematics and Statistics; the Sargent School departments of Health Sciences and Speech, Language and Hearing Sciences; the School of Medicine departments of Anatomy and Neurobiology and Pharmacology and Experimental Therapeutics; and the School of Engineering departments of Biomedical Engineering and Electrical and Computer Engineering. FALL 2021 September 8th Early Career Workshop • For junior faculty and post-doctoral fellows affiliated with the CSN; information on grant funding from the BU Federal Relations Office and Foundation Relations Office • Organized with Vice President of Federal Relations Jennifer Grodsky September 22nd Prof. Benjamin Scott • Boston University, Department of Psychological and Brain Sciences • Title: Neural mechanisms for inference and decision making • Hosted by Prof. Michael Hasselmo October 5th – 6th SYMPOSIUM: Advances in Systems and Computational Neuroscience • Nancy Kopell, Boston University - “How does deep brain stimulation work for Parkinson’s disease?” • Brent Doiron, University of Chicago - “Cellular mechanisms for quenching neuronal variability” • Sam Gershman, Harvard University - “Dopamine prediction errors are dead, long live dopamine prediction errors!” • Xue Han, Boston University - “Calcium and voltage imaging analysis of neural network across spatiotemporal scales during behavior” • Tatiana Engel, CSHL - “Latent circuits in recurrent neural networks” • Jennifer Luebke, Boston University - “Diversity and selective vulnerability of cortical pyramidal neurons” • Kanaka Rajan, Mount Sinai - “How brain circuits Professor Joseph Larkin provides highlights from his lab during Kilachand Day celebration.
40 | BOSTON UNIVERSITY BIOLOGICAL DESIGN CENTER function in health and disease: Understanding brainwide current flow” • Stefano Fusi, Columbia University - “The role of hippocampus in memory compression” • Ila Fiete, MIT - “Place cells: capacity, volatility, and predetermined scaffolds” • Demba Ba, Harvard University - “Sparse coding, artificial neural networks, and the brain: Toward ‘Substantive Intelligence’” • Jerry Chen, Boston University - “CRACKing neural circuits underlying behavior” October 27th Prof. Michael Yartsev • University of California, Berkeley, Department of Bioengineering • Title: Neural mechanisms of complex spatial, social and acoustic behaviors in bat • Hosted by Prof. Jerry Chen November 3rd Prof. Scott Linderman • Stanford University, Department of Statistics • Title: Discovering structure in neural and behavioral data • Hosted by Prof. Benjamin Scott SPRING 2022 February 9th Prof. Keri Martinowich • Johns Hopkins University, Department of Neuroscience • Title: Cell-type and spatially resolved molecular signatures in human brain disorders • VIRTUAL event hosted by Dr. Madelyn Ray February 23rd Prof. Gordon Fishell • Harvard University, HMS Neurobiology • Title: The intimate dependence and remarkable precision of cortical interneuron-pyramidal cell connectivity • IN-PERSON and VIRTUAL event hosted by Profs. Shelley Russek and Heidi Meyer March 30th Prof. Meyer Jackson • University of Wisconsin-Madison, Department of Neuroscience • Title: Revealing neural circuit mechanisms with voltage imaging • IN-PERSON and VIRTUAL event hosted by Prof. Xue Han Professor John Ngo presents findings from his lab in the Howard Eichenbaum Colloquium Room Scott Behie, Ph.D., scientic editor for Cell, provides insight into the journal’s editorial process
ANNUAL REPORT 2023 | 41 April 6th Prof. Alain Destexhe • CNRS and Paris-Saclay University, France • Title: Multiscale modeling of brain states, from spiking networks to the whole brain • VIRTUAL event hosted by Prof. Emily Stephen April 13th Prof. Andreas Nieder • University of Tübingen, Germany, Institute of Neurobiology • Title: Neuronal code for numbers in humans, monkeys and crows • VIRTUAL event hosted by Prof. Benjamin Scott April 27th CSN Post-Doc and Faculty Social • An opportunity for CSN postdoctoral researchers and faculty members to engage beyond the lab May 4th Prof. Liset M. de la Prida • Instituto Cajal – CSIC, Spain • Title: Dissecting subcircuits underlying hippocampal function • VIRTUAL event hosted by Dr. Andy Alexander May 18th Dr. Alex Mathis • DeepLabCut, EPFL • Title: Measuring and modeling behavior with deep learning • IN-PERSON event hosted by Prof. Steve Ramirez June 28th Tutorial and Joint Social • Opportunity for CSN-affiliated graduate students, postdoctoral researchers, and faculty to learn about novel techniques and build community. Jun Shen and Joshua Finkelstein enjoy a catered event in the courtyard.
42 | BOSTON UNIVERSITY BIOLOGICAL DESIGN CENTER HOW TO ENGAGE WITH US Quiamus eos con nat latur renecus dolorae veristium velectem hitatem suscias sanditio. Et volupist lam, sed que velitis nisqui dolorest, quate corro cuptaesti ne sim nosaper uptatibus, quisiminciet optaquat fugia ex et ea nostes et quost, quunt liqui ata quunt odia cuptate necesentio eictis venis sitat quaerem ati rempos vellacc aeptae. Agnam, te odi non rempe verate explant occumet volupta pe molo veritiis entio conemod excesto mod quis everibus eos min cusciendis saperaturit quation re culparit STAY CONNECTED TO THE CENTER 610 Commonwealth Avenue Boston, MA 02215 www.bu.edu/bdc https://twitter.com/BioDesignCenter Back cover photo: Caption JOSH: You had some thoughts on this but I forgot what we discussed we would include here.
610 COMMONWEALTH AVENUE BOSTON, MA 02215 WWW.BU.EDU/BDC Boston University Biological Design Center JOSH: Will the BDC Symposium provide an opportunity for a whole group (or near whole group) photo?