Five University of Pennsylvania undergraduates have received 2022 Goldwater Scholarships, including Laila Barakat Norford, a third year Bioengineering major from Wayne, Pennsylvania. Goldwater Scholarships are awarded to sophomores or juniors planning research careers in mathematics, the natural sciences, or engineering.
Penn has produced 23 Goldwater Scholars in the past seven years and a total of 55 since Congress established the scholarship in 1986.
Laila Barakat Norford is majoring in bioengineering with minors in computer science and bioethics in Penn Engineering. As a Rachleff Scholar, Norford has been engaged in systems biology research since her first year. Her current research uses machine learning to predict cell types in intestinal organoids from live-cell images, enabling the mechanisms of development and disease to be characterized in detail. At Penn, she is an Orientation Peer Advisor, a volunteer with Advancing Women in Engineering and the Penn Society of Women Engineers, and a teaching assistant for introductory computer science. She is secretary of the Penn Band, plays the clarinet, and is a member of the Band’s Fanfare Honor Society for service and leadership. Norford registers voters with Penn Leads the Vote and canvasses for state government candidates. She is also involved in Penn’s LGBTQ+ community as a member of PennAces. Norford plans to pursue a Ph.D. in computational biology, aspiring to build computational tools to address understudied diseases and health disparities.
Team Ossum is comprosed of Ananya Dewan (Vagelos LSM), Hoang Le (Vagelos LSM), Shiva Teerdhala (Vagelos LSM), Karan Shah (SEAS), and Savan Patel (M&T). Karan and Savan are both bioengineering majors. Their winning pitch to a panel of expert judges proposed “a commercial application to remove obstacles to safe cerclage use in orthopedic fracture fixation with Penn’s steerable needle technology.” Initial work for Ossum’s device, OsPass, was done in the George H. Stephenson Foundation Educational Laboratory & Bio-MakerSpace, the primary teaching lab and interdisciplinary makerspace of the Department of Bioengineering which is open to any Penn students campus-wide.
Team Steed, who proposed “an application to make breast biopsies less painful and damaging,” placed among the competition finalists and included bioengineering majors Farhaanah Mohideen, Ananyaa Kumar, and Kristina Khaw.
The Penn researchers’ latest paper on the design of lipid nanoparticles was featured on the cover of the most recent edition of the journal Nano Letters.
From COVID vaccines to cancer immunotherapies to the potential for correcting developmental disorders in utero, mRNA-based approaches are a promising tool in the fight against a wide range of diseases. These treatments all depend on providing a patient’s cells with genetic instructions for custom proteins and other small molecules, meaning that getting those instructions inside the target cells is of critical importance.
The current delivery method of choice uses lipid nanoparticles (LNPs). Thanks to surfaces customized with binding and signaling molecules, they encapsulate mRNA sequences and smuggle them through the cell membrane. But with a practically unlimited number of variables in the makeup of those surfaces and molecules, figuring out how to design the most effective LNP is a fundamental challenge.
Now, in a study featured on the cover of the journal Nano Letters, researchers from the University of Pennsylvania’s School of Engineering and Applied Science and Perelman School of Medicine have now shown how to computationally optimize the design of these delivery vehicles.
Using an established methodology for comparing a wide range of variables known as “orthogonal design of experiments,” the researchers simultaneously tested 256 candidate LNPs. They found the frontrunner was three times better at delivering mRNA sequences into T cells than the current standard LNP formulation for mRNA delivery.
The study was led by Michael Mitchell, Skirkanich Assistant Professor of Innovation in the Department of Bioengineering in Penn’s School of Engineering and Applied Science, and Margaret Billingsley, a graduate student in his lab.
A scanning electron micrograph of a healthy human T cell. A better understanding the wide variety of antigen receptors that appear on the surfaces of these critical components of the immune system is necessary for improving a new class of therapies. (Credit: NIAID)
Our bodies are equipped with specialized white blood cells that protect us from foreign invaders, such as viruses and bacteria. These T cells identify threats using antigen receptors, proteins expressed on the surface of individual T cells that recognize specific amino acid sequences found in or on those invaders. Once a T cell’s antigen receptors bind to the corresponding antigen, it can directly kill infected cells or call for backup from the rest of the immune system.
We have hundreds of billions of T cells, each with unique receptors that recognize unique antigens, so profiling this T cell antigen specificity is essential in our understanding of the immune response. It is especially critical in developing targeted immunotherapies, which equip T cells with custom antigen receptors that recognize threats they would otherwise miss, such as the body’s own mutated cancer cells.
Jenny Jiang, Ph.D.
Jenny Jiang, Peter and Geri Skirkanich Associate Professor of Innovation in Bioengineering, along with lab members and colleagues at the University of Texas, Austin, recently published a study in Nature Immunology that describes their technology, which simultaneously provides information in four dimensions of T cell profiling. Ke-Yue Ma and Yu-Wan Guo, a former post doc and current graduate student in Jiang’s Penn Engineering lab, respectively, also contributed to this study.
This technology, called TetTCR-SeqHD, is the first to provide such detailed information about single T cells in a high-throughput manner, opening doors for personalized immune diagnostics and immunotherapy development.
There are many pieces of information needed to comprehensively understand the immune response of T cells, and gathering all of these measurements simultaneously has been a challenge in the field. Comprehensive profiling of T cells includes sequencing the antigen receptors, understanding how specific those receptors are in their recognition of invading antigens, and understanding T cell gene and protein expression. Current technologies only screen for one or two of these dimensions due to various constraints.
“Current technologies that measure T cell immune response all have limitations,” says Jiang. “Those that use cultured or engineered T cells cannot tell us about their original phenotype, because once you take a cell out of the body to culture, its gene and protein expression will change. The technologies that address T cell and antigen sequencing with mass spectrometry damage genetic information of the sample. And current technologies that do provide information on antigen specificity use a very expensive binding ligand that can cost more than a thousand dollars per antigen, so it is not feasible if we want to look at hundreds of antigens. There is clearly room for advancement here.”
The TetTCR-SeqHD technology combines Jiang’s previously developed T cell receptor sequencing tool, TetTCR-Seq, described in a Nature Biotechnology paper published in 2018, with the new ability of characterizing both gene and protein expression.
Joseph Lance Casila, a doctoral student and Fontaine Fellow in Bioengineering, was profiled by his alma mater, the University of Guam (UOG. Casila was the first person in his family to graduate from a U.S.-accredited university and is now studying tissue engineering and regenerative medicine in the Bioengineering and Biomaterials Laboratory of Riccardo Gottardi, Assistant Professor in Bioengineering in Penn Engineering and Pediatrics in Penn Medicine and the Children’s Hospital of Philadelphia (CHOP). His research in the Gottardi lab employs “tissue engineering and drug delivery for biomedical problems relating to knees, ears, nose, and throat but specifically to pediatric airway disorders.” The article discusses Casila’s journey from valedictorian of his high school, to a first-generation undergraduate interested bioengineering, and now a graduate student studying at Penn on a full scholarship. After completing his degree, Casila hopes to bring what he’s learned back home to advance health care in Guam.
“My mentors, and especially my friends, helped me make the most of what UOG had to offer, and it paid off rewardingly,” he said. “You get what you put in.”
Kariyawasam is a double major in Engineering’s Department of Bioengineering, with concentrations in computational medicine and medical devices, and in the Wharton School, with concentrations in finance and entrepreneurship and innovation.
“We are so proud of our newest Penn Rhodes Scholars who have been chosen for this tremendous honor and opportunity,” said President Amy Gutmann. “The work Raveen has done in health care innovation and accessibility and Nicholas has done to support student well-being while at Penn is impressive, and pursuing a graduate degree at Oxford will build upon that foundation. We look forward to seeing how they make an impact in the future.”
The Rhodes is highly competitive and one of the most prestigious scholarships in the world. The scholarships provide all expenses for as long as four years of study at Oxford University in England.
According to the Rhodes Trust, about 100 Rhodes Scholars will be selected worldwide this year, chosen from more than 60 countries. Several have attended American colleges and universities but are not U.S. citizens and have applied through their home country, including Kariyawasam in Sri Lanka.
Four of Penn’s 2021 iGEM team (left to right): Juliette Hooper, Grace Qian, Saachi Datta, and Gloria Lee.
The University of Pennsylvania’s 2021 iGEM team has been awarded several distinctions in this year’s highly competitive iGEM Competition. The International Genetically Engineered Machine Competition is the largest synthetic biology community and the premiere synthetic biology competition for both university and high school level students from around the world. Each year, hundreds of interdisciplinary teams of students combine molecular biology techniques and engineering concepts to create novel biological systems and compete for prizes and awards through oral presentations and poster sessions.
The Penn team’s project, “OptoReader,” is a combined light-simulation device and plate reader, which makes optogenetic experiments more powerful and accessible. The abstract reads:
“Metabolic engineering has the potential to change the world, and optogenetic tools can make metabolic engineering research easier by providing spatiotemporal control over cells. However, current optogenetic experiments are low-throughput, expensive, and laborious, which makes them inaccessible to many. To tackle this problem, we combined a light-stimulation device with a plate reader, creating our OptoReader. This device allows us to automate ~100 complex optogenetic experiments at the same time. Because it is open source and inexpensive, our device would make optogenetic experiments more efficient and available to all.”
This year’s Penn team was mentored by Lukasz Bugaj, Assistant Professor in Bioengineering. In addition, the team was supported by Brian Chow, Associate Professor in Bioengineering. Chow has supported previous undergraduate iGEM teams at Penn, and was involved in the creation of the iGEM program during his time as a graduate student at MIT.
OptoReader took home the top prizes in three of the four categories in which it was nominated. These prizes include:
Best Foundational Advance (best in track)
Best Hardware (best from all undergraduate teams)
Best Presentation (best from all undergraduate teams)
They were also awarded a Gold Medal Distinction and were included in the Top 10 Overall (from all undergraduate teams, and the only team from the United States to make the top 10) and Top 10 Websites (from all undergraduate teams).
The awards were announced during iGEM’s online Jamboree Award Ceremony on November 14, 2021 (watch the full award ceremony here).
In addition to the outstanding awards recognition, OptoReader was also selected for an iGEM Impact Grant which awards teams $2,500 to continue development of their projects. This new initiative from the iGEM Foundation was announced earlier this year, and with the support of the Frederick Gardner Cottrell Foundation, is distributing a total of $225,000 in grant funds to 90 iGEM teams during the 2021 competition season. Learn more about the Impact Grant and read the full list of winning teams here.
Penn’s 2021 iGEM team was made up of an interdisciplinary group of women undergraduates from the School of Engineering and Applied Science (SEAS) and the School of Arts and Sciences (SAS):
Saachi Datta (B.A. in Biology and Religious Studies 2021)
Juliette Hooper (B.S.E. and M.S.E. in Bioengineering 2022)
Gabrielle Leavitt (B.S.E. in Bioengineering 2021 and current Master’s student in Bioengineering)
Gloria Lee (B.A. in Physics and B.S.E. in Bioengineering 2023)
Grace Qian (B.S.E. in Bioengineering 2023)
Lana Salloum (B.A. in Neuroscience 2022)
They were mentored by three doctoral students in Bioengineering: Will Benman (Bugaj Lab), David Gonzalez Martinez (Bugaj Lab), Gabrielle Ho (Chow Lab). Saurabh Malani, a graduate student in the Avalos Lab at Prince University, was also very involved in mentoring the team.
OptoReader
The graduate mentors were instrumental in quickly bringing the undergraduates up to speed on a diverse array of skills needed to accomplish this project including circuit design, optics, optogenetics, programming, and additive manufacturing. They then coached the team through building and testing prototypes, as well as accomplishing other objectives required for success at iGEM. These other objectives included establishing collaborations with other iGEM teams, performing outreach, and effectively communicating their project through a website and online presentations.
“This team and their work is outstanding,” said William Benman. “Not only did they sweep several awards, but they did it all with a small team and while working with technology they had no prior experience with. They created a device that not only increases accessibility to optogenetics but also allows optogenetic systems to interface directly with computer programs, allowing for completely new research avenues within the field. They are truly a remarkable group.”
Due to the COVID pandemic, the team operated virtually through the summer of 2020, and then continued in person in the summer of 2021 as the project progressed and more students returned to Penn’s campus. Upon return to campus, the work was conducted in both the Bugaj lab in the Stephenson Foundation Educational Laboratory & Bio-MakerSpace, the primary teaching laboratory in Penn Bioengineering and an interdisciplinary makerspace open to anyone at Penn. The team also collaborated with the Avalos Lab at Princeton University, which conducts research in the application of optogenetics to optimize production of valuable chemicals in microbes.
“I’m beyond excited about this phenomenal showing from team Penn at the iGEM Jamboree awards ceremony,” said faculty mentor Lukasz Bugaj. “This is truly outstanding recognition for what the team has accomplished, and it wouldn’t have happened without essential contributions from everyone on the team.”
Brian Chow added that this achievement is “no small feat,” especially for a hardware project. “The iGEM competition leans toward genetic strain engineering, but the advances in the field made by these incredible students were undeniable,” he said.
Going forward, the team plans to publish a scientific article and file a patent application describing their device. “It’s clear that there is excitement in the scientific community for what our students created, and we’re excited to share the details and designs of their work,” said Bugaj.
Congratulations to all the team members and mentors of OptoReader on this incredible achievement! Check out the OptoReader project website and Instagram to learn more about their project.
Catherine Michelutti (SEAS/WHARTON ’23) working on her internship in her backyard with her dog
Catherine Michelutti, a junior in Bioengineering and Wharton and fellow in the Stavros Niarchos Foundation (SNF) Paideia Program, shared her virtual internship experience with the Orion Organisation, a healthcare NGO based in South Africa that provides for “the educational, training and therapeutic needs of children, youth and adults living with physical, psychosocial challenges, intellectual and neurological disabilities”:
“My internship with the Orion Organization has prompted me to reflect on my identity in terms of where my passions and future career interests lie. My previous work experiences have all been in biomedical research fields, which is something I’m passionate about and want to continue doing throughout my career. However, working with Orion has opened my eyes to the realms of interdisciplinary work that comes with operating a healthcare NGO and the joys that come with it.”
As a child, Sonal Mahindroo would go to her orthopaedics appointments with her family, slowly becoming more and more fascinated by the workings and conditions of the musculoskeletal system. While being treated for scoliosis, she would receive children’s books from her doctor that helped provide clear and simplified explanations of orthopaedic topics, which supported her interest.
Nearly a decade later, Mahindroo is still interested in expanding her orthopaedic knowledge, and a Penn Medicine program is helping fuel that expansion. Now a senior at St. Bonaventure University in New York, Mahindroo spends her time at the university’s lab. But in addition to that, this year, she was able to take part in more learning opportunities with Penn Medicine’s support, via the McKay Orthopaedic Research Lab’s Diversity, Equity, and Inclusion (DEI) committee’s conference grant program.
McKay’s DEI committee — consisting of faculty, post-docs, graduate students, and staff — offers a welcoming environment and resources that support people of all identities, empowering them to bring forward unique perspectives to orthopaedic research.
“Our goal is to improve diversity and culture both within McKay and in the orthopaedic research community outside of Penn,” said Sarah Gullbrand, PhD, a research assistant professor at the McKay Lab. “We wanted to provide an opportunity for students to attend a conference and make connections to help them pursue their interest in orthopaedic research.”
The McKay conference grant supports undergraduate students who have been unable to get hands-on research experience. Participants are provided with the opportunity to network with leaders in the field of orthopaedic research, listen to cutting-edge research presentations, and learn about ways to get involved in orthopaedic research themselves.
“When launching the conference grant program earlier this year, I was motivated by my own experience attending a conference as an undergraduate. That experience really increased my interest in attending graduate school and taught me a lot about the breadth of research in orthopaedics,” said Hannah Zlotnick, a PhD student at the McKay Lab and member of the DEI committee. Through the McKay Conference Grants, the committee has supported two cohorts of students. “So far, we’ve been able to fund 11 undergraduate students from around the country to virtually attend orthopaedics conferences and receive early exposure to careers in STEM.”
Along with the conference grant, the McKay Lab holds workshops, book clubs, and other programs focused on DEI-related topics. As part of their efforts for promoting gender diversity in the field, the McKay Lab has previously partnered with the Perry Initiative to offer direct orthopaedic experiences for girls in high school, where they can learn how to suture, and perform mock fracture fixation surgeries on sawbones.
As a primarily male-populated field, orthopaedics could benefit greatly from diversity efforts. While women comprise approximately 50 percent of medical school graduates in the United States, they represent only 14 percent of orthopaedic surgery residents.
“The only women on staff at my orthopaedist’s office were receptionists. There were no female physicians or engineers to make my scoliosis brace,” Mahindroo said. “It was really cool coming to the McKay Lab and seeing how much the field has progressed since then.”
N.B. Hannah Zlotnick is a PhD student in Bioengineering studying in the lab of Robert Mauck, Mary Black Ralston Professor in Bioengineering and Orthopaedic Surgery.
A decade ago, the National Science Foundation started its Innovation Corps program to help translate academic research into the wider world. Functioning as a national start-up accelerator, I-Corps provides training and funding to researchers who have a vision for applying their ideas, starting businesses and maximizing social impact.
Now, to further develop innovation ecosystems and share regional resources, the NSF has launched a network of five I-Corps Hubs.
Penn is a member of the Mid-Atlantic Hub, which will be led by the University of Maryland at College Park, and include Carnegie Mellon University, George Washington University, Howard University, Johns Hopkins University, North Carolina State University, Penn State, University of North Carolina at Chapel Hill, and Virginia Tech.
The Penn Center for Innovation is currently accepting applications to join the next I-Corps cohort, which begins in October 2021. Teams will receive up to $2,000 to support their start-up, and can apply online.
This story originally appeared in Penn Engineering Today.
N.B.: Founded by Penn alumna Katherine Sizov (Bio 2019) and winner of a 2019 President’s Innovation Prize, Strella Biotech seeks to reduce food waste through innovative biosensors, and was initially developed in the George H. Stephenson Foundation Educational Laboratory, the bio-makerspace and primary teaching lab of the Department of Bioengineering. Read more BE blog stories featuring Strella Biotechnology.
A decade ago, the National Science Foundation started its Innovation Corps program to help translate academic research into the wider world. Functioning as a national start-up accelerator, I-Corps provides training and funding to researchers who have a vision for applying their ideas, starting businesses and maximizing social impact.