Penn Researchers Show ‘Encrypted’ Peptides Could be Wellspring of Natural Antibiotics

by Melissa Pappas

César de la Fuente, Ph.D.

While biologists and chemists race to develop new antibiotics to combat constantly mutating bacteria, predicted to lead to 10 million deaths by 2050, engineers are approaching the problem through a different lens: finding naturally occurring antibiotics in the human genome.

The billions of base pairs in the genome are essentially one long string of code that contains the instructions for making all of the molecules the body needs. The most basic of these molecules are amino acids, the building blocks for peptides, which in turn combine to form proteins. However, there is still much to learn about how — and where — a particular set of instructions are encoded.

Now, bringing a computer science approach to a life science problem, an interdisciplinary team of Penn researchers have used a carefully designed algorithm to discover a new suite of antimicrobial peptides, hiding deep within this code.

The study, published in Nature Biomedical Engineering, was led by César de la Fuente, Presidential Assistant Professor in Bioengineering, Microbiology, Psychiatry, and Chemical and Biomolecular Engineering, spanning both Penn Engineering and Penn Medicine, and his postdocs Marcelo Torres and Marcelo Melo. Collaborators Orlando Crescenzi and Eugenio Notomista of the University of Naples Federico II also contributed to this work.

“The human body is a treasure trove of information, a biological dataset. By using the right tools, we can mine for answers to some of the most challenging questions,” says de la Fuente. “We use the word ‘encrypted’ to describe the antimicrobial peptides we found because they are hidden within larger proteins that seem to have no connection to the immune system, the area where we expect to find this function.”

Read the full story in Penn Engineering Today.

A New Model for How the Brain Perceives Unique Odors

by Erica K. Brockmeier

Cathy and Marc Lasry Professor Vijay Balasubramanian at Penn’s BioPond.

A study published in PLOS Computational Biology describes a new model for how the olfactory system discerns unique odors. Researchers from the University of Pennsylvania found that a simplified, statistics-based model can explain how individual odors can be perceived as more or less similar from others depending on the context. This model provides a starting point for generating new hypotheses and conducting experiments that can help researchers better understand the olfactory system, a complex, crucial part of the brain.

The sense of smell, while crucial for things like taste and hazard avoidance, is not as well studied as other senses. Study co-author Vijay Balasubramanian, a theoretical physicist with an interest in how living systems process information, says that olfaction is a prime example of a complex information-processing system found in nature, as there are far more types of volatile molecules—on the scale of tens or hundreds of thousands—than there are receptor types in the nose to detect them, on the scale of tens to hundreds depending on the species.

“Every molecule can bind to many receptors, and every receptor can bind to many molecules, so you get this combinatorial mishmash, with the nose encoding smells in a way that involves many receptor types to collectively tell you what a smell is,” says Balasubramanian. “And because there are many fewer receptor types than molecular species, you basically have to compress a very high dimensional olfactory space into a much lower dimensional space of neural responses.”

Read the full story in Penn Today.

Vijay Balasubramanian is the Cathy and Marc Lasry Professor in the Department of Physics & Astronomy in the School of Arts & Sciences at the University of Pennsylvania and a member of the Penn Bioengineering Graduate Group.

This research was supported by the Simons Foundation Mathematical Modeling of Living Systems (Grant 400425) and the Swartz Foundation.

NSF Grant Will Support Research into Sustainable Manufacturing of 3D Solid-state Sodium-ion Batteries and Battery Workforce Training

by Melissa Pappas

The Department of Materials Science and Engineering’s Eric Detsi will lead a team of researchers, including MSE’s Eric Stach and Russell Composto, to develop more eco-friendly batteries that are based on sodium, rather than lithium.

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.”

Read the full story in Penn Engineering Today.

Carl June Highlighted for Success in Gene Therapy

Carl June, MD

Scientific American recently featured two gene therapies that were invented at Penn, including research from Carl June, MD, the Richard W. Vague Professor in Immunotherapy in Pathology and Laboratory Medicine, director of the Center for Cellular Immunotherapies, and member of the Penn Bioengineering Graduate Group, which led to the FDA approval for the CAR T therapy (sold by Novartis as Kymriah) for treating acute lymphoblastic leukemia (ALL), one of the most common childhood cancers.

Read “Four Success Stories in Gene Therapy” in Scientific American.

Nerve Repair, With Help From Stem Cells

A cross-disciplinary Penn team is pioneering a new approach to peripheral nerve repair.

In a new publication in the journal npj Regenerative Medicine, a team of Penn researchers from the School of Dental Medicine and the Perelman School of Medicine “coaxed human gingiva-derived mesenchymal stem cells (GMSCs) to grow Schwann-like cells, the pro-regenerative cells of the peripheral nervous system that make myelin and neural growth factors,” addressing the need for regrowing functional nerves involving commercially-available scaffolds to guide nerve growth. The study was led by Anh Le, Chair and Norman Vine Endowed Professor of Oral Rehabilitation in the Department of Oral and Maxillofacial Surgery/Pharmacology at the University of Pennsylvania School of Dental Medicine, and was co-authored by D. Kacy Cullen, Associate Professor in Neurosurgery at the Perelman School of Medicine at Penn and the Philadelphia Veterans Affairs Medical Center and member of the Bioengineering Graduate Group:

D. Kacy Cullen (Image: Eric Sucar)

“To get host Schwann cells all throughout a bioscaffold, you’re basically approximating natural nerve repair,” Cullen says. Indeed, when Le and Cullen’s groups collaborated to implant these grafts into rodents with a facial nerve injury and then tested the results, they saw evidence of a functional repair. The animals had less facial droop than those that received an “empty” graft and nerve conduction was restored. The implanted stem cells also survived in the animals for months following the transplant.

“The animals that received nerve conduits laden with the infused cells had a performance that matched the group that received an autograft for their repair,” he says. “When you’re able to match the performance of the gold-standard procedure without a second surgery to acquire the autograft, that is definitely a technology to pursue further.”

Read the full story and view the full list of collaborators in Penn Today.

How a Diversity Program Enabled a Childhood Orthopaedics Patient’s Research Dreams

by Julie Wood

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.”

Read more at Penn Medicine News.

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.

Using Big Data to Measure Emotional Well-being in the Wake of George Floyd’s Murder

by Melissa Pappas

George Floyd’s murder had an undeniable emotional impact on people around the world, as evidenced by this memorial mural in Berlin, but quantifying that impact is challenging. Researchers from Penn Engineering and Stanford have used a computational approach on U.S. survey data to break down this emotional toll along racial and geographic lines. Their results show a significantly larger amount of self-reported anger and sadness among Black Americans than their White counterparts. (Photo: Leonhard Lenz)

The murder of George Floyd, an unarmed Black man who was killed by a White police officer, affected the mental well-being of many Americans. The effects were multifaceted as it was an act of police brutality and example of systemic racism that occurred during the uncertainty of a global pandemic, creating an even more complex dynamic and emotional response.

Because poor mental health can lead to a myriad of additional ailments, including poor physical health, inability to hold a job and an overall decrease in quality of life, it is important to understand how certain events affect it. This is especially critical when the emotional burden of these events  falls most on demographics affected by systemic racism. However, unlike physical health, mental health is challenging to characterize and measure, and thus, population-level data on mental health has been limited.

To better understand patterns of mental health on a population scale, Penn Engineers Lyle H. Ungar, Professor of Computer and Information Science (CIS), and Sharath Chandra Guntuku, Research Assistant Professor in CIS, take a computational approach to this challenge. Drawing on large-scale surveys as well as language analysis in social media through their work with the World Well-Being Project, they have developed visualizations of these patterns across the U.S.

Their latest study involves tracking changes in emotional and mental health following George Floyd’s murder. Combining polling data from the U.S. Census and Gallup, Guntuku, Ungar and colleagues have shown that Floyd’s murder spiked a wave of unprecedented sadness and anger across the U.S. population, the largest since relevant data began being recorded in 2009.

Read the full story in Penn Engineering Today.

N.B. Lyle Ungar is also a member of the Penn Bioengineering Graduate Group.

Atomically-thin, Twisted Graphene Has Unique Properties

by Erica K. Brockmeier

New collaborative research describes how electrons move through two different configurations of bilayer graphene, the atomically-thin form of carbon. These results provide insights that researchers could use to design more powerful and secure quantum computing platforms in the future.

New research published in Physical Review Letters describes how electrons move through two different configurations of bilayer graphene, the atomically-thin form of carbon. This study, the result of a collaboration between Brookhaven National Laboratory, the University of Pennsylvania, the University of New Hampshire, Stony Brook University, and Columbia University, provides insights that researchers could use to design more powerful and secure quantum computing platforms in the future.

“Today’s computer chips are based on our knowledge of how electrons move in semiconductors, specifically silicon,” says first and co-corresponding author Zhongwei Dai, a postdoc at Brookhaven. “But the physical properties of silicon are reaching a physical limit in terms of how small transistors can be made and how many can fit on a chip. If we can understand how electrons move at the small scale of a few nanometers in the reduced dimensions of 2-D materials, we may be able to unlock another way to utilize electrons for quantum information science.”

When a material is designed at these small scales, to the size of a few nanometers, it confines the electrons to a space with dimensions that are the same as its own wavelength, causing the material’s overall electronic and optical properties to change in a process called quantum confinement. In this study, the researchers used graphene to study these confinement effects in both electrons and photons, or particles of light.

The work relied upon two advances developed independently at Penn and Brookhaven. Researchers at Penn, including Zhaoli Gao, a former postdoc in the lab of Charlie Johnson who is now at The Chinese University of Hong Kong, used a unique gradient-alloy growth substrate to grow graphene with three different domain structures: single layer, Bernal stacked bilayer, and twisted bilayer. The graphene material was then transferred onto a special substrate developed at Brookhaven that allowed the researchers to probe both electronic and optical resonances of the system.

“This is a very nice piece of collaborative work,” says Johnson. “It brings together exceptional capabilities from Brookhaven and Penn that allow us to make important measurements and discoveries that none of us could do on our own.”

Read the full story in Penn Today.

Charlie Johnson is the Rebecca W. Bushnell Professor of Physics and Astronomy in the Department of Physics and Astronomy in the School of Arts & Sciences at the University of Pennsylvania and a member of the Penn Bioengineering Graduate Group.

Reimagining Scientific Discovery Through the Lens of an Artist

by Erica K. Brockmeier

Rebecca Kamen, Penn artist-in-residence and visiting scholar, has a new exhibition titled “Reveal: The Art of Reimagining Scientific Discovery” at American University Museum at the Katzen Arts Center that explores curiosity and the creative process across art and science. (Image: Greg Staley)

Rebecca Kamen, Penn artist-in-residence and visiting scholar, has long been interested in science and the natural world. As a Philadelphia native and an artist with a 40-plus-year career, her intersectional work sheds light on the process of scientific discovery and its connections to art, with previous exhibitions that celebrate Apollo 11’s “spirit of exploration and discovery” to new representations of the periodic table of elements.

Now, in her latest exhibition, Kamen has created a series of pieces that highlight how the creative processes in art and science are interconnected. In “Reveal: The Art of Reimagining Scientific Discovery,” Kamen chronicles her own artistic process while providing a space for self-reflection that enables viewers to see the relationship between science, art, and their own creativity.

The exhibit, on display at the Katzen Art Center at American University, was inspired by the work of Penn professor Dani Bassett and American University professor Perry Zurn, the exhibit’s faculty sponsor. The culmination of three years of work, “Reveal” features collaborations with a wide range of scientists, including philosophers at American University, microscopists at the National Institutes of Health studying SARS-CoV-2 , and researchers in Penn’s Complex Systems Lab and the Addiction, Health, and Adolescence (AHA!) Lab.

Continue reading at Penn Today.

Dani S. Bassett is the J. Peter Skirkanich Professor in the departments of Bioengineering and Electrical and Systems Engineering in the School of Engineering and Applied Science at the University of Pennsylvania. She also has appointments in the Department of Physics and Astronomy in Penn’s School of Arts & Sciences and the departments of Neurology and Psychiatry in the Perelman School of Medicine at Penn.

Rebecca Kamen is a visiting scholar and artist-in-residence in the Department of Physics & Astronomy in Penn’s School of Arts & Sciences.

David Lydon-Staley is an assistant professor in the Annenberg School for Communication at Penn and was formerly a postdoc in the Bassett lab.

Dale Zhou is a Ph.D. candidate in Penn’s Neuroscience Graduate Group.

“Reveal: The Art of Reimagining Scientific Discovery,” presented by the Alper Initiative for Washington Art and curated by Sarah Tanguy, is on display at the American University Museum in Washington, D.C., until Dec. 12.

The exhbition catalog, which includes an essay on “Radicle Curiosity” by Perry Zurn and Dani S. Bassett, can be viewed online.

Interact, Adapt, Repeat

Sophomores Linda Wu and Nova Meng spent the summer studying coevolution among plants, mutualistic bacteria, and parasitic nematodes in Corlett Wood’s biology lab.

by Katherine Unger Baillie

To study coevolution, the responsibilities of Nova Meng and Linda Wu included caring for plants in the Penn greenhouse. (Image: From July 2021, when masks were not required)

Coevolution is all around us. Think of the elongated blooms that perfectly accommodate a hummingbird’s slender mouth parts. But not all examples of species influencing one another’s evolutionary course accrue benefits to all parties. Tradeoffs are part of the game.

This summer, sophomores Linda Wu of Annandale, Virginia, and Nova Meng of Akron, Ohio, researched an coevolutionary scenario with benefits as well as costs for the species involved. Their work, supported by the Penn Undergraduate Research Mentoring Program (PURM) and conducted in the lab of biology professor Corlett Wood, has examined the relationship among plants in the genus Medicago, beneficial bacteria that dwell in their roots, and parasitic nematodes that try to steal the plants’ nutrients.

The Center for Undergraduate Research & Fellowships provides students in the PURM program awards of $4,500 during the 10-week summer research internship. Wu and Meng stayed busy through those weeks. Whether evaluating plants in a soybean field in Michigan or tending to hundreds—even thousands—of plants in the greenhouse at Penn, these aspiring researchers built a foundation for future scientific endeavors with hands-on practice.

“It’s been an amazing experience,” says Wu. “I’ve always been interested in genetics and evolution and have found parasitic relationships in particular really interesting. I like reading about weird parasites. This summer I’ve gotten to participate in lab meetings, read books about coevolution, and expand my knowledge about the topic.”

Mentored by Ph.D. student McCall Calvert, Wu spent the summer focused on the parasites in the Medicago model system the Wood lab uses. “I’m trying to see if those nematodes are specialists or generalists, if they’re locally adapted to their host plant or open to parasitizing on different species,” Wu says.

To do so, she’s grown pots and pots of plants in the Penn greenhouse, experimentally infecting Medicago plants as well as other species, such as carrot and daisy plants, with nematodes, to measure the degree to which the parasites flourish.

Meng, who is pursuing a bioengineering major, is examining how bacteria that dwell in plant roots affect the plants’ susceptibility to parasites.

Meng’s project looked at the bacterial side of the coevolutionary relationship. Overseen by lab manager and technician Eunnuri Yi, Meng looked at four strains of bacteria, known as rhizobia. Two strains are nitrogen-fixing, giving their associated plants a crucial nutrient to promote growth, while the other two do not seem to contribute nitrogen to the plants, and instead exist as parasites in the plants’ roots. “I’m looking at what happens when we infect the plants with nematode parasites,” Meng says, “to see if the plants that are open to mutualistic rhizobia are more susceptible to the nematode parasites.”

Read the full story in Penn Today.

Linda Wu is a sophomore pursuing an uncoordinated dual degree in business, energy, environment, and sustainability in the Wharton School and in biology with a concentration in ecology and evolution in the College of Arts and Sciences at the University of Pennsylvania.

Nova Meng is a sophomore majoring in bioengineering in the School of Engineering and Applied Science at Penn.