Tag: Penn Engineering

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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Accelerating CAR T Cell Therapy: Lipid Nanoparticles Speed Up Manufacturing

by Ian Scheffler

Visualization of a CAR T cell (in red) attacking a cancer cell (in blue) (Meletios Varras via Getty Images)

For patients with certain types of cancer, CAR T cell therapy has been nothing short of life changing. Developed in part by Carl June, Richard W. Vague Professor at Penn Medicine, and approved by the Food and Drug Administration (FDA) in 2017, CAR T cell therapy mobilizes patients’ own immune systems to fight lymphoma and leukemia, among other cancers.

However, the process for manufacturing CAR T cells themselves is time-consuming and costly, requiring multiple steps across days. The state of the art involves extracting patients’ T cells, then activating them with tiny magnetic beads, before giving the T cells genetic instructions to make chimeric antigen receptors (CARs), the specialized receptors that help T cells eliminate cancer cells.

Now, Penn Engineers have developed a novel method for manufacturing CAR T cells, one that takes just 24 hours and requires only one step, thanks to the use of lipid nanoparticles (LNPs), the potent delivery vehicles that played a critical role in the Moderna and Pfizer-BioNTech COVID-19 vaccines.

In a new paper in Advanced Materials, Michael J. Mitchell, Associate Professor in Bioengineering, describes the creation of “activating lipid nanoparticles” (aLNPs), which can activate T cells and deliver the genetic instructions for CARs in a single step, greatly simplifying  the CAR T cell manufacturing process. “We wanted to combine these two extremely promising areas of research,” says Ann Metzloff, a doctoral student in Bioengineering and NSF Graduate Research Fellow in the Mitchell lab and the paper’s lead author. “How could we apply lipid nanoparticles to CAR T cell therapy?”

Read the full story in Penn Engineering Today.

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

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

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

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

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

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

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

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

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

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

Read more stories featuring Sonura in the BE Blog.

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Penn Bioengineering Student Kaitlin Mrksich Named 2024 Goldwater Scholar

by Louisa Shepard

Four University of Pennsylvania undergraduates have received 2024 Goldwater Scholarships, awarded to second- or third-year students planning research careers in mathematics, the natural sciences, or engineering.

Penn’s 2024 Goldwater Scholars are third-years Hayle Kim, Eric Myzelev, and Eric Tao in the College of Arts and Sciences, and Kaitlin Mrksich in the School of Engineering and Applied Science.

They are among the 438 students named 2024 Goldwater Scholars from 1,353 undergraduates students nominated by 446 academic institutions in the United States, according to the Barry Goldwater Scholarship & Excellence in Education Foundation. Each scholarship provides as much as $7,500 each year for as many as two years of undergraduate study.

The students applied for the Goldwater Scholarship with assistance from Penn’s Center for Undergraduate Research and Fellowships. Penn has had 63 Goldwater Scholars named since Congress established the scholarship in 1986 to honor U.S. Senator Barry Goldwater.

Mrksich, from Hinsdale, Illinois, is majoring in bioengineering. She is interested in developing drug delivery systems that can serve as novel therapeutics for a variety of diseases. Mrksich works in the lab of Michael J. Mitchell where she investigates the ionizable lipid component of lipid nanoparticles for mRNA delivery. At Penn, Mrksich is the president of the Biomedical Engineering Society, where she plans community building and professional development events for bioengineering majors. She is a member of the Kite and Key Society, where she organizes virtual programming to introduce prospective students to Penn. She is a member of Tau Beta Pi engineering honor society, and the Sigma Kappa sorority. She also teaches chemistry to high schoolers as a volunteer in the West Philadelphia Tutoring Project through the Civic House. After graduating, Mrksich plans to pursue an M.D./Ph.D. in bioengineering.

Read the full announcement in Penn Today.

Mrksich was awarded a Student Award for Outstanding Research (Undergraduate) by the Society for Biomaterials earlier this year. Read the story in the BE Blog.

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A Moonshot for Obesity: New Molecules, Inspired by Space Shuttles, Advance Lipid Nanoparticle Delivery for Weight Control

by Ian Scheffler

Like space shuttles using booster rockets to breach the atmosphere, lipid nanoparticles (LNPs) equipped with the new molecule more successfully deliver medicinal payloads. (Love Employee via Getty Images)

Inspired by the design of space shuttles, Penn Engineering researchers have invented a new way to synthesize a key component of lipid nanoparticles (LNPs), the revolutionary delivery vehicle for mRNA treatments including the Pfizer-BioNTech and Moderna COVID-19 vaccines, simplifying the manufacture of LNPs while boosting their efficacy at delivering mRNA to cells for medicinal purposes.

In a paper in Nature Communications, Michael J. Mitchell, Associate Professor in the Department of Bioengineering, describes a new way to synthesize ionizable lipidoids, key chemical components of LNPs that help protect and deliver medicinal payloads. For this paper, Mitchell and his co-authors tested delivery of an mRNA drug for treating obesity and gene-editing tools for treating genetic disease. 

Previous experiments have shown that lipidoids with branched tails perform better at delivering mRNA to cells, but the methods for creating these molecules are time- and cost-intensive. “We offer a novel construction strategy for rapid and cost-efficient synthesis of these lipidoids,” says Xuexiang Han, a postdoctoral student in the Mitchell Lab and the paper’s co-first author. 

Read the full story in Penn Engineering Today.

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Beyond Bias: The Annual Women in Data Science Conference Unites Women across Penn

by Ian Scheffler

Lasya Sreepada, a doctoral student in Bioengineering (BE), addresses the crowd. (Image: Lamont Abrams)

In Invisible Women: Data Bias in a World Designed for Men, Caroline Criado Perez notes that the default perspective for virtually all data collection and analysis is male. (Hence crash test dummies being designed to mimic male bodies, air conditioning systems relying on a model of the male metabolism, and women’s unique heart attack symptoms other than chest pain — like nausea and back pain — often going unrecognized, even by women experiencing them.)

Nearly a decade ago, a group of women at Stanford decided to address this issue by convening a one-day technical conference on data science; that meeting has now grown into a worldwide movement, with hundreds of sister conferences each year — a tradition in which Penn Engineering is proud to take part.

By 2030, Women in Data Science (WiDS), the non-profit that spun out of that early meeting, hopes to achieve 30% representation of women in data science globally. For Susan Davidson, Weiss Professor in Computer and Information Science (CIS) and a co-chair of the annual WiDS @ Penn conference, the benefits of participating in WiDS go beyond just networking. “To see women who are successful in your field is extremely encouraging,” says Davidson.

This year, Penn Engineering partnered with Analytics at Wharton (AAW) and the Penn Museum to co-host the fifth annual WiDS @ Penn conference, bringing together dozens of women from across the University and beyond to learn about the latest applications of data science in topics as diverse as online education and health care.

“It gave me the opportunity to not only show others what it means to be a data scientist,” says Lasya Sreepada, a doctoral student in Bioengineering, who presented her work studying early-onset Alzheimer’s disease using large data sets, “but also what it means to be a woman applying data science to integrate multiple disciplines spanning neuroscience, genomics and radiology.”

Penn Engineering students from all levels of their academic careers participated, from Aashika Vishwanath, a sophomore in CIS, president of the Wharton Undergraduate Data Analytics Club and senior data science consultant at Wharton Analytics Fellows, who shared her work developing an AI-powered teaching assistant, to Betty Xu, a master’s student in Electrical and Systems Engineering, who collaborated with the Wharton Neuroscience Initiative to study financial decision making. “Data can help us know the unknown in every field,” says Xu. “You can be a great data scientist no matter your background.”

Read the full story in Penn Engineering Today.

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Penn Bioengineering Celebrates the Art in Engineering

To commemorate the 50th anniversary of the Department of Bioengineering at the University of Pennsylvania, the department has acquired several pieces of artwork that celebrate the beauty of biological forms. The pieces were curated by Nicole Lampl, Director/Curator of the Reeves House Visual Arts Center.

Read a message from Department Chair Dr. Ravi Radhakrishnan: “Penn Bioengineering: The Past, Present and Future“

Vertex (2019)

Artist: Betty Busby

Fiber, 66″ W x 56″ H

Created with a limited palette on artist dyed silk and hemp, Vertex makes a strong impression of motion in the branching imagery derived from fractals.

“I went to the fractal show at the New Mexico Museum of Natural History & Science’s planetarium, and it blew my mind,” says Busby. “They go from a picture of the galaxy down to a picture of an atom, and you see the same image repeated again and again.” The artist’s focus on macro imagery is the product of her lifelong fascination with molecular biology. Constantly exploring new materials and techniques from around the world, Busby has purchased batiks from Bali, dupioni from India, and silk from China that she paints and dyes with acid. The artist sees the variety of materials that she used in her mixed media works as a direct reflection of the incredible diversity found among living things.

About Betty Busby: After graduating from the Rhode Island School of Design with a BFA in ceramics, Betty Busby founded a custom ceramic tile manufacturing firm in Los Angeles. After nearly 20 years of running the firm, she sold the business in 1994 (it is still in operation to this day). Upon relocating to New Mexico, she changed the focus of her artwork to fiber, taking it full time in 2004. Her manufacturing background has lead to constant experimentation with new materials and techniques that fuel her work. Originally inspired by Amish quilts at the Kutztown County Fair near her childhood home in Pennsylvania, her work has made the journey from bed quilts to mixed media sculpture, and is constantly evolving and heading in new directions.

Artist Statement: Betty Busby creates fiber art using technological innovations and unconventional materials to create work with inviting textures. She is often inspired by the macro world, exploring the structures and forms of nature. She uses these images as jumping off points to create abstractions, which become ground-breaking works of art. Betty Busby creates fiber art using technological innovations and unconventional materials to create work with inviting texture. But the voice of textile roots is strong with traditional fabric, paints and dyes, needle and thread and her trusty Singer working alongside her iPad and spun bonded nonwoven fibers.

Pseudomonas Aeruginosa Colony Biofilm (2023)

Artist: Scott Chimileski

Photography mounted on board, 24″ W x 16″ H

The most harmful species of microbes build biofilms and swarm together. When the conditions are right, the Pseudomonas Aeruginosa (pictured here), can shift from a harmless bacterium found in many environments to a pathogen that causes infection in burn wounds.

About Scott Chimileski: Scott Chimileski a microbiologist, imaging specialist, and educator based in Woods Hole, MA, where he is a Research Scientist at the Marine Biological Laboratory (MBL). From 2015 to 2019, he was a postdoctoral fellow in the Kolter Lab within the Department of Microbiology at Harvard Medical School. During that time, Roberto Kolter and Chimileski curated the exhibition Microbial Life: A Universe at the Edge of Sight, open at the Harvard Museum of Natural History from February 2018 through March 2022. They also coauthored Life at the Edge of Sight: A Photographic Exploration of the Microbial World, published by Harvard University Press in 2017. Chimileski’s imagery has been published or broadcast by media outlets including National Geographic, WIRED, TIME, The Atlantic, STAT, Fast Company, NPR, The Scientist, Scientific American, Smithsonian Magazine, The Biologist, HHMI Biointeractive, Tangled Bank Studios, Quanta Magazine, the NIH Director’s Blog, WBUR Boston, The Verge, TED Talks, and CBS Sunday Morning. Exhibitions at public venues across the United States, and in Uruguay, Brazil, Colombia, Scotland, the UK, and Denmark have featured his imagery and scientific interpretation. Chimileski received a Passion in Science Award in Arts & Creativity from New England Biolabs in 2016, and FASEB BioArt awards in 2016, 2017, and 2019.

Artist Statement: Chimileski’s original scientific photography specializes in high resolution macrophotography and time lapse imaging of microbial colonies and behaviors. This collection includes photos captured at sites around the world where exceptional natural microbial forms flourish, such as Yellowstone National Park. Most bacterial and archaeal cells are far too small to see with the naked eye. However, microbes are seldom if ever found in isolation. Rather, the biology of the microbial world is underpinned by the tremendous interactivity, sociality and modularity of individual cells, which often coalesce in great numbers to produce macroscopically visible structures, including biofilms, microbial mats, colonies, swarms and fruiting bodies. Chimileski is focused on the development of macroscopic imaging techniques as well as time-lapse photography and three-dimensional scanning technologies as applied to microbial multicellular forms, collective behaviors, communities and interspecies interactions. He is also interested in leveraging the power of photography as a medium for communicating microbiology to other scientists and to the general public.

Amoeba Hex Pod (2018), Amoeba (2013) and Amoeba Coffin (2013)

Artist: Melissa Bolger

Gouache, ink, and graphite on clayboard, 6″ W x 6″ H x 2″ D

Bolger explores Synthetic Biology and the myriad ways in which it can imbue engineered organisms with new abilities. Redesigned and entirely imagined cellular structures coexist and intermingle as the artist investigates an unseen universe. Through her visual exploration of this scientific field, the artist invites us to ponder what the consequences of replicating nature on a cellular level might have on human evolution.

About Melissa Bolger: Melissa Bolger is a California native and was raised outside of Redding, CA where her parents settled on a remote piece of property, built a house, and raised their family off the grid. her mother sewed the family’s clothes and other household items. For Bolger, the woods were her playground and she grew up hiking, fishing, hunting, riding horses and panning for gold. Some of her early artistic influences grew from those days, living off a dirt road overlooking a canyon and creek, when do-it-yourself was the only way to get things done. Today, she merges the techniques of craft with fine art in her interpretative portraits, recycled materials, paintings and drawings. Melissa Bolger’s work has been exhibited in solo and group shows and her work has been reviewed in publications.

Artist Statement: The “Soft Machines” series explores themes of patterns within nature through the intricate application of pen and ink, gouache, and graphite. Her interest is on cellular structures that are manipulated by synthetic and artificial life. Borrowing from nature and science, microscopic shapes and images are drawn and high-key colors painted that float, hover, and drip in visual metaphors that insinuate synthetic manipulation. Patterns of nature are complex on a nanoscale and certain thoughts arise. What would be the consequences of science’s attempt to replicate nature on a cellular level? How far will synthetic operations continue in human history? What effects will they have on evolution? The manipulation of nature at the nanoscopic level is overwhelming, mind-blowing and psychedelic. While this manipulation has the potential to alter human life in numerous uncharted ways the question of how and what form life will survive in a synthetic and artificial way is mysterious, puzzling and hi-tech. Approaching these themes with curiosity and instinct, exploring and documenting the natural and the unnatural together and maintaining a sense of wonderment is the embodiment of “Soft Machines.” Examining the intricacies of the invisible world give birth to patterns that move like a heartbeat, live and survive against all odds. “Soft Machines” is the beginning of a series of work exploring, investigating and examining particular themes around astrobiology, synthetic cellular and molecular reconstruction. Bolger continues to explore themes of patterns within nature on a nanoscopic scale in her intricate application of pen and ink, gouache, graphite and mixed media. The invisible world under a microscope is a fascinating phenomenon that Bolger uses as a stepping point into inner realms of space that move, float, and drip. Whether it be an alien landscape or intricate organic patterns, the diversity of life on the planet is an essential force and fascination within the work.

Links:

Betty Busby:
Website: bbusbyarts.com
Instagram: @bbusbyarts

Scott Chimileski:
Website: scottchimileskiphotography.com/
Instagram: @socialmicrobes

Melissa Bolger:
Website: melissalouisebolger.com
Instagram: @melissalouisebolger

Nicole Lampl
Website: nicolelampl.crevado.com
Instagram: @thecuriouscurator_nicole
Email: njlampl@gmail.com
Phone: 504-428-8589

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“Switchable” Bispecific Antibodies Pave Way for Safer Cancer Treatment

by Nathi Magubane

Bispecific T cell engagers are emerging as a powerful class of immunotherapy to treat cancer but are sometimes hindered by unwanted outcomes, such as on-target, off-tumor toxicity; cytokine release syndrome; and neurotoxicity. Now, researchers Penn researchers have developed a novel “switchable” bispecific T cell engager that mitigates these negative effects by co-opting a drug already approved by the FDA. (Image: iStock / CIPhotos)

In the ever-evolving battle against cancer, immunotherapy presents a turning point. It began with harnessing the body’s immune system to fight cancer, a concept rooted more than a century ago but only gaining significant momentum in recent years. Pioneering this shift were therapies like CAR T cell therapy, which reprograms a patient’s T cells to attack cancer cells. Within this domain, bispecific T cell engagers, or bispecific antibodies, have emerged as effective treatments for many blood-borne cancers in the clinic and are being evaluated for solid tumor therapy.

These antibodies simultaneously latch onto both a cancer cell and a T cell, effectively bridging the gap between the two. This proximity triggers the T cells to unleash their lethal arsenal, thereby killing the cancer cells. However, bispecific T cell engagers, like many cancer therapies, face hurdles such as cell-specific targeting limitations, known as on-target off-tumor toxicity, which means the tumor is correctly targeted but so are other healthy cells in the body, leading to healthy tissue damage. Moreover, bispecific antibodies may also lead to immune system overactivation, a precursor for cytokine release syndrome (CRS), and neurotoxicity.

Now, researchers led by Michael Mitchell of the University of Pennsylvania have found a way to circumvent many of these deleterious effects by developing a bispecific T cell nanoengager that is equipped with an “off switch.” Their findings are published in Nature Biomedical Engineering.

“We’re excited to show that bispecific antibodies can be tweaked in a way that allows us to tap into their powerful cancer-killing potential without inducing toxicity to healthy tissues,” says Mitchell, associate professor of bioengineering at Penn’s School of Engineering and Applied Science. “This new controllable drug-delivery mechanism, which we call switchable bispecific T cell nanoengagers, or SiTEs, adds this switchable component to the antibody via administering an FDA-approved small-molecule drug, amantadine.”

Read the full story in Penn Today.

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Jenny Jiang Wins CZI Grant to Investigate the Potential Trigger for Neurodegenerative Diseases

Jenny Jiang, Ph.D.

TDP-43 may be one of the most dangerous proteins in the human body, implicated in neurodegenerative conditions like ALS and Alzheimer’s disease. But the protein remains mysterious: how TDP-43 interacts with the immune system, for instance, is still unclear. 

Now, Ning Jenny Jiang, J. Peter and Geri Skirkanich Associate Professor of Innovation in Bioengineering, has been selected for the Collaborative Pairs Pilot Project Awards, sponsored by the Chan Zuckerberg Initiative (CZI), to investigate the relationship between TDP-43 and the immune system. 

Launched in 2018, the Collaborative Pairs Pilot Project Awards support pairs of investigators to explore “innovative, interdisciplinary approaches to address critical challenges in the fields of neurodegenerative disease and fundamental neuroscience.” Professor Jiang will partner with Pietro Fratta, MRC Senior Clinical Fellow and MNDA Lady Edith Wolfson Fellow at the University College London Queen Square Institute of Neurology.

The TDP-43 protein is associated with neurodegenerative diseases affecting the central nervous system, including ALS and Alzehimer’s disease. While the loss of neurons and muscle degeneration cause the progressive symptoms, the diseases themselves may be a previously unidentified trigger for abnormal immune system activity. 

One possible link is the intracellular mislocalization of TDP-43 (known as TDP-43 proteinopathy), when the protein winds up in the wrong location, which the Jiang and Fratta Labs will investigate. Successfully proving this link could result in potentially game-changing new therapies for these neurodegenerative diseases. 

The Jiang Lab at Penn Engineering specializes in systems immunology, using high-throughput sequencing and single-cell and quantitative analysis to understand how the immune system develops and ages, as well as the molecular signatures of immune related diseases. Jiang joined Penn Bioengineering in 2021. 

Since arriving on campus, Jiang has teamed with the recently formed Penn Anti-Cancer Engineering Center (PACE), which seeks to understand the forces that determine how cancer grows and spreads, and Engineers in the Center for Precision Engineering (CPE4H), which focuses on innovations in diagnostics and delivery in the development of customizable biomaterials and implantable devices for individualized care. 

Jiang was elected a member of the American Institute for Medical and Biological Engineering (AIMBE) College of Fellows in 2021, and has previously won multiple prestigious awards including the NSF CAREER, a Cancer Research Institute Lloyd J. Old STAR Award, and a CZI Neurodegeneration Challenge Network Ben Barres Early Career Acceleration Award.

Jiang is a leader in high-throughput and high-dimensional analysis of T cells, a type of white blood cell crucial to the functioning of a healthy immune system. A recent study in Nature Immunology described the Jiang Lab’s TetTCR-SeqHD technology, the first approach to provide a multifaceted analysis of antigen-specific T cells in a high-throughput manner.

The CZI Collaborative Pairs Pilot Project Awards will provide $200,000 of funding over 18 months with a chance to advance to the second phase of $3.2 million in funding over a four-year period. 

Read the full list of grantees on the CZI’s Neurodegeneration Challenge Network (NDCN) Projects website here.

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Illuminating the Invisible: Bringing the Smallest Protein Clusters into Focus

by Ian Scheffler

The bright white spots represent tiny clusters of proteins detected by CluMPS. (Photo by: Thomas Mumford)

Penn Engineers have pioneered a new way to visualize the smallest protein clusters, skirting the physical limitations of light-powered microscopes and opening new avenues for detecting the proteins implicated in diseases like Alzheimer’s and testing new treatments.

In a paper in Cell Systems, Lukasz Bugaj, Assistant Professor in Bioengineering, describes the creation of CluMPS, or Clusters Magnified by Phase Separation, a molecular tool that activates by forming conspicuous blobs in the presence of target protein clusters as small as just a few nanometers. In essence, CluMPS functions like an on/off switch that responds to the presence of clusters of the protein it is programmed to detect.

Normally, says Bugaj, detecting such clusters requires laborious techniques. “With CluMPS, you don’t need anything beyond the standard lab microscope.” The tool fuses with the target protein to form condensates orders of magnitude larger than the protein clusters themselves that resemble the colorful blobs in a lava lamp. “We think the simplicity of the approach is one of its main benefits,” says Bugaj. “You don’t need specialized skills or equipment to quickly see whether there are small clusters in your cells.”

Read the full story in Penn Engineering Today.