BE Seminar: “Phage and Robotics-Assisted Biomolecular Evolution” (Emma Chory)

Emma Chory, Ph.D.

Speaker: Emma Chory, Ph.D.
Postdoctoral Fellow
Sculpting Evolution Laboratory
Massachusetts Institute of Technology

Date: Thursday, October 21, 2021
Time: 3:30-4:30 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu
Room: Moore 216

Abstract: Evolution occurs when selective pressures from the environment shape inherited variation over time. Within the laboratory, evolution is commonly used to engineer proteins and RNA, but experimental constraints have limited our ability to reproducibly and reliably explore key factors such as population diversity, the timing of environmental changes, and chance. We developed a high-throughput system for the analytical exploration of molecular evolution using phage-based mutagenesis to evolve many distinct classes of biomolecules simultaneously. In this talk, I will describe the development of our open-source python:robot integration platform which enables us to adjust the stringency of selection in response to real-time evolving activity measurements and to dissect the historical, environmental, and random factors governing biomolecular evolution. Finally, I will talk about our many on-going projects which utilize this system to evolve previously intractable biomolecules using novel small-molecule substrates to target the undruggable proteome.

Emma Chory Bio: Emma Chory is a postdoctoral fellow in the Sculpting Evolution Group at MIT, advised by Kevin Esvelt and Jim Collins. Emma’s research utilizes directed evolution, robotics, and chemical biology to evolve biosynthetic pathways for the synthesis of novel peptide-based therapeutics. Emma obtained her PhD in Chemical Engineering in the laboratory of Gerald Crabtree at Stanford University. She is the recipient of the NSF Graduate Research Fellowship and a pre- and postdoctoral NIH NRSA Fellowship.

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.

BE Seminar: “Material Design for Lymph Node Drug Delivery and Immunomodulation” (Susan Thomas)

Susan Thomas, Ph.D.

Speaker: Susan N. Thomas, Ph.D.
Woodruff Associate Professor of Mechanical Engineering
Parker H. Petit Institute of Bioengineering and Bioscience
Georgia Institute of Technology

Date: Thursday, September 23, 2021
Time: 3:30-4:30 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu
This virtual seminar will be held over Zoom. Students registered for BE 699 can gather to watch live in Moore 216, 200 S. 33rd Street.

Abstract: Lymph nodes mediate the co-mingling of cells of the adaptive system to coordinate adaptive immune response. Drug delivery principles and technologies our group has developed to leverage the potential of lymph nodes as immunotherapeutic drug targets to augment anti-cancer therapeutic effects will be described.

Susan Thomas Bio: Susan Napier Thomas is a Woodruff Associate Professor with tenure of Mechanical Engineering in the Parker H. Petit Institute of Bioengineering and Bioscience at the Georgia Institute of Technology where she holds adjunct appointments in Biomedical Engineering and Biological Science and is a member of the Winship Cancer Institute of Emory University. Prior to this appointment, she was a Whitaker postdoctoral scholar at École Polytechnique Fédérale de Lausanne and received her B.S. in Chemical Engineering cum laude from the University of California Los Angeles and her Ph.D. as in Chemical & Biomolecular Engineering as an NSF Graduate Research Fellow from The Johns Hopkins University. For her contributions to the emerging field of immunoengineering, she has been honored with the 2018 Young Investigator Award from the Society for Biomaterials for “outstanding achievements in the field of biomaterials research” and the 2013 Rita Schaffer Young Investigator Award from the Biomedical Engineering Society “in recognition of high level of originality and ingenuity in a scientific work in biomedical engineering.” Her interdisciplinary research program is supported by multiple awards from the National Cancer Institute, the Department of Defense, the National Science Foundation, and the Susan G. Komen Foundation, amongst others.

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.

Penn Engineers Will Use NSF Grant to Develop ‘DReAM’ for On-demand, On-site mRNA Manufacturing

by Melissa Pappas

Daeyeon Lee, Kathleen Stebe and Michael Mitchell

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.

Read the full story in Penn Engineering Today.

BE Seminar: “Synthetic Biochemistry: Engineering Molecules and Pathways for Precision Medicine” (Michael Lin)

Save the date for the first Penn Bioengineering seminar of the fall 2021 semester! This year’s seminars will be hybrids, held virtually on zoom and live on campus!

Michael Lin, Ph.D.

Speaker: Michael Lin, Ph.D.
Associate Professor
Neurobiology, Bioengineering, and by courtesy Chemical and Systems Biology
Stanford Medicine, Stanford University

Date: Thursday, September 2, 2021
Time: 3:30-4:30 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu
Location: Moore Room 216, 200 S. 33rd Street

Abstract: The most effective medicines are those that target the earliest causes of disease, rather than later manifestations. Engineering of biomolecules is a promising but underexplored approach to precisely detecting or targeting disease causes. I will present our work to develop a novel approach to treating cancer by detecting the signaling abnormalities that give rise to cancer. Interestingly, this effort involves biomolecular engineering at multiple scales: proteins, pathways, and viruses. I will also discuss how our work has translated serenditously to developing treatments for SARSCoV2.

Michael Lin Bio: Michael Z. Lin received an A.B. summa cum laude in Biochemistry from Harvard, an M.D. from UCLA, and a Ph.D. from Harvard Medical School. After training in biochemistry and neurobiology as a PhD student with Michael Greenberg at Harvard Medical School, Dr. Lin performed postdoctoral research in fluorescent protein engineering with Chemistry Nobel Laureate Roger Y. Tsien at UCSD. Dr. Lin is a recipient of a Burroughs Wellcome Career Award for Medical Scientists, a Rita Allen Scholar Award, a Damon Runyon-Rachleff Innovation Award, and a NIH Pioneer Award.

Annenberg and Penn Bioengineering Research into Communication Citation Bias

Photo Credit: Debby Hudson / Unsplash

Women are frequently under-cited in academia, and the field of communication is no exception, according to research from the Annenberg School for Communication. The study, entitled “Gendered Citation Practices in the Field of Communication,” was published in Annals of the International Communication Association.

A new study from the Addiction, Health, & Adolescence (AHA!) Lab at the Annenberg School for Communication at the University of Pennsylvania found that men are over-cited and women are under-cited in the field of Communication. The researchers’ findings indicate that this problem is most persistent in papers authored by men.

“Despite known limitations in their use as proxies for research quality, we often turn to citations as a way to measure the impact of someone’s research,” says Professor David Lydon-Staley, “so it matters for individual researchers if one group is being consistently under-cited relative to another group. But it also matters for the field in the sense that if people are not citing women as much as men, then we’re building the field on the work of men and not the work of women. Our field should be representative of all of the excellent research that is being undertaken, and not just that of one group.”

The AHA! Lab is led by David Lydon-Staley, Assistant Professor of Communication and former postdoc in the Complex Systems lab of Danielle Bassett, J. Peter Skirkanich Professor in Bioengineering and in Electrical and Systems Engineering in the School of Engineering and Applied Science. Dr. Bassett and Bassett Lab members Dale Zhou and Jennifer Stiso, graduate students in the Perelman School of Medicine, also contributed to the study.

Read “Women are Under-cited and Men are Over-cited in Communication” in Annenberg School for Communication News.

Jenny Jiang Receives Immunotherapy Grant from Cancer Research Institute

Jenny Jiang, Ph.D.

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.

Decoding How the Brain Accurately Depicts Ever-changing Visual Landscapes

A collaborative study finds that deeper regions of the brain encode visual information more slowly, enabling the brain to identify fast-moving objects and images more accurately and persistently.

by Erica K. Brockmeier

Busy pedestrian crossing at Hong Kong

New research from the University of Pennsylvania, the Scuola Internazionale Superiore de Studi Avanzati (SISSA), and KU Leuven details the time scales of visual information processing across different regions of the brain. Using state-of-the-art experimental and analytical techniques, the researchers found that deeper regions of the brain encode visual information slowly and persistently, which provides a mechanism for explaining how the brain accurately identifies fast-moving objects and images. The findings were published in Nature Communications.

Understanding how the brain works is a major research challenge, with many theories and models developed to explain how complex information is processed and represented. One area of particular interest is vision, a major component of neural activity. In humans, for example, there is evidence that around half of the neurons in the cortex are related to vision.

Researchers are eager to understand how the visual cortex can process and retain information about objects in motion in a way that allows people to take in dynamic scenes while still retaining information about and recognizing the objects around them.

“One of the biggest challenges of all the sensory systems is to maintain a consistent representation of our surroundings, despite the constant changes taking place around us. The same holds true for the visual system,” says Davide Zoccolan, director of SISSA’s Visual Neuroscience Laboratory. “Just look around us: objects, animals, people, all on the move. We ourselves are moving. This triggers rapid fluctuations in the signals acquired by the retina, and until now it was unclear whether the same type of variations apply to the deeper layers of the visual cortex, where information is integrated and processed. If this was the case, we would live in tremendous confusion.”

Experiments using static stimuli, such as photographs, have found that information from the sensory periphery are processed in the visual cortex according to a finely tuned hierarchy. Deeper regions of the brain then translate this information about visual scenes into more complex shapes, objects, and concepts. But how this process works in more dynamic, real-world settings is not well understood.

To shed light on this, the researchers analyzed neural activity patterns in multiple visual cortical areas in rodents while they were being shown dynamic visual stimuli. “We used three distinct datasets: one from SISSA, one from a group in KU Leuven led by Hans Op de Beeck and one from the Allen Institute for Brain Science in Seattle,” says Zoccolan. “The visual stimuli used in each were of different types. In SISSA, we created dedicated video clips showing objects moving at different speeds. The other datasets were acquired using various kinds of clips, including from films.”

Next, the researchers analyzed the signals registered in different areas of the visual cortex through a combination of sophisticated algorithms and models developed by Penn’s Eugenio Pasini and Vijay Balasubramanian. To do this, the researchers developed a theoretical framework to help connect the images in the movies to the activity of specific neurons in order to determine how neural signals evolve over different time scales.

“The art in this science was figuring out an analysis method to show that the processing of visual images is getting slower as you go deeper and deeper in the brain,” says Balasubramanian. “Different levels of the brain process information over different time scales; some things could be more stable, some quicker. It’s very hard to tell if the time scales across the brain are changing, so our contribution was to devise a method for doing this.”

Read the full story in Penn Today.

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