Melding AI and RNA: Penn’s $18 Million AIRFoundry to Revolutionize RNA Research

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The NSF AIRFoundry will accelerate RNA research using the power of AI and educate the next generation of RNA researchers. (DesignCells via Getty Images)

In a typical foundry, raw materials like steel and copper are melted down and poured into molds to assume new shapes and functions. The U.S. National Science Foundation Artificial Intelligence-driven RNA Foundry (NSF AIRFoundry), led by the University of Pennsylvania and the University of Puerto Rico and supported by an $18-million, six-year grant, will serve much the same purpose, only instead of smithing metal, the “BioFoundry” will create molecules and nanoparticles.

NSF AIRFoundry is one of five newly created BioFoundries, each of which will have a different focus. Bringing together researchers from Penn Engineering, Penn Medicine’s Institute for RNA Innovation, the University of Puerto Rico–Mayagüez (UPR-M), Drexel University, the Children’s Hospital of Philadelphia (CHOP) and InfiniFluidics, the facility, which will be physically located in West Philadelphia and at UPR-M, will focus on ribonucleic acid (RNA), the tiny molecule essential to genetic expression and protein synthesis that played a key role in the COVID-19 vaccines and saved tens of millions of lives.

The facility will use AI to design, optimize and synthesize RNA and delivery vehicles by augmenting human expertise, enabling rapid iterative experimentation, and providing predictive models and automated workflows to accelerate discovery and innovation.

“With NSF AIRFoundry, we are creating a hub for innovation in RNA technology that will empower scientists to tackle some of the world’s biggest challenges, from health care to environmental sustainability,” says Daeyeon Lee, Russell Pearce and Elizabeth Crimian Heuer Professor in Chemical and Biomolecular Engineering in Penn Engineering and NSF AIRFoundry’s director.

“Our goal is to make cutting-edge RNA research accessible to a broad scientific community beyond the health care sector, accelerating basic research and discoveries that can lead to new treatments, improved crops and more resilient ecosystems,” adds Nobel laureate Drew Weissman, Roberts Family Professor in Vaccine Research in Penn Medicine, Director of the Penn Institute for RNA Innovation and NSF AIRFoundry’s senior associate director.

The facility will catalyze new innovations in the field by leveraging artificial intelligence (AI). AI has already shown great promise in drug discovery, poring over vast amounts of data to find hidden patterns. “By integrating artificial intelligence and advanced manufacturing techniques, the NSF AIRFoundry will revolutionize how we design and produce RNA-based solutions,” says David Issadore, Professor in Bioengineering and in Electrical and Systems Engineering at  Penn Engineering and the facility’s associate director of research coordination.

Read the full story on the Penn AI website.

Brewing Brilliance

by Nathi Magubane & Ian Scheffler

Nader Engheta (left) and Firooz Aflatouni swap ideas over cups of tea.

According to Chinese legend, the first cup of tea was an accident. Shennong, a mythical emperor, boiled a pot of water, only for the wind to add a handful of leaves.

In Penn Engineering’s Department of Electrical and Systems Engineering (ESE), tea leaves likewise result in happy accidents.

Nader Engheta, H. Nedwill Ramsey Professor, regularly joins his colleague Firooz Aflatouni, associate professor and undergraduate chair in ESE, for a cup of tea in the latter’s office. “We talk about academic life,” says Engheta. “We talk about history, politics.” And, of course, science.

Engheta, who won the Benjamin Franklin Medal last year, is known for his groundbreaking contributions to the design of materials that interact with electromagnetic waves at tiny scales with unprecedented functionalities. More than a decade ago, the Department recruited Aflatouni, who specializes in the design of electronic and photonic chips, and Engheta became his mentor. “We come from different angles to the field of optics,” says Engheta.

Over tea, the two brew up new ideas. While perhaps not as directly inspired by teatime as James Watt, who famously experimented with kettles en route to inventing the steam engine, the pair nonetheless finds that ideas rise like the steam from their teacups. “It’s a pleasure to collaborate with Firooz,” says Engheta. “We love to see how we can bring our ideas together.” 

Read the full story in Penn Today.

Nader Engheta is H. Nedwill Ramsey Professor of Electrical and Systems Engineering at Penn Engineering, with secondary appointments in the departments of Bioengineering, Materials Science and Engineering, and Physics and Astronomy in the School of Arts & Sciences. Read more stories featuring Engheta in the BE Blog.

Episode 4 of Innovation & Impact: Exploring AI in Engineering

by Melissa Pappas

Susan Davidson, Cesar de la Fuente, Surbhi Goel and Chris Callison-Burch speak on AI in Engineering in episode 4 of the Innovation & Impact podcast.

With AI technologies finding their way into every industry, important questions must be considered by the research community: How can deep learning help identify new drugs? How can large language models disseminate information? Where and how are researchers using AI in their own work? And, how are humans anticipating and defending against potential harmful consequences of this powerful technology?

In this episode of Innovation & Impact, host Susan Davidson, Weiss Professor in Computer and Information Science (CIS), speaks with three Penn Engineering experts about leveraging AI to advance scientific discovery and methods to protect its users. Panelists include:

Chris Callison-Burch, Associate Professor in CIS, who researches the applications of large language models and AI tools in current and future real-world problems with a keen eye towards safety and ethical use of AI;  

Surbhi Goel, Magerman Term Assistant Professor in CIS, who works at the intersection of theoretical computer science and machine learning. Her focus on developing theoretical foundations for modern machine learning paradigms expands the possibilities of deep learning; and

Cesar de la Fuente, Presidential Assistant Professor in Bioengineering, Psychiatry and Microbiology with a secondary appointment in Chemical and Biomolecular Engineering, who leads research on technology in the medical field, using computers to find antibiotics in extinct organisms and identify pre-clinical candidates to advance drug discovery. 

Each episode of Penn Engineering’s Innovation & Impact podcast shares insight from leading experts at Penn and Penn Engineering on science, technology and medicine. 

Subscribe to the Innovation & Impact podcast on Apple MusicSpotify or your favorite listening platforms or find all the episodes on our Penn Engineering YouTube channel.

This story originally appeared in Penn Engineering Today.

A Return to Jamaica Brings Seven Student-Invented Devices to Help People and Wildlife

by Melissa Pappas

Students test the GaitMate harness and structure as a tool to help recovering patients walk.

Penn students have been building their knowledge and hands-on experience in places all over the world through Penn Global Seminars. Last May, “Robotics and Rehabilitation” brought Penn students back to the tropical island of Jamaica to collaborate with local university students and make an impact on recovery and quality of life for patients in Kingston and beyond. 

Course leaders Camillo Jose (CJ) Taylor, Raymond S. Markowitz President’s Distinguished Professor in Computer and Information Science (CIS), and Michelle J. Johnson, Associate Professor of Physical Medicine and Rehabilitation at the Perelman School of Medicine and Associate Professor in Bioengineering (BE) and Mechanical Engineering and Applied Mechanics (MEAM) at Penn Engineering, brought the first cohort of students to the island in 2019

“CJ and I are both Jamaicans by birth,” says Johnson. “We were both excited to introduce the next generation of engineers to robotics, rehabilitation and the process of culturally sensitive design in a location that we are personally connected to.” 

As they built relationships with colleagues at the University of West Indies, Mona (UWI, Mona) and the University of Technology, Jamaica (UTECH), both Johnson and Taylor worked to tie the goals of the course to the location.

“In the initial iteration of the course, our goal was to focus on the applications of robotics to rehabilitation in a developing country where it is necessary to create solutions that are cost effective and will work in under-resourced settings,” says Taylor. 

Taylor and Johnson wanted to make the course a regular offering, however, due to COVID-related travel restrictions, it wasn’t until last spring that they were able to bring it back. But when they did, they made up for lost time and expanded the scope of the course to include solving health problems for both people and the environment.

“While we started with a focus on people, we realized that the health and quality of life of a community is also impacted by the health of the environment,” says Taylor. “Jamaica has rich terrestrial and marine ecosystems, but those resources need to be monitored and regulated. We ventured into developing robotics tools to make environmental monitoring more effective and cost-friendly.”

One of those student-invented tools was a climate survey drone called “BioScout.” 

“Our aim was to create a drone to monitor the ecosystem and wildlife in Jamaica,” says Rohan Mehta, junior in Systems Science and Engineering. “We wanted to help researchers and rangers who need to monitor wildlife and inspect forest sectors without entering and disturbing territories, but there were no available drones that met all of the following criteria necessary for the specific environment: affordable, modular, water-resistant and easy to repair. So we made our own.”

Another team of students created a smart buoy to reduce overfishing. The buoy was equipped with an alarm that goes off when fishermen get too close to a no-fishing zone.

Five other student teams dove into projects aligned to the original goals of the course. Their devices addressed patients’ decreased mobility due to diabetes, strokes and car accidents. These projects were sponsored by the Sir John Golding Rehabilitation Center.

One of which, the GaitMate, was engineered to help stroke patients who had lost partial muscle control regain their ability to walk.  

“We developed a device that supports a patient’s weight and provides sensory feedback to help correct their form and gait as they walk on a treadmill, ultimately enhancing the recovery process and providing some autonomy to the patient,” says Taehwan Kim, senior in BE. “The device is also relatively cheap and simple, making it an option for a wide variety of physical therapy needs in Jamaica and other countries.”

Read the full story in Penn Engineering Today.

Two Penn Bioengineers Receive NIH Director Award

by Nathi Magubane

Jina Ko (left) and Kevin Johnson (right), both from the School of Engineering and the Perelman School of Medicine with appointments in Bioengineering, have received the National Institute of Health Director’s Award to support their “highly innovative and broadly impactful” research projects through the High-Risk, High-Reward program.

The National Institutes of Health (NIH) has awarded grants to three researchers from the University of Pennsylvania through the NIH Common Fund’s High-Risk, High-Reward Research program. The research of Kevin B. Johnson, Jina Ko, and Sheila Shanmugan will be supported through the program, which funds “highly innovative and broadly impactful” biomedical or behavioral research by exceptionally creative scientists.

The High-Risk, High-Reward Research program catalyzes scientific discovery by supporting highly innovative research proposals that, due to their inherent risk, may struggle in the traditional peer-review process despite their transformative potential. Program applicants are encouraged to think “outside the box” and pursue trail-blazing ideas in any area of research relevant to the NIH’s mission to advance knowledge and enhance health.

Two Penn Bioengineering faculty, Johnson and Ko, are among 85 recipients for 2023.

Johnson, the David L. Cohen University Professor of Pediatrics, is a Penn Integrates Knowledge University Professor who holds appointments in the Department of Computer and Information Science in the School of Engineering and Applied Science and the Department of Biostatistics, Epidemiology, and Informatics in the Perelman School of Medicine. He also holds secondary appointments in Bioengineering, Pediatrics, and in the Annenberg School for Communication. He is widely known for his work with e-prescribing and computer-based documentation and, more recently, work communicating science to lay audiences, which includes a documentary about health-information exchange. Johnson has authored more than 150 publications and was elected to the American College of Medical Informatics, Academic Pediatric Society, National Academy of Medicine, International Association of Health Science Informatics, and American Institute for Medical and Biological Engineering.

Ko is an assistant professor in the Department of Pathology and Laboratory Medicine in the Perelman School of Medicine and Department of Bioengineering in the School of Engineering and Applied Science. She focuses on developing single molecule detection from single extracellular vesicles and multiplexed molecular profiling to better diagnose diseases and monitor treatment efficacy. Ko earned her Ph.D. in bioengineering at Penn in 2018, during which time she developed machine learning-based microchip diagnostics that can detect blood-based biomarkers to diagnose pancreatic cancer and traumatic brain injury. For her postdoctoral training, she worked at the Massachusetts General Hospital and the Wyss Institute at Harvard University as a Schmidt Science Fellow and a NIH K99/R00 award recipient. Ko developed new methods to profile single cells and single extracellular vesicles with high throughput and multiplexing.

Read the full announcement in Penn Today.

View the 2023 Department of Bioengineering Juneteenth Address by Dr. Kevin B. Johnson

Thank you to everyone who attended the 2023 Department of Bioengineering Juneteenth Address. For those who were unable to attend or who may wish to share the opportunity to view the lecture, a recording of Dr. Kevin Johnson’s talk, “A White Neighbor, a Black Surgeon, and a Mormon Computer Scientist Walk into a Bar…” is available below.

Speaker:
Kevin B. Johnson, MD, MS, FAAP, FAMIA, FACMI
David L. Cohen University Professor
Computer and Information Science
Biostatistics, Epidemiology and Informatics
Bioengineering
Annenberg School for Communication
Pediatrics
VP for Applied Informatics (UPHS), University of Pennsylvania

Abstract:
As we recognize Juneteenth, a holiday that brings awareness to what journalist Corey Mitchell calls “…a complex understanding of the nation’s past,” we also need to understand how many of our neighbors, staff, and faculty — even those born in the last 100 years — continue to navigate through the environment that made Juneteenth remarkable. In this talk, Dr. Johnson  shares a bit of his personal story and how this story informs his national service and passion for teaching.

On a Different Wavelength, Nader Engheta Leads a Community in Light

Nader Engheta was puzzled when he got a call from the psychology department about a fish.
In the early 1990s, Engheta, a newly minted associate professor of electrical engineering in Penn’s School of Engineering and Applied Science, was a respected expert in radio wave technologies. But in recent years, his work had been expanding into subjects at once more eccentric and fundamental.

Nader Engheta was puzzled when he got a call from the psychology department about a fish.

In the early 1990s, Engheta, a newly minted associate professor of electrical engineering in Penn’s School of Engineering and Applied Science, was a respected expert in radio wave technologies. But in recent years, his work had been expanding into subjects at once more eccentric and fundamental.

Engheta’s interest in electromagnetic waves was not limited to radio frequencies, as a spate of fresh publications could attest. Some studies investigated a range of wave interactions with a class of matter known as a “chiral media,” materials with molecular configurations that exhibit qualities of left or right “handedness.” Others established practical electromagnetic applications for a bewildering branch of mathematics called “fractional calculus,” an area with the same Newtonian roots as calculus proper but a premise as eyebrow-raising as the suggestion a family might literally include two-and-a-half children.

Electromagnetic waves are organized on a spectrum of wavelengths. On the shorter end of the spectrum are high-energy waves, such as X-rays. In the middle, there is the limited range we see as visible light. And on the longer end are the lower-energy regimes of radio and heat.

Researchers tend to focus on one kind of wave or one section of the spectrum, exploring quirks and functions unique to each. But all waves, electromagnetic or not, share the same characteristics: They consist of a repeating pattern with a certain height (amplitude), rate of vibration (frequency), and distance between peaks (wavelength). These qualities can define a laser beam, a broadcasting voice, a wind-swept lake, or a violin string.

Engheta has never been the kind of scholar to limit the scope of his curiosity to a single field of research. He is interested in waves, and his fascination lies equally in the physics that determine wave behavior and the experimental technologies that push the boundaries of those laws.

So, when Edward Pugh, a mathematical psychologist studying the physiology of visual perception, explained that green sunfish might possess an evolutionary advantage for seeing underwater, Engheta listened.

Soon, the two Penn professors were pouring over microscope images of green sunfish retinas.

Read Devorah Fischler’s full story about Nader Engheta and watch an accompanying video at Penn Today.

Nader Engheta is H. Nedwill Ramsey Professor of Electrical and Systems Engineering at Penn Engineering, with secondary appointments in the departments of Bioengineering, Materials Science and Engineering, and Physics and Astronomy in the School of Arts & Sciences.

2023 Department of Bioengineering Juneteenth Address: “A White Neighbor, a Black Surgeon, and a Mormon Computer Scientist Walk into a Bar…” (Kevin B. Johnson)

Kevin B. Johnson, MD, MS

We hope you will join us for the 2023 Department of Bioengineering Juneteenth Address by Dr. Kevin B. Johnson.

Date: Wednesday, June 14, 2023
Start Time: 11:00 AM ET
Location: Berger Auditorium (Skirkanich Hall basement room 013)

Zoom link
Meeting ID: 925 0325 6013
Passcode: 801060

Following the event, a limited number of box lunches will be available for in-person attendees. If you would like a box lunch, please RSVP here by Monday, June 12 so we can get an accurate headcount.

Speaker: Kevin B. Johnson, MD, MS, FAAP, FAMIA, FACMI
David L. Cohen University Professor
Annenberg School for Communication, Bioengineering, Biostatistics, Epidemiology and Informatics, Computer and Information Science, Pediatrics
VP for Applied Informatics (UPHS), University of Pennsylvania

Title: “A White Neighbor, a Black Surgeon, and a Mormon Computer Scientist Walk into a Bar…”

Abstract: As we recognize Juneteenth, a holiday that brings awareness to what journalist Corey Mitchell calls “…a complex understanding of the nation’s past”, we also need to understand how many of our neighbors, staff, and faculty—even those born in the last 100 years—continue to navigate through the environment that made Juneteenth remarkable. Dr. Johnson will share a bit of his personal story and how this story informs his national service and passion for teaching.

Bio: Dr. Johnson is a leader of medical information technologies to improve patient care and safety. He is well regarded and widely known for pioneering discoveries in clinical informatics, leading to advances in data acquisition, medication management, and information aggregation in medical settings.

He is a board-certified pediatrician who has aligned the powers of medicine, engineering and technology to improve the health of individuals and communities. In work that bridges biomedical informatics, bioengineering and computer science, he has championed the development and implementation of clinical information systems and artificial intelligence to drive medical research. He has encouraged the effective use of technology at the bedside, and he has empowered patients to use new tools that help them to understand how medications and supplements may affect their health. He is interested in using advanced technologies such as smart devices and in developing computer-based documentation systems for the point of care. He also is an emerging champion of the use of digital media to enhance science communication, with a successful feature-length documentary describing health information exchange, a podcast (Informatics in the Round) and most recently, a children’s book series aimed at STEM education featuring scientists underrepresented in healthcare.

Dr. Johnson holds joint appointments in the Department of Computer and Information Science of the School of Engineering and Applied Science, and secondary appointments in Bioengineering and the Annenberg School for Communication. He serves as Vice President for Applied Informatics in the University of Pennsylvania Health System and as a Professor of Pediatrics at the Children’s Hospital of Philadelphia.

Before arriving at Penn, he served as the Cornelius Vanderbilt Professor and Chair of the Department of Biomedical Informatics at the Vanderbilt University School of Medicine, where he had taught since 2002. As Senior Vice President for Health Information Technology at the Vanderbilt University Medical Center, he led the development of clinical systems that enabled doctors to make better treatment and care decisions for individual patients, and introduced new systems to integrate artificial intelligence into patient care workflows.

The author of more than 150 publications, Dr. Johnson has held numerous leadership positions in the American Medical Informatics Association and the American Academy of Pediatrics. He leads the American Board of Pediatrics Informatics Advisory Committee, directs the Board of Scientific Counselors of the National Library of Medicine, and is a member of the NIH Council of Councils. He is an elected member of the National Academy of Medicine, American College of Medical Informatics and Academic Pediatric Society. He has received awards from the Robert Wood Johnson Foundation and American Academy of Pediatrics, among many others.

Folding@Home: How You, and Your Computer, Can Play Scientist

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Greg Bowman kneels, working on a server.
Folding@home is led by Gregory Bowman, a Penn Integrates Knowledge Professor who has appointments in the Departments of Biochemistry and Biophysics in the Perelman School of Medicine and the Department of Bioengineering in the School of Engineering and Applied Science. (Image: Courtesy of Penn Medicine News)

Two heads are better than one. The ethos behind the scientific research project Folding@home is that same idea, multiplied: 50,000 computers are better than one.

Folding@home is a distributed computing project which is used to simulate protein folding, or how protein molecules assemble themselves into 3-D shapes. Research into protein folding allows scientists to better understand how these molecules function or malfunction inside the human body. Often, mutations in proteins influence the progression of many diseases like Alzheimer’s disease, cancer, and even COVID-19.

Penn is home to both the computer brains and human minds behind the Folding@home project which, with its network, forms the largest supercomputer in the world. All of that computing power continually works together to answer scientific questions such as what areas of specific protein implicated in Parkinson’s disease may be susceptible to medication or other treatment.

Led by Gregory Bowman, a Penn Integrates Knowledge professor of Biochemistry and Biophysics in the Perelman School of Medicine who has joint appointments in the Department of Biochemistry and Biophysics in the Perelman School of Medicine and the Department of Bioengineering in the School of Engineering and Applied Science, Folding@home is open for any individual around the world to participate in and essentially volunteer their computer to join a huge network of computers and do research.

Using the network hub at Penn, Bowman and his team assign experiments to each individual computer which communicates with other computers and feeds info back to Philly. To date, the network is comprised of more than 50,000 computers spread across the world.

“What we do is like drawing a map,” said Bowman, explaining how the networked computers work together in a type of system that experts call Markov state models. “Each computer is like a driver visiting different places and reporting back info on those locations so we can get a sense of the landscape.”

Individuals can participate by signing up and then installing software to their standard personal desktop or laptop. Participants can direct the software to run in the background and limit it to a certain percentage of processing power or have the software run only when the computer is idle.

When the software is at work, it’s conducting unique experiments designed and assigned by Bowman and his team back at Penn. Users can play scientist and watch the results of simulations and monitor the data in real time, or they can simply let their computer do the work while they go about their lives.

Read the full story at Penn Medicine News.

Why is Machine Learning Trending in Medical Research but not in Our Doctor’s Offices?

by Melissa Pappas

Illustration of a robot in a white room with medical equipment.Machine learning (ML) programs computers to learn the way we do – through the continual assessment of data and identification of patterns based on past outcomes. ML can quickly pick out trends in big datasets, operate with little to no human interaction and improve its predictions over time. Due to these abilities, it is rapidly finding its way into medical research.

People with breast cancer may soon be diagnosed through ML faster than through a biopsy. Those suffering from depression might be able to predict mood changes through smart phone recordings of daily activities such as the time they wake up and amount of time they spend exercising. ML may also help paralyzed people regain autonomy using prosthetics controlled by patterns identified in brain scan data. ML research promises these and many other possibilities to help people lead healthier lives.

But while the number of ML studies grow, the actual use of it in doctors’ offices has not expanded much past simple functions such as converting voice to text for notetaking.

The limitations lie in medical research’s small sample sizes and unique datasets. This small data makes it hard for machines to identify meaningful patterns. The more data, the more accuracy in ML diagnoses and predictions. For many diagnostic uses, massive numbers of subjects in the thousands would be needed, but most studies use smaller numbers in the dozens of subjects.

But there are ways to find significant results from small datasets if you know how to manipulate the numbers. Running statistical tests over and over again with different subsets of your data can indicate significance in a dataset that in reality may be just random outliers.

This tactic, known as P-hacking or feature hacking in ML, leads to the creation of predictive models that are too limited to be useful in the real world. What looks good on paper doesn’t translate to a doctor’s ability to diagnose or treat us.

These statistical mistakes, oftentimes done unknowingly, can lead to dangerous conclusions.

To help scientists avoid these mistakes and push ML applications forward, Konrad Kording, Nathan Francis Mossell University Professor with appointments in the Departments of Bioengineering and Computer and Information Science in Penn Engineering and the Department of Neuroscience at Penn’s Perelman School of Medicine, is leading an aspect of a large, NIH-funded program known as CENTER – Creating an Educational Nexus for Training in Experimental Rigor. Kording will lead Penn’s cohort by creating the Community for Rigor which will provide open-access resources on conducting sound science. Members of this inclusive scientific community will be able to engage with ML simulations and discussion-based courses.

“The reason for the lack of ML in real-world scenarios is due to statistical misuse rather than the limitations of the tool itself,” says Kording. “If a study publishes a claim that seems too good to be true, it usually is, and many times we can track that back to their use of statistics.”

Such studies that make their way into peer-reviewed journals contribute to misinformation and mistrust in science and are more common than one might expect.

Read the full story in Penn Engineering Today.