The National Science Foundation’s Research Traineeship Program aims to support graduate students, educate the STEM leaders of tomorrow and strengthen the national research infrastructure. The program’s latest series of grants are going toward university programs focused on artificial intelligence and quantum information science and engineering – two areas of high priority in academia, industry and government.
Chinedum Osuji, Eduardo D. Glandt Presidential Professor and Chair of the Department of Chemical and Biomolecular Engineering (CBE), has received one of these grants to apply data science and machine learning to the field of soft materials. The grant will provide five years of support and a total of $3 million for a new Penn project on Data Driven Soft Materials Research.
Osuji will work with co-PIs Russell Composto, Professor and Howell Family Faculty Fellow in Materials Science and Engineering, Bioengineering, and in CBE, Zahra Fakhraai, Associate Professor of Chemistry in Penn’s School of Arts & Sciences (SAS) with a secondary appointment in CBE, Paris Perdikaris, Assistant Professor in Mechanical Engineering and Applied Mechanics, and Andrea Liu, Hepburn Professor of Physics and Astronomy in SAS, all of whom will help run the program and provide the connections between the multiple fields of study where its students will train.
These and other affiliated faculty members will work closely with co-PI Kristin Field, who will serve as Program Coordinator and Director of Education.
The Penn Center for Precision Engineering for Health (CPE4H) was established late last year to accelerate engineering solutions to significant problems in healthcare. The center is one of the signature initiatives for Penn’s School of Engineering and Applied Science and is supported by a $100 million commitment to hire faculty and support new research on innovative approaches to those problems.
Acting on that commitment, CPE4H solicited proposals during the spring of 2022 for seed grants of $80K per year for two years for research projects that address healthcare challenges in several key areas of strategic importance to Penn: synthetic biology and tissue engineering, diagnosis and drug delivery, and the development of innovative devices. While the primary investigators (PIs) for the proposed projects were required to have a primary faculty appointment within Penn Engineering, teams involving co-PIs and collaborators from other schools were eligible for support. The seed program is expected to continue for the next four years.
“It was a delight to read so many novel and creative proposals,” says Daniel A. Hammer, Alfred G. and Meta A. Ennis Professor in Bioengineering and the Inaugural Director of CPE4H. “It was very hard to make the final selection from a pool of such promising projects.”
Judged on technical innovation, potential to attract future resources, and ability to address a significant medical problem, the following research projects were selected to receive funding.
Evolving and Engineering Thermal Control of Mammalian Cells
Led by Lukasz Bugaj, Assistant Professor in Bioengineering, this project will engineer molecular switches that can be toggled on and off inside mammalian cells at near-physiological temperatures. Successful development of these switches will provide new ways to communicate with cells, an advance that could be used to make safer and more effective cellular therapies. The project will use directed evolution to generate and find candidate molecular tools with the desired properties. Separately, the research will also develop new technology for manipulating cellular temperature in a rapid and programmable way. Such devices will enhance the speed and sophistication of studies of biological temperature regulation.
A Quantum Sensing Platform for Rapid and Accurate Point-of-Care Detection of Respiratory Viral Infections
Combining microfluidics and quantum photonics, PI Liang Feng, Professor in Materials Science and Engineering and Electrical and Systems Engineering, Ritesh Agarwal, Professor in Materials Science Engineering, and Shu Yang, Joseph Bordogna Professor in Materials Science and Engineering and Chemical and Biomolecular Engineering, are teaming up with Ping Wang, Professor of Pathology and Laboratory Medicine in Penn’s Perelman School of Medicine, to design, build and test an ultrasensitive point-of-care detector for respiratory pathogens. In light of the COVID-19 pandemic, a generalizable platform for rapid and accurate detection of viral pathogenesis would be extremely important and timely.
Versatile Coacervating Peptides as Carriers and Synthetic Organelles for Cell Engineering
PI Amish Patel, Associate Professor in Chemical and Biomolecular Engineering, and Matthew C. Good, Associate Professor of Cell and Developmental Biology in the Perelman School of Medicine and in Bioengineering, will design and create small proteins that self-assemble into droplet-like structures known as coacervates, which can then pass through the membranes of biological cells. Upon cellular entry, these protein coacervates can disassemble to deliver cargo that modulates cell behavior or be maintained as synthetic membraneless organelles. The team will design new chemistries that will facilitate passage across cell membranes, and molecular switches to sequester and release protein therapeutics. If successful, this approach could be used to deliver a wide range of macromolecule drugs to cells.
Towards an Artificial Muscle Replacement for Facial Reanimation
Cynthia Sung, Gabel Family Term Assistant Professor in Mechanical Engineering and Applied Mechanics and Computer Information Science, will lead a research team including Flavia Vitale, Assistant Professor of Neurology and Bioengineering, and Niv Milbar, Assistant Instructor in Surgery in the Perelman School of Medicine. The team will develop and validate an electrically driven actuator to restore basic muscle responses in patients with partial facial paralysis, which can occur after a stroke or injury. The research will combine elements of robotics and biology, and aims to produce a device that can be clinically tested.
“These novel ideas are a great way to kick off the activities of the center,” says Hammer. “We look forward to soliciting other exciting seed proposals over the next several years.”
In 2005, John Ioannidis published a bombshell paper titled “Why Most Published Research Findings Are False.” In it, Ioannidis argued that a lack of scientific rigor in biomedical research — such as poor study design, small sample sizes and improper assessment of the significance of data— meant that a large percentage of experiments would not return the same results if they were conducted again.
Since then, researchers’ awareness of this “replication crisis” has grown, especially in fields that directly impact the health and wellbeing of people, where lapses in rigor can have life-or-death consequences. Despite this attention and motivation, however, little progress has been made in addressing the roots of the problem. Formal training in rigorous research practices remains rare; while mentors advise their students on how to properly construct and conduct experiments to produce the most reliable evidence, few educational resources exist to support them.
Konrad Kording, a Penn Integrates Knowledge Professor with appointments in the Departments of Bioengineering and Computer and Information Science in Penn Engineering and the Department of Neuroscience in Penn’s Perelman School of Medicine, has been awarded one of the initiative’s first five grants.
“The replication crisis is real,” says Kording. “I’ve tried to replicate the research of others and failed. I’ve reanalyzed my own data and found major mistakes that needed to be corrected. I was never properly taught how to do rigorous science, and I want to improve that for the next generation.”
Our body’s natural line of defense against infection and disease, as well as cancer, is our immune system equipped with T cells, a type of white blood cell that determines how we react to foreign substances, or antigens, in the body. While we have an arsenal of T cells to protect us from these various infections, some people lack certain T cells or simply do not have enough to fight off infections, such as the flu or HIV, or defend against the body’s own mutated cancer cells.
Understanding the diversity of T cells and which antigens they target can provide insight into developing personalized immunotherapy to help those patients with weak spots or gaps in their T cell community. Jenny Jiang, Peter and Geri Skirkanich Associate Professor of Innovation in Bioengineering, is characterizing this diversity.
Jiang recently received a Cancer Research Institute’s (CRI) Lloyd J. Old STAR grant to support her research on this topic. The CRI STAR grant identifies mid-career “Scientists TAking Risks” in innovative cancer immunotherapy research areas, providing freedom and flexibility to pursue high-risk, high-reward research with financial support of $1.25 Million over the course of five years.
Jiang spoke with CRI science writer Arthur Brodsky about her research and how the STAR grant will support it.
“In our studies of healthy individuals, who have some natural immune protection against commonly encountered viruses like the flu, we noticed that not everyone has T cells that cover all the possible antigens,” says Jiang. “There are differences in the number and types of flu-targeting T cells that each individual has. For some “exotic” antigens, like those of HIV for example, although the general population doesn’t actually have exposure to them, they should still have a very low level of minimum T cells that can offer some protection from possible future infection. So that part of our T cell arsenal acts as a safety net. But some individuals may completely lack those T cells. In those cases, as you can imagine, those people will have a hard time overcoming a future infection.”
Jiang describes how this is similar to how our bodies prevent cancerous tumor growth.
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.
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.
Rechargeable lithium-ion batteries are becoming more ubiquitous, thanks to their use in emerging applications such as battery electric vehicles and grid-scale energy storage, however, these batteries are inefficiently manufactured and unsustainably sourced.
The typical battery cell consists of a separator membrane filled with liquid electrolyte, sandwiched between the negative anode and positive cathode. This design has several drawbacks, including a complex and energy-intensive manufacturing process, inefficient recycling, and increased safety risks as the liquid electrolyte is flammable and crystallization between the electrodes can lead to explosions. Finally, there are substantial geopolitical and environmental risks associated with the global supply chain for lithium-ion battery materials, such as cobalt and lithium.
The solid-state battery design addresses these issues. In solid-state batteries, the flammable liquid electrolyte is replaced by a solid electrolyte, making them safer and more energy efficient. Sodium-ion batteries address the issue of sustainable material sourcing as sodium is more abundant than lithium and cobalt, the materials used in lithium-ion batteries. Both solid-state lithium-ion batteries and sodium-ion batteries are very attractive for battery electric vehicles and grid-scale energy storage applications.
However, current solid-state battery designs also suffer from two major drawbacks: a low capacity for power storage and a resistance to charge transfer.
To tackle the unsustainability in battery materials and the inefficiency of the current solid-state design, the National Science Foundation has awarded a team of Penn Engineers $2.7 Million in funding through its Future Manufacturing program. The team will be led by Eric Detsi, Stephenson Term Assistant Professor in the Department of Materials Science and Engineering (MSE), and will include Eric Stach, Professor in MSE and Director of the Laboratory for Research on the Structure of Matter, and Russell Composto, Howell Family Faculty Fellow and Professor in MSE with appointments in the Departments of Bioengineering and Chemical and Biomolecular Engineering.
“Our team will investigate a novel ‘Eco Manufacturing’ route to a 3D solid-state sodium-ion battery based on polymer solid-electrolytes,” says Detsi. “Our Eco Manufacturing approach will enable us to create batteries from only abundant elements, achieve ultralong battery cycle life, prevent sodium-dendrite-induced short-circuiting by using a ‘self-healing’ metal anode that can transform into liquid when the battery is operating, and efficiently recycle the battery’s anode and cathode. We will also improve the manufacturing process by using time- and energy-efficient processes including direct ink writing, solid-state conversion, and infiltration.”
COVID-19 vaccines are just the beginning for mRNA-based therapies; enabling a patient’s body to make almost any given protein could revolutionize care for other viruses, like HIV, as well as various cancers and genetic disorders. However, because mRNA molecules are very fragile, they require extremely low temperatures for storage and transportation. The logistical challenges and expense of maintaining these temperatures must be overcome before mRNA therapies can become truly widespread.
With these challenges in mind, Penn Engineering researchers are developing a new manufacturing technique that would be able to produce mRNA sequences on demand and on-site, isolating them in a way that removes the need for cryogenic temperatures. With more labs able to make and store mRNA-based therapeutics on their own, the “cold chain” between manufacturer and patient can be made shorter, faster and less expensive.
The National Science Foundation (NSF) is supporting this project, known as Distributed Ribonucleic Acid Manufacturing, or DReAM, through a four-year, $2 million grant from its Emerging Frontiers in Research and Innovation (EFRI) program.
The project will be led by Daeyeon Lee, Evan C Thompson Term Chair for Excellence in Teaching and Professor in the Department of Chemical and Biomolecular Engineering (CBE), along with Kathleen Stebe, Richer and Elizabeth Goodwin Professor in CBE and in the Department of Mechanical Engineering and Applied Mechanics. They will collaborate with Michael Mitchell, Skirkanich Assistant Professor of Innovation in the Department of Bioengineering, Drexel University’s Masoud Soroush and Michael Grady, the University of Oklahoma’s Dimitrios Papavassiliou and the University of Colorado Boulder’s Joel Kaar.
Jenny Jiang, the Peter & Geri Skirkanich Associate Professor of Innovation in the department of Bioengineering, has received a Lloyd J. Old STAR Program grant from the Cancer Research Institute (CRI), which is a major supporter of cancer immunotherapy research and clinical trials with the goal of curing all types of cancer.
The CRI Lloyd J. Old Scientists Taking Risks (STAR) Program “provides long-term funding to mid-career scientists, giving them the freedom and flexibility to pursue high-risk, high-reward research at the forefront of discovery and innovation in cancer immunotherapy.” This prestigious grant was give to six awardees this year, chosen from a pool of hundreds of applicants, and recognizes “future leaders in the field of cancer immunotherapy [who are expected to] carry out transformational research.”
The Old STAR Program Grant comes with $1.25 million in funding over 5 years to support the awardees’ cancer immunology research.
Jiang, who recently joined Penn Bioengineering, is a pioneer in developing tools in genomics, biophysics, immunology, and informatics and applying them to study systems immunology and immune engineering in human diseases. She was also inducted into the American Institute for Medical and Biological Engineering (AIMBE) College of Fellows in March 2021 for her outstanding contributions to the field of systems immunology and immunoengineering and devotion to the success of women in engineering. Jiang’s research focuses on systems immunology by developing technologies that enable high-throughput, high-content, single cell profiling of T cells in health and disease and she is recognized as one of the leading authorities in systems immunology and immunoengineering.
“The STAR Award from CRI allows my lab to answer some of the fundamental questions in T cell biology, such as is the T cell repertoire complete to cover all possible cancer antigens, as well as to improve the efficacy of T cell based cancer immunotherapies,” says Jiang.
With the goal of supporting partnerships between minority-serving educational institutions and leading materials science research centers, NSF’s Partnership for Research & Education in Materials (PREM) program funds innovative research programs and provides institutional support to increase recruitment, retention, and graduation by underrepresented groups as well as providing underserved communities access to materials research and education.
‘Research at the frontier’
With this PREM award, known as the Advancing Device Innovation through Inclusive Research and Education (ADIIR) program, researchers from Penn and UPR’s Humacao and Cayey campuses will conduct research on the properties of novel carbon-based materials with unique properties, and will study the effects of surface modification in new classes of sensors, detectors, and purification devices.
Thanks to this collaboration of more than 20 years, both institutions have made significant scientific and educational progress aided by biannual symposia and regular pre-pandemic travel between both institutions before the pandemic, resulting in a rich portfolio of publications, conference presentations, patents, students trained, and outreach programs.
“Together we have been publishing good papers that have impact, and we’ve really cultivated a culture of collaboration and friendship between our institutions,” says Penn’s Arjun Yodh, former director of the LRSM. “Our goal is to carry out research at the frontier and, in the process, nurture promising students from Puerto Rico and Penn.”
Ivan Dmochowski, a chemistry professor at Penn who has been involved with PREM for several years, says that this program has helped his group connect with experts in Puerto Rico whose skills complement his group’s interests in protein engineering. Dmochowski has also hosted UPR faculty members and students in his lab and also travelled to Puerto Rico before the pandemic to participate in research symposia, seminars, and outreach events.
“I’ve had students who have benefitted from being a co-author on a paper or having a chance to mentor students, and the faculty we’ve interacted with are exceptional,” Dmochowski says. “There’s a lot of benefit for both me and my students, and I’ve enjoyed our interactions both personally and scientifically.”
Penn’s Daeyeon Lee, a chemical and biomolecular engineering professor who has been involved with PREM for several years, regularly hosts students and faculty from UPR while working on nanocarbon-based composite films for sensor applications. The success of this collaboration relies on unique materials made by researchers at UPR combined with a method for processing them into composite structures developed in Lee’s lab.
“What I really admire about people at PREM, both faculty and students, is their passion,” says Lee. “I think that’s had a really positive impact on my students and postdocs who got to interact with them because they got to see the passion that the students brought.”
The National Science Foundation’s CAREER Award is given to early-career researchers in order to kickstart their careers in innovative and pivotal research while giving back to the community in the form of outreach and education. Alex Hughes, Assistant Professor in Bioengineering and in Cell and Developmental Biology, is among the Penn Engineering faculty members who have received the CAREER Award this year.
Hughes plans to use the funds to develop a human kidney model to better understand how the development of cells and tissues influences congenital diseases of the kidney and urinary tract.
The model, known as an “organoid,” is a lab-grown piece of human kidney tissue on the scale of millimeters to centimeters, grown from cultured human cells.
“We want to create a human organoid structure that has nephrons, the filters of the kidney, that are properly ‘plumbed’ or connected to the ureteric epithelium, the tubules that direct urine towards the bladder,” says Hughes. “To achieve that, we have to first understand how to guide the formation of the ureteric tubule networks, and then stimulate early nephrons to fuse with those networks. In the end, the structures will look like ‘kidney subunits’ that could potentially be injected and fused to existing kidneys.”
The field of bioengineering has touched on questions similar to those posed by Hughes, focusing on drug testing and disease treatment. Some of these questions can be answered with the “organ-on-a-chip” approach, while others need an even more realistic model of the organ. The fundamentals of kidney development and questions such as “how does the development of nephrons affect congenital kidney and urinary tract anomalies?” require an organoid in an environment as similar to the human body as possible.
“We decided to start with the kidney for a few reasons,” says Hughes. “First, because its development is a beautiful process; the tubule growth is similar to that of a tree, splitting into branches. It’s a complex yet understudied organ that hosts incredibly common developmental defects.
“Second,” he says, “the question of how things form and develop in the kidney has major medical implications, and we cannot answer that with the ‘organ-on-a-chip’ approach. We need to create a model that mimics the chemical and mechanical properties of the kidney to watch these tissues develop.”
The fundamental development of the kidney can also answer other questions related to efficiency and the evolution of this biological filtration system.
“We have the tendency to believe that systems in the human body are the most evolved and thus the most efficient, but that is not necessarily true,” says Hughes. “If we can better understand the development of a system, such as the kidney, then we may be able to make the system better.”
Hughes’ kidney research will lay the foundation for broader goals within regenerative medicine and organ transplantation.