Illuminating the Unseen: Former Penn iGEM Team Publishes Award-Winning Optogenetic Device

Diagram of the optoPlateReader, a high-throughput, feedback-enabled optogenetics and spectroscopy device initially developed by Penn 2021 iGEM team.

For bioengineers today, light does more than illuminate microscopes. Stimulating cells with light waves, a field known as optogenetics, has opened new doors to understanding the molecular activity within cells, with potential applications in drug discovery and more.

Thanks to recent advances in optogenetic technology, much of which is cheap and open-source, more researchers than ever before can construct arrays capable of running multiple experiments at once, using different wavelengths of light. Computing languages like Python allow researchers to manipulate light sources and precisely control what happens in the many “wells” containing cells in a typical optogenetic experiment.

However, researchers have struggled to simultaneously gather data on all these experiments in real time. Collecting data manually comes with multiple disadvantages: transferring cells to a microscope may expose them to other, non-experimental sources of light. The time it takes to collect the data also makes it difficult to adjust metabolic conditions quickly and precisely in sample cells.

Now, a team of Penn Engineers has published a paper in Communications Biology, an open access journal in the Nature portfolio, outlining the first low-cost solution to this problem. The paper describes the development of optoPlateReader (or oPR), an open-source device that addresses the need for instrumentation to monitor optogenetic experiments in real time. The oPR could make possible features such as automated reading, writing and feedback in microwell plates for optogenetic experiments.

Left to right: Will Benman, Gloria Lee, Saachi Datta, Juliette Hooper, Grace Qian, David Gonzalez-Martinez, and Lukasz Bugaj (with Max).

The paper follows up on the award-winning work of six University of Pennsylvania alumni — Saachi Datta, M.D. Candidate at Stanford School of Medicine; Juliette Hooper, Programmer Analyst in Penn’s Perelman School of Medicine; Gabrielle Leavitt, M.D. Candidate at Temple University; Gloria Lee, graduate student at Oxford University; Grace Qian, Drug Excipient and Residual Analysis Research Co-op at GSK; and Lana Salloum, M.D. Candidate at Albert Einstein College of Medicine — who claimed multiple prizes at the 2021 International Genetically Engineered Machine Competition (iGEM) as Penn undergraduates.

The International Genetically Engineered Machine Competition (or iGEM) is the largest synthetic biology community and the premiere synthetic biology competition for both university and high school students from around the world. Hundreds of interdisciplinary teams of students compete annually, combining molecular biology techniques and engineering concepts to create novel biological systems and compete for prizes and awards through oral presentations and poster sessions.

The optoPlateReader was initially developed by Penn’s 2021 iGEM team, combining a light-stimulation device with a plate reader. At the iGEM competition, the invention took home Best Foundational Advance (best in track), Best Hardware (best from all undergraduate teams), and Best Presentation (best from all undergraduate teams), as well as a Gold Medal Distinction and inclusion in the Top 10 Overall and Top 10 Websites lists. (Read more about the 2021 iGEM team on the BE Blog.)

The original iGEM project focused on the design, construction, and testing of the hardware and software that make up the oPR, the focus of the new paper. After iGEM concluded, the team showed that the oPR could be used with real biological samples, such as cultures of bacteria. This work demonstrated that the oPR could be applied to real research questions, a necessary precursor to publication, and that the device could simultaneously monitor and manipulate living samples. 

The main application for the oPR is in metabolic production (such as the creation of pharmaceuticals and bio-fuels). The oPR is able to issue commands to cells via light but can also take live readings about their current state. In the oPR, certain colors of light cause cells to carry out different tasks, and optical measurements give information on growth rates and protein production rates.

In this way, the new device is able to support production processes that can adapt in real time to what cells need, altering their behavior to maximize yield. For example, if an experiment produces a product that is toxic to cells, the oPR could instruct those cells to “turn on” only when the population of cells is dense and “turn off” when the concentration of that product becomes toxic and the cellular population needs to recover. This ability to pivot in real time could assist industries that rely on bioproduction.

The main challenges in developing this device were in incorporating the many light emitting diodes (LEDs) and sensors into a tiny space, as well as insulating the sensors from the nearby LEDs to ensure that the measured light came from the sample and not from the instrument itself. The team also had to create software that could coordinate the function of nearly 100 different sets of LEDs and sensors. Going forward, the team hopes to spread the word about the open-source oPR to other researchers studying metabolic production to enable more efficient research.

Lukasz Bugaj, Assistant Professor in Bioengineering and senior author of the paper, served as the team’s mentor along with Brian Chow, formerly an Associate Professor in Bioengineering and a founding member of the iGEM program at MIT, and Jose Avalos, Associate Professor of Chemical and Biological Engineering at Princeton University.

Key to the project’s development was the guidance of Bioengineering graduate students Will Benman, David Gonzalez Martinez, and Gabrielle Ho, as well as that of Saurabh Malani, a graduate student at Princeton University.

Much of the original work was conducted in Penn Bioengineering’s Stephenson Foundation Educational Laboratory & Bio-MakerSpace, with important contributions made by Michael Patterson, Director of Educational Laboratories in Bioengineering, and Sevile Mannickarottu, Director of Technological Innovation and Entrepreneurship in Penn Engineering’s Entrepreneurship Program.

Read “High-throughput feedback-enabled optogenetic stimulation and spectroscopy in microwell plates” in Communications Biology.

This project was supported by the Department of Bioengineering, the School of Engineering and Applied Science, and the Office of the Vice Provost for Research (OVPR), and by funding from the National Institute of Health (NIH), the National Science Foundation (NSF), and the Department of Energy (DOE).

The iGEM program was created at the Massachusetts Institute of Technology in 2003. Read stories in the BE Blog featuring recent Penn iGEM teams here.

2023 PIP-Winning Team Sonura: Where Are They Now?

Members of Team Sonura: Tifara Boyce, Gabriela Cano, Gabriella Daltoso, Sophie Ishiwari, & Caroline Magro (credit: Penn BE Labs)

In April 2023, three President’s Prize-winning teams were selected from an application pool of 76 to develop post-graduation projects that make a positive, lasting difference in the world. Each project received $100,000 and a $50,000 living stipend per team member.

The winning projects include Sonura, the winner of the President’s Innovation Prize (PIP), who are working to improve infant development by reducing harsh noise exposure in neonatal intensive care units. To accomplish this, they’ve developed a noise-shielding beanie that can also relay audio messages from parents.

Sonura, a bioengineering quintet, developed a beanie that shields newborns from the harsh noise environments present in neonatal intensive care units (NICUs)—a known threat to infant wellbeing—and also supports cognitive development by relaying audio messages from their parents.

Since graduating from the School of Engineering and Applied Science, the team of Tifara Boyce, Gabriela Cano, Gabriella Daltoso, Sophie Ishiwari, and Caroline Magro, has collaborated with more than 50 NICU teams nationwide. They have been helped by the Intensive Care Nursery (ICN) at the Hospital of the University of Pennsylvania (HUP), which shares Sonura’s goal of reducing NICU noise. “Infant development is at the center of all activities within the HUP ICN,” note Daltoso and Ishiwari. “Even at the most granular level, like how each trash can has a sign urging you to shut it quietly, commitment to care is evident, a core tenet we strive to embody as we continue to grow.” 

An initial challenge for the team was the inability to access the NICU, crucial for understanding how the beanie integrates with existing workflows. Collaboration with the HUP clinical team was key, as feedback from a range of NICU professionals has helped them refine their prototype.

In the past year, the team has participated in the University of Toronto’s Creative Destruction Lab and the Venture Initiation Program at Penn’s Venture Lab, and received funding from the Pennsylvania Pediatric Device Consortium. “These experiences have greatly expanded our perspective,” Cano says.

With regular communication with mentors from Penn Engineering and physicians from HUP, Children’s Hospital of Philadelphia, and other institutes, Sonura is looking ahead as they approach the milestone of completing the FDA’s regulatory clearance process within the year. They will begin piloting their beanie with the backing of NICU teams, further contributing to neonatal care.

Read the full story and watch a video about Sonura’s progress in Penn Today.

Read more stories featuring Sonura in the BE Blog.

Estelle Sunghee Park Appointed Assistant Professor at Purdue University

Estelle Park, Ph.D.

Penn Bioengineering is proud to congratulate Sunghee Estelle Park, Ph.D. on her appointment as Assistant Professor in the Weldon School of Biomedical Engineering at Purdue University. Park earned her Ph.D. at Penn Bioengineering, graduating in July 2023. She conducted doctoral research in the BIOLines Lab of Dan Huh, Associate Professor in Bioengineering. Her appointment at Purdue will begin January 2024.

During her Ph.D. research, Park forged a unique path that combined principles in developmental biology, stem cell biology, organoids, and organ-on-a-chip technology to develop innovative in vitro models that can faithfully replicate the pathophysiology of various human diseases. Using a microengineered model of the human retina, she discovered previously unknown roles of the MAPK, IL-17, PI3K-AKT, and TGF-β signaling pathways in the pathogenesis of age-related macular degeneration (AMD), presenting novel therapeutic targets that could be further investigated for the development of AMD treatments. More recently, she tackled a significant challenge in the organoid field, the limited tissue growth and maturity in conventional organoid cultures, by designing microengineered systems that enabled organoids to grow with unprecedented levels of maturity and human-relevance. By integrating these platforms with bioinformatics and computational analyses, she identified novel disease-specific biomarkers of inflammatory bowel disease (IBD) and intestinal fibrosis, including previously unknown link between the presence of lncRNA and the development of IBD.

“The unique interdisciplinary expertise I gained from these projects has shaped me into a scholar with a strong collaborative ethos, a quality I hold in high esteem as we work towards advancing our knowledge and management of health and disease,” says Park.

Her vision as an independent researcher is to become a leading faculty who makes impactful contributions to our fundamental understanding of the factors influencing the structural and functional changes of human organs in health and disease. To achieve this, she plans to lead a stem cell bioengineering laboratory with a primary focus on tissue engineering and regenerative medicine. This will involve developing human organoids-on-a-chip systems and establishing next-generation biomedical devices and therapies tailored for regenerative and personalized medicine.

“I am grateful to all my Ph.D. mentors and lab mates at the BIOLines lab and especially my advisor Dr. Dan Huh, for his exceptional guidance, unwavering support, and invaluable mentorship throughout my Ph.D. journey,” says Park. “Dan’s expertise, dedication, and commitment to excellence have been instrumental in shaping both my research and professional development, while also training me to become an independent scientist and mentor.”

Congratulations to Dr. Park from everyone at Penn Bioengineering!

“QR Code for Cancer Cells” – Uncovering Why Some Cells Become Resistant to Anti-Cancer Therapies

by Win Reynolds

QR codeA research team led by engineers at the University of Pennsylvania and Northwestern University scientists has created a new synthetic biology approach, or a “QR code for cancer cells,” to follow tumor cells over time, finding there are meaningful differences in why a cancer cell dies or survives in response to anti-cancer therapies.

Remarkably, what fate cancer cells choose after months of therapy is “entirely predictable” based on seemingly small, yet important, differences that appear even before treatment begins. The researchers also discovered the reason is not genetics, contrary to beliefs held in the field.

The findings were recently published in Nature.

The study outlined the team’s new technology platform that developed a QR code for each of the millions of cells for scientists to find and use later — much like tagging swans in a pond. The QR code directs researchers to a genome-wide molecular makeup of these cells and provides information about how they’ve reacted to cancer treatment.

“We think this work stands to really change how we think about therapy resistance,” said Arjun Raj, co-senior author and Professor in Bioengineering in the School of Engineering and Applied Science at the University of Pennsylvania. “Rather than drug-resistant cells coming in just one flavor, we show that even in highly controlled conditions, different ‘flavors’ can emerge, raising the possibility that each of these flavors may need to be treated individually.”

In the study, the lab and collaborators sought to apply synthetic biology tools to answer a key question in cancer research: What makes certain tumors come back a few months or years after therapy? In other words, could the lab understand what causes some rare cells to develop therapeutic resistance to a drug?

“There are many ways cells become different from each other,” said Yogesh Goyal, the co-senior author at Northwestern University. “Our lab asks, how do individual cells make decisions? Understanding this in the context of cancer is all the more exciting because there’s a clinically relevant dichotomy: A cell dies or becomes resistant when faced with therapies.”

Using the interdisciplinary team, the scientists put the before-and-after cloned cells through a whole genome sequencing pipeline to compare the populations and found no systematic underlying genetic mutations to investigate the hypothesis. Raj and Goyal  helped develop the QR code framework, FateMap, that could identify each unique cell that seemed to develop resistance to drug therapy. “Fate” refers to whether a cell dies or survives (and if so, how), and the scientists “map” the cells across their lifespan, prior to and following anti-cancer therapy. FateMap is the result of work from several research institutions, and it applies an amalgamation of concepts spanning several disciplines, including synthetic biology, genome engineering, bioinformatics, machine learning and thermodynamics.

“Some are different by chance — just as not all leaves on a tree look the same — but we wanted to determine if that matters,” Goyal said. “The cell biology field has a hard time defining if differences have meaning.”

Read the full story in Penn Engineering Today.

Engheta, Margulies Elected to the American Academy of Arts & Sciences

Two faculty affiliated with the Department of Bioengineering at the University of Pennsylvania have been elected to the American Academy of Arts & Sciences. They join nearly 270 new members honored in 2023, recognized for their excellence, innovation, leadership, and broad array of accomplishments.

Nader Engheta
Nader Engheta, the H. Nedwill Ramsey Professor.

Nader Engheta is the H. Nedwill Ramsey Professor, with affiliations in the departments of Electrical and Systems Engineering (primary appointment), Bioengineering (secondary appointment) and Materials Science and Engineering (secondary appointment) in the School of Engineering and Applied Science; and Physics and Astronomy (secondary appointment) in the School of Arts & Sciences. His current research activities span a broad range of areas including optics, photonics, metamaterials, electrodynamics, microwaves, nano-optics, graphene photonics, imaging and sensing inspired by eyes of animal species, microwave and optical antennas, and physics and engineering of fields and waves. He has received numerous awards for his research, including the 2023 Benjamin Franklin Medal in Electrical Engineering, the 2020 Isaac Newton Medal and Prize from the Institute of Physics (U.K.), the 2020 Max Born Award from OPTICA (formerly OSA), induction to the Canadian Academy of Engineering as an International Fellow (2019), U.S. National Academy of Inventors (2015), and the Ellis Island Medal of Honor from the Ellis Island Honors Society (2019). He joins four other Penn faculty elected to the Academy this year.

Read the announcement and the full list of Penn electees in Penn Today.

Susan Margulies, Ph.D. (Photo: Jack Kearse)

Susan Margulies, Professor in the Wallace H. Coulter Department of Biomedical Engineering in the College of Engineering at Georgia Tech, was also elected. Margulies is both Professor Emeritus in Penn Bioengineering and an alumna of the program, having earned her Ph.D. with the department in 1987. Margulies is an expert in pediatric traumatic brain injury and lung injury. She previously served as Chair of Biomedical Engineering at Georgia Tech/Emory University and in 2021 became the first biomedical engineer selected to lead the National Science Foundation’s (NSF) Directorate of Engineering.

Read the announcement of Margulies’ elected to the Academy at Georgia Tech.

Penn Bioengineering Alumnus Michael Magaraci Featured with New Haven Recycling Startup

Recycling bin full of plastic water bottles.
Credit: sdominick/Getty Images.

Michael Magaraci, Research Scientist at Protein Evolution and alumnus of Penn Bioengineering, featured in CT Insider for the New Haven, CT startup’s quest to replace the global recycling system. The company, founded in 2021, is working on methods to eventually recycle polyester fabrics, rugs, and other materials that end up in landfills. Magaraci, who serves as director of platform engineering, earned a bachelor’s degree in Bioengineering and Economics in the Jerome Fisher Program in Management & Technology from Penn Engineering and the Wharton School of Business in 2013. He stayed with Penn Bioengineering for his doctoral research, completed in 2021. During his time at Penn, he worked as a Teaching Assistant and Laboratory Technician, advised Penn iGEM Teams, and served with Engineers Without Borders.

Read “Meet the New Haven startup that wants to digest your plastic” in CT Insider.

Penn Bioengineering Alumnus Joshua Doloff Seeks a Pain-free Treatment for Diabetes

Person taking a finger stick blood test.
Credit: Darryl Leja, NHGRI Flickr

Joshua C. Doloff, Assistant Professor of Biomedical Engineering and Materials Science & Engineering at Johns Hopkins University, featured in The Jewish News Syndicate for his work on “Hope,” a new technology which offers pain- and injection-free treatment to people with Type 1 or “juvenile” diabetes. Doloff is an alumnus of Penn Bioengineering, Class of 2004:

“Doloff received his bachelor’s degree from the University of Pennsylvania and his graduate degrees from Boston University. In addition to his post in Johns Hopkins’ Department of Biomedical Engineering, he is a member of the Translational Tissue Engineering Center at Johns Hopkins University School of Medicine. His lab is interested in systems biology with an emphasis on engineering improved therapies in the fields of cancer, autoimmunity, transplantation medicine, including Type 1 diabetes and ophthalmology.”

Read “Technion researchers offer ‘Hope’ for treating diabetes, minus the painful jabs” in the Jewish News Syndicate.

2022 PIP/PEP Prize Winners: Where are they now?

by Brandon Baker

William Danon and Luka Yancopoulos pose in front of College Hall in April 2022. They are co-founders of Grapevine and the winners of the 2022 President’s Innovation Prize. (Photo: Eric Sucar)

In April 2022, three President’s Prize-winning teams were selected from an applicant pool of 71 people to develop projects that promote engagement and innovation. Each project received $100,000, as well as a $50,000 living stipend per team member.

The President’s Innovation Prize and President’s Engagement Prize winners included Grapevine, which aims to better connect buyers and suppliers to stabilize the medical supply chain market; IF Ventures, with its mission to scale impact by supporting college students with early-stage startup ideas that have measurable social and environmental impact; and Cosmic Writers, which organizes writing workshops to cultivate K-12 students to be better writers and communicators — and, therefore, better citizens.

“In less than a year, these three PIP and PEP prize-winning teams have already proven their commitment to making a difference in the world,” says President Liz Magill. “Their projects are ambitious and inspiring, and I am proud the University has been able to provide financial and networking support for these determined changemakers.”

Grapevine, 2022 President’s Innovation Prize Winners

After graduating in May 2022, Luka Yancopoulos, an Environmental Studies major and a Bioengineering major in the School of Engineering and Applied Science and William Danon, a History major, relocated to an office space in Westchester, New York, and got to work on a research and validation process — first, by spending a day at a Penn Medicine facility, Lancaster General Health, then by committing hundreds of hours to interviewing distributor and procurement teams alike, along with potential client companies. The mission, as any researcher knows, was to understand key pain points. They also onboarded veterans in logistics, technology, and payment security and processing while devising an organizational structure in which Yancopoulous leads on technology and design solutions while Danon interfaces with customers to know what needs remain unmet.

Grapevine soft launched in fall 2022 and, they say, has interfaced with 30 companies through its digital platform to facilitate sales among 40 suppliers, amounting to more than $20,000 in transactions. The appeal of the platform, they say, remains the concept of the “digital supply chain network,” which Yancopoulos says partners can use to connect with resellers, hospitals, distributors, and others to reduce the risk of supply chain disruption that is not just a product of the pandemic, he adds, but “forever ongoing.”

“It’s driven by the principle that together we’re stronger, and I mean that in every aspect of my life,” he says. “That people are stronger, and with Grapevine we work to [bolster] supply chains and increase the accessibility of health care products — together.”

Since winning the President’s Innovation Prize, they’ve focused on working with small- to medium-sized businesses — whether local clinics or high-quality, specialized resellers — that struggle to compete with or pay for traditional, large-scale distributors that are better-resourced or too expensive. It’s allowed them to also find new users, like health care-adjacent businesses including funeral homes and tattoo parlors.

Their current tagline: “Grow with us,” Danon says.

Watch a video overview of Grapevine’s progress since receiving the PIP prize and read more about the other PIP/PEP prize winners at Penn Today.

Read more stories featuring Grapevine.

Announcing the Madison ‘Maddie’ Magee Award for Undergraduate Excellence

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Maddie MageePenn Engineering is proud to announce the establishment of the Madison “Maddie” Magee Award for Undergraduate Excellence, named in honor of the memory of Madison “Maddie” N. Magee, who graduated with both a bachelor’s degree in Mechanical Engineering and Applied Mechanics (MEAM) and a master’s degree in Bioengineering (BE) in 2021. Following her time at Penn, Maddie joined the Integrative Baseball Performance department of the Philadelphia Phillies, where she collaborated with a group in developing the next generation of baseball players by analyzing biomechanics data.

To establish this award, 130 donors, including the Philadelphia Phillies, came together in 2022 to raise over $50,000, meaning that undergraduate students will be able to receive this award in perpetuity. Recipients will be Penn Engineering seniors who “exemplify the energy, enthusiasm, and excellence that was Maddie.”

“Maddie was full of life and promise and brought unmatched passion and spirit to everything she did,” says Kevin T. Turner, Professor and Chair of MEAM. “It was impossible to not see the impact that she was having on our Department and the School.” Magee excelled as a student at Penn, working as a Teaching Assistant at both Penn and Drexel and providing countless hours of tutoring to fellow students.

It is with deep gratitude for Maddie’s profound and lasting impact on many students, faculty and staff that this award is established.

Maddie passed away while hiking the Pacific Crest Trail on May 28, 2022.

This story originally appeared in Penn Engineering Today.

Penn Integrates Knowledge Professor Kevin Johnson Takes the Stage at ‘Engaging Minds’

by Michele Berger

Penn Integrates Knowledge Professor Kevin Johnson takes the stage at 24th Engaging Minds. (Image: Ben Asen)

This past weekend in New York City, the University of Pennsylvania showcased its 24th Engaging Minds event, the first in person since 2019. It was hosted by Penn Alumni.

Three Penn Integrates Knowledge University Professors — Kevin JohnsonLance Freeman and Dolores Albarracín, — each discussed their research. The audience, at least 600 in person and remote, heard about using city planning to promote racial equity, about how conspiracy theories come to life and propagate, and about the need for physicians to communicate effectively with patients and families.

Following brief remarks from Penn Alumni President Ann Reese, University President Liz Magill introduced the event. “As many of you know, I’ve been thinking a lot and speaking often about what makes Penn Penn,” she said. “What are our distinctive strengths? What are the unique contributions to society that we have made in the past and can make in the future? And where do we go from the extraordinary position we are in now?”

Magill went on to express gratitude for the speakers and invited the audience to think about how the researchers’ work and expertise furthered what she described as the “twin principles of truth and opportunity.”

Effective communication

Johnson, the David L. Cohen University Professor with joint appointments in the Department of Computer and Information Science in the School of Engineering and Applied Science, and the Department of Biostatistics, Epidemiology, and Informatics in the Perelman School of Medicine, started his talk with a case study. “That case is going to be my case,” he said.

He took the audience through his family history, education and training, pausing at a point on the timeline when he was a young physician-scientist who had just explained a new medical topic to a journalist. “I felt really good about the conversation — and then the article came out,” Johnson said.

In the piece, he had been cast as saying that the medical community was over-treating this condition, “which is not what I said.” He realized in that moment that as a physician, he had been taught to communicate what a study finds, not how to act based on those findings. That experience shifted his thinking on how to communicate scientific topics, and he has spent decades trying to move the needle on how others in his field perceive this.

“As scientists we face obstacles. We face the obstacle of scale, so, small projects that we’re asked to generalize. We face the issue of trust. And then we face the issue of values,” Johnson said. “I’ll add a fourth, which is format; the way we choose to reach specific audiences will be different.”

Read more about the 24th Engaging Minds at Penn Today.

Kevin Johnson is the David L. Cohen University of Pennsylvania Professor in the Departments of Biostatistics, Epidemiology and Informatics and Computer and Information Science. As a Penn Integrates Knowlegde (PIK) University Professor, Johnson also holds appointments in the Departments of Bioengineering and Pediatrics, as well as in the Annenberg School of Communication.