Looking to AI to Solve Antibiotic Resistance

by Nathi Magubane

Cesar de la Fuente (left), Fangping Wan (center), and Marcelo der Torossian Torres (right). Fangping holds a 3D model of a unique ATP synthase fragment, identified by their lab’s deep learning model, APEX, as having potent antibiotic properties.

“Make sure you finish your antibiotics course, even if you start feeling better’ is a medical mantra many hear but ignore,” says Cesar de la Fuente of the University of Pennsylvania.

He explains that this phrase is, however, crucial as noncompliance could hamper the efficacy of a key 20th century discovery, antibiotics. “And in recent decades, this has led to the rise of drug-resistant bacteria, a growing global health crisis causing approximately 4.95 million deaths per year and threatens to make even common infections deadly,” he says.

De la Fuente, a Presidential Assistant Professor, and a team of interdisciplinary researchers have been working on biomedical innovations tackling this looming threat. In a new study, published in Nature Biomedical Engineering, they developed an artificial intelligence tool to mine the vast and largely unexplored biological data—more than 10 million molecules of both modern and extinct organisms— to discover new candidates for antibiotics.

“With traditional methods, it takes around six years to develop new preclinical drug candidates to treat infections and the process is incredibly painstaking and expensive,” de la Fuente says. “Our deep learning approach can dramatically reduce that time, driving down costs as we identified thousands of candidates in just a few hours, and many of them have preclinical potential, as tested in our animal models, signaling a new era in antibiotic discovery.” César de la Fuente holds a 3D model of a unique ATP synthase fragment, identified by his lab’s deep learning model, APEX, as having potent antibiotic properties. This molecular structure, resurrected from ancient genetic data, represents a promising lead in the fight against antibiotic-resistant bacteria.

These latest findings build on methods de la Fuente has been working on since his arrival at Penn in 2019. The team asked a fundamental question: Can machines be used to accelerate antibiotic discovery by mining the world’s biological information? He explains that this idea is based on the notion that biology, at its most basic level, is an information source, which could theoretically be explored with AI to find new useful molecules.

Read the full story in Penn Today.

Artificial Intelligence to Accelerate Antibiotic Discovery

Using AI for discovery of new antibiotics.

The growing threat of antimicrobial resistance demands innovative solutions in drug discovery. Scientists are turning to artificial intelligence (AI) and machine learning (ML) to accelerate the discovery and development of antimicrobial peptides (AMPs). These short strings of amino acids are promising for combating bacterial infections, yet transitioning them into clinical use has been challenging. Leveraging novel AI-driven models, researchers aim to overcome these obstacles, heralding a new era in antimicrobial therapy.

A new article in Nature Reviews Bioengineering illuminates the promises and challenges of using AI for antibiotic discovery. Cesar de la Fuente, Presidential Assistant Professor in Microbiology and Psychiatry in the Perelman School of Medicine, in Bioengineering and Chemical and Biomolecular Engineering in the School of Engineering and Applied Science, and Adjunct Assistant Professor in Chemistry in the School of Arts and Sciences, collaborated with James J. Collins, Termeer Professor of Medical Engineering and Science at MIT, to provide an introduction to this emerging field, outlining both its current limitations and its massive potential.

In the past five years, groundbreaking work in the de la Fuente Lab has dramatically accelerated the discovery of new antibiotics, reducing the timeline from years to mere hours. AI-driven approaches employed in his laboratory have already yielded numerous preclinical candidates, showcasing the transformative potential of AI in antimicrobial research and offering new potential solutions against currently untreatable infections.

Recent advancements in AI and ML are revolutionizing drug discovery by enabling the precise prediction of biomolecular properties and structures. By training ML models on high-quality datasets, researchers can accurately forecast the efficacy, toxicity and other crucial attributes of novel peptides. This predictive power expedites the screening process, identifying promising candidates for further evaluation in a fraction of the time required by conventional methods.

Traditional approaches to AMP development have encountered hurdles such as toxicity and poor stability. AI models help overcome these challenges by designing peptides with enhanced properties, improving stability, efficacy and safety profiles, and fast-tracking the peptides’ clinical application.

While AI-driven drug discovery has made significant strides, challenges remain. The availability of high-quality data is a critical bottleneck, necessitating collaborative efforts to curate comprehensive datasets to train ML models. Furthermore, ensuring the interpretability and transparency of AI-generated results is essential for fostering trust and wider adoption in clinical settings. However, the future is promising, with AI set to revolutionize antimicrobial therapy development and address drug resistance.

Integrating AI and ML into antimicrobial peptide development marks a paradigm shift in drug discovery. By harnessing these cutting-edge technologies, researchers can address longstanding challenges and accelerate the discovery of novel antimicrobial therapies. Continuous innovation in AI-driven approaches is likely to spearhead a new era of precision medicine, augmenting our arsenal against infectious diseases.

Read “Machine learning for antimicrobial peptide identification and design” in Nature Reviews Bioengineering.

The de la Fuente Lab uses use the power of machines to accelerate discoveries in biology and medicine. The lab’s current projects include using AI for antibiotic discovery, molecular de-extinction, reprogramming venom-derived peptides to discover new antibiotics, and developing low-cost diagnostics for bacterial and viral infections. Read more posts featuring de la Fuente’s work in the BE Blog.

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.

Karen Xu Honored with P.E.O. Scholar Award

Karen Xu, a 2024 doctoral graduate in Bioengineering at the University of Pennsylvania, is one of 100 doctoral students in the U. S. and Canada selected to receive a $25,000 Scholar Award from the P.E.O. Sisterhood. 

The P.E.O. Scholar Awards were established in 1991 to provide substantial merit-based awards for women of the United States and Canada who are pursuing a doctoral-level degree at an accredited college or university.  Scholar Awards recipients are a select group of women chosen for their high level of academic achievement and their potential for having a positive impact on society.

The P.E.O., founded January 21, 1869, at Iowa Wesleyan College, Mount Pleasant, Iowa, is a philanthropic educational organization dedicated to supporting higher education for women.  There are approximately 6,000 local chapters in the United States and Canada with nearly a quarter of a million active members.

Xu graduated summa cum laude with a B.S.E. in Biomedical Engineering from Duke University in 2018, after which she joined the M.D.-Ph.D. program at the University of Pennsylvania. She completed her Ph.D. in Bioengineering in spring 2024, funded by an NIH NRSA F30 fellowship, and is set to earn her M.D. in 2026. Under the mentorship of Jason Burdick, Bowman Endowed Professor in Chemical and Biological Engineering at the University of Colorado Boulder and Adjunct Professor in Bioengineering in Penn Engineering, and Robert Mauck, Mary Black Ralston Professor in Orthopaedic Surgery in the Perelman School of Medicine and in Bioengineering in Penn Engineering, her doctoral research has focused on engineering disease models to facilitate therapeutic discoveries. Her doctoral thesis involved the fabrication of hydrogels as tissue mimics to investigate how extracellular environments affect cell behaviors, thereby informing repair of dense connective tissues.

Beyond her research, Xu has taught with the Educational Pipeline Program at the Netter Center and the Perelman School of Medicine, where she hopes to inspire and support the next generation of healthcare workers and scientists.

Penn Bioengineering Junior Named 2024 Udall Scholar

by Louisa Shepard

Third-year undergraduate Joey Wu (Image: Courtesy of the Center for Undergraduate Research and Fellowships)

The University of Pennsylvania’s Joey Wu, a third-year student studying bioengineering and environmental science in the Vagelos Integrated Program in Energy Research (VIPER) program, has been named a 2024 Udall Scholar by the Udall Foundation. VIPER is a dual-degree program in the School of Engineering and Applied Science and School of Arts & Sciences.

Wu is among 55second-year and third-year students selected from 406 candidates nominated by 192colleges and universities nationwide. Scholars are recognized for leadership, public service, and commitment to issues related to the environment or to Native American nations. Each scholar will be awarded as much as $7,000.

A Taiwanese-American undergraduate scientist from Woodbury, Minnesota, Wu is the founder and international director of Waterroots, a nonprofit environmental education project that uses climate storytelling to combat water insecurity in more than 20 countries. Wu is a researcher in Penn Engineering’s McBride Lab, where he works as a plant specialist for a project that promotes environmental stability and sustainable agriculture. He is the deputy director of research for the nonprofit Climate Cardinals, a member of Penn’s Student Advisory Group for the Environment, and the North America representative for the Tunza Eco-Generation Ambassador program. Wu is a Clinton Global Initiative Scholar, a Duke Interfaith Climate Fellow, an IEEE Bio-X Scholar, a 2023 Millennium Fellow, and a 2024 UN ECOSOC Youth Delegate. In addition, he is a resident advisor in Penn’s Stouffer College House, as well as a Penn Engineering and a VIPER student ambassador.

Wu is the 10th student from Penn to be named a Udall Scholar since Congress established the foundation in 1992 to honor Morris and Stewart Udall for their impact on the nation’s environment, public lands, and natural resources and for their support of the rights and self-governance of American Indians and Alaska Natives.

Wu applied to the Udall Scholarship with the support of Penn’s Center for Undergraduate Research and Fellowships.

This story was originally posted in Penn Today.

The CiPD Partners with the Mack Institute for Innovation and Management to Develop Tooth-Brushing Robots

by Melissa Pappas

Left to right: Hong-Huy Tran, Chrissie Jaruchotiratanasakul, Manali Mahajan (Photo Courtesy of CiPD)

The Center for Innovation and Precision Dentistry (CiPD), a collaboration between Penn Engineering and Penn Dental Medicine, has partnered with Wharton’s Mack Institute for Innovation Management on a research project which brings robotics to healthcare. More specifically, this project will explore potential uses of nanorobot technology for oral health care. The interdisciplinary partnership brings together three students from different Penn programs to study the commercialization of a new technology that detects and removes harmful dental plaque.

“Our main goal is to bring together dental medicine and engineering for out-of-the-box solutions to address unresolved problems we face in oral health care,” says Hyun (Michel) Koo, Co-Founding Director of CiPD and Professor of Orthodontics. “We are focused on affordable solutions and truly disruptive technologies, which at the same time are feasible and translatable.”

Read the full story in Penn Engineering Today.

Michel Koo is a member of the Penn Bioengineering Graduate Group. Read more stories featuring Koo in the BE Blog.

To learn more about this interdisciplinary research, please visit CiPD.

This press release has been adapted from the original published by the Mack Institute for Innovation Management.

Arjun Raj Explores Whether Cells Can Learn in 2024 Heilmeier Lecture

Arjun Raj (center) accepts the Heilmeier Award, with Bioengineering Department Chair Ravi Radhakrishnan (left) and Dean Vijay Kumar (right).

Arjun Raj, Professor in Bioengineering at Penn Engineering and in Genetics at the Perelman School of Medicine, has been honored with the 2023-24 George H. Heilmeier Faculty Award for Excellence for “pioneering the development and application of single-cell, cancer-fighting technologies.”

The George H. Heilmeier Faculty Award for Excellence in Research was “established by Penn Engineering for the purpose of recognizing excellence in scholarly activities of the faculty. Named in honor of George H. Heilmeier, it recognizes his extraordinary research career, his leadership in technical innovation and public service, and his loyal and steadfast support of Penn Engineering.”

Dr. Raj delivered his lecture, entitled “Can a Cell Learn?” on April 8, 2024. In this talk, Raj explores whether it is possible for cells to adapt to their environment by learning, thereby overcoming their genetic destiny.

Learn more about, this award, Dr. Raj and his research here. View the lecture recording below.

The Raj Lab for Systems Biology is interested in building a quantitative understanding of cellular function. They develop new tools for quantifying biological processes based on imaging and sequencing and then use those techniques to help us answer questions in molecular and cellular biology. Read more stories featuring Raj 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.

Kyle Vining Earns Hartwell Foundation Award to Study Childhood Leukemia

Kyle Vining, D.D.S., Ph.D.

Kyle Vining, Assistant Professor in Preventive and Restorative Sciences in Penn Dental Medicine and in Materials Science and Engineering in Penn Engineering, has received an Individual Biomedical Research Award from The Hartwell Foundation to explore a novel approach to improving treatment for childhood leukemia. Vining is among ten researchers representing eight institutions selected as a 2023 Hartwell Foundation awardee. Vining is also a member of the Penn Bioengineering Graduate Group.

“The proposed studies lay the foundation to make a major scientific impact in the childhood leukemia field and ultimately improve outcomes for children,” says Vining.

Read the full story at Penn Dental Medicine.

Read more stories featuring Vining in the BE Blog.