César de La Fuente Uses AI to Discover Germ-fighting Peptides

César de la Fuente, PhD

The impending danger of bacterial resistance to antibiotics is well-documented within the scientific community. Bacteria are the most efficient evolvers, and their ability to develop tolerance to drugs, in addition to antibiotic overuse and misuse, means that researchers have had to get particularly resourceful to ensure the future of modern medicine.  

Presidential Assistant Professor in Bioengineering, Microbiology, Psychiatry, and Chemical and Biomolecular Engineering César de la Fuente and his team are using an algorithm to search the human genome for microbe-fighting peptides. So far, the team has synthesized roughly 55 peptides that, when tested against popular drug-resistant microbes such as the germ responsible for staph infections, have proven to prevent bacteria from replicating.  

WIRED’s Max G. Levy recently spoke with de la Fuente and postdoctoral researcher and study collaborator Marcelo Torres about the urgency of the team’s work, and why developing these solutions is critical to the survival of civilization as we know it. The team’s algorithm, based on pattern recognition software used to analyze images, makes an otherwise insurmountable feat tangible.  

De la Fuente’s lab specializes in using AI to discover and design new drugs. Rather than making some all-new peptide molecules that fit the bill, they hypothesized that an algorithm could use machine learning to winnow down the huge repository of natural peptide sequences in the human proteome into a select few candidates.

“We know those patterns—the multiple patterns—that we’re looking for,” says de la Fuente. “So that allows us to use the algorithm as a search function.”

Read Max G. Levy’s An AI Finds Superbug-Killing Potential in Human Proteins” at WIRED. 

This story previously appeared in Penn Engineering Today.

Strella Biotechnology Continues Scaling Up

Katherine Sizov (right) and Malika Shukurova (left) earned the 2019 President’s Innovation Prize for their startup, Strella Biotechnology.

“Fruit hacking” startup Strella Biotechnology, founded by students and faculty advisors from the School of Engineering and Applied Science (SEAS) and the School of Arts and Sciences (SAS), tackles food waste by monitoring fruit ripeness. No stranger to media coverage, Strella and co-founder Katherine Sizov have previously been spotlighted for receiving the 2019 President’s Innovation Prize, which included $100,000 of financial support, a $50,000 living stipend for both awardees, and a year of dedicated co-working and lab space at the Pennovation Center. 

Recently, Michael Birnbaum of the Washington Post spoke with Sizov about the hard work and flexibility it took to propel the company’s successful scaling endeavors: Strella is now monitoring 15 percent of all U.S. apples.  

“Sizov, 24, wants to eliminate food waste one fruit at a time. In central Washington, it was an effort that required almost as much quick footwork as the épée squad she captained as a championship fencer in college. One moment, she was trying to beam the sensor’s WiFi signal through the reception black hole of millions of apples, which cause transmission issues because of their high water content. The next, she was sitting down with laconic apple growers with orchards planted generations ago, trying to convince them she could help them avoid wasted fruit. By day’s end, she might be folding her 6-foot frame into the passenger seat of a rental car, balancing her laptop on her knees and trying to win over Silicon Valley investors on Zoom calls using skills she had picked up partly by watching YouTube tutorials.”

Read Michael Birnbaum’s Fighting food waste, one apple at a time” for more about Sizov’s motivation, background and process.

Strella Biotechnology was founded by Penn alumna Katherine Sizov (Bio 2019) and was initially developed in the George H. Stephenson Foundation Educational Laboratory, the biomakerspace and primary teaching lab of the Department of Bioengineering. Sizov and Penn Bioengineering alumna Malika Shukurova (BSE 2019) won a President’s Innovation Prize in 2019. Read more BE blog stories featuring Strella Biotechnology.

Carl June Highlighted for Success in Gene Therapy

Carl June, MD

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

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

Strella Biotechnology Featured in Philly Mag

NextUp, a regular feature of Philadelphia Magazine that “highlights the local leaders, organizations and research shaping the Greater Philadelphia region’s life sciences ecosystem,” ran a profile of Philly-based agricultural startup Strella Biotechnology. Founded by Penn alumna Katherine Sizov (Bio 2019) and winner of a 2019 President’s Innovation Prize, Strella Biotech seeks to reduce food waste through innovative biosensors, and was initially developed in the George H. Stephenson Foundation Educational Laboratory, the biomakerspace and primary teaching lab of the Department of Bioengineering.

Sizov says the coronavirus pandemic has made the volatility of grocery stores’ offerings even more apparent. Last April, the Produce Marketing Association estimated that nearly $5 billion of fresh fruits and vegetables had gone to waste in the first month of the pandemic due to the complex supply chain’s inability to quickly redirect shipping and distribution. ‘In a way, I think COVID-19 has helped us realize how delicate and fragile supply chains are,’ she says. ‘We are working to create better, stronger supply chains that are economically and environmentally sustainable for everyone involved — researchers, growers, packagers, distributors, retailers, and consumers.'”

Read “NextUp: The Philly Startup Using Biosensors to Combat Food Waste and Improve Supply Chains” in Philly Mag.

Read more BE blog stories featuring Strella Biotechnology.

César de la Fuente Featured in “40 Under 40” List

César de la Fuente, Ph.D.

César de la Fuente, PhD, Presidential Assistant Professor in Bioengineering, Chemical and Biomolecular Engineering, Psychiatry, and Microbiology, was featured in the Philadelphia Business Journal’s Class of 2021 “40 Under 40” list. Currently focused on antibiotic discovery, creating tools for microbiome engineering, and low-cost diagnostics, de le Fuente pioneered the world’s first computer-designed antibiotic with efficacy in animal models.

De la Fuente was previously included in the AIChE’s “35 Under 35” list in 2020 and most recently published his work demonstrating a rapid COVID-19 diagnostic test which delivers highly accurate results within four minutes.

Read “40 Under 40: Philadelphia Business Journal’s complete Class of 2021” here.

Read other BE blog posts featuring Dr. de la Fuente here.

Rapid COVID-19 Diagnostic Test Delivers Results Within 4 Minutes With 90 Percent Accuracy

RAPID, a low-cost COVID-19 diagnostic test, can detect SARS-CoV-2 within four minutes with 90 percent accuracy

Even as COVID-19 vaccinations are being rolled out, testing for active infections remains a critical tool in fighting the pandemic. Existing rapid tests that can directly detect the virus rely on reverse transcription polymerase chain reaction (RT-PCR), a common genetic assay that nevertheless requires trained technicians and lab space to conduct.

Alternative testing methods that can be scaled up and deployed in places where those are in short supply are therefore in high demand.

Penn researchers have now demonstrated such a method, which senses the virus by measuring the change in an electrical signal when a piece of the SARS-CoV-2 virus binds to a biosensor in their device, which they call RAPID 1.0.

The work, published in the journal Matter, was led by César de la Fuente, a Presidential Assistant Professor who has appointments in Engineering’s departments of Chemical and Biomolecular Engineering, and Bioengineering, as well as in Psychiatry and Microbiology in the Perelman School of Medicine.

“Prior to the pandemic, our lab was working on diagnostics for bacterial infections. But then, COVID-19 hit. We felt a responsibility to use our expertise to help—and the diagnostic space was ripe for improvements,” de la Fuente said. “We feel strongly about the health inequities witnessed during the pandemic, with testing access and the vaccine rollout, for example. We believe inexpensive diagnostic tests like RAPID could help bridge some of those gaps.”

The RAPID technology uses electrochemical impedance spectroscopy (EIS), which transforms the binding event between the SARS-CoV-2 viral spike protein and its receptor in the human body, the protein ACE2 (which provides the entry point for the coronavirus to hook into and infect human cells), into an electrical signal that clinicians and technicians can detect. That signal allows the test to discriminate between infected and healthy human samples. The signal can be read through a desktop instrument or a smartphone.

Read more about RAPID at Penn Medicine News.

Originally posted on Penn Engineering Today.

“Science vs Science: The Contradictory Fight Over Whether Electromagnetic Hypersensitivity is Real”

cell phones
Kenneth R. Foster, Ph.D.

Electromagnetic fields are everywhere, and especially so in recent years. To most of us, those fields are undetectable. But a small number of people believe they have an actual allergy to electromagnetic fields. Ken Foster, a Professor Emeritus of Bioengineering, has heard these arguments before.  “Activists would point to all these biological effects studies and say, ‘There must be some hazard’; health agencies would have meticulous reviews of literature and not see much of a problem.”

Listen to the episode of The Pulse and read the full story at WHYY.

Originally posted on Penn Today.

Bioengineering’s Organ-on-a-chip Spin-off is Growing

Andrei Georgescu (left) and Dan Huh are the co-founders of Vivodyne, a spin-off of Huh’s BIOLines lab.

Dan Huh, Associate Professor in the Department of Bioengineering, has been steadily growing a collection of organs-on-chips. These devices incorporate human cells into precisely engineered microfluidic channels that mimic an organ’s natural environment, providing a way to conduct experiments that would not otherwise be feasible.

Huh’s previous research has involved using a placenta-on-a-chip to study which drugs are able to reach a developing fetus; investigating microgravity’s effect on the immune system by sending one of his chips to the International Space Station; and testing treatments for dry eye disease using an eye-on-a-chip, complete with a mechanical blinking eyelid.

Now, he and his colleagues are taking this technology out of their lab and into industry with their company, Vivodyne.

Andrei Georgescu, Huh’s lab-member and co-founder of Vivodyne, recently spoke with Technical.ly Philly’s Paige Gross about the growth of their company.

Research into potential drugs is usually performed first on mice, and success is only found in a fraction of humans once implemented in clinical trials, Andrei Georgescu, cofounder and CEO of Vivodyne, told Technical.ly. The genetic makeup just isn’t similar enough. But technology that allows scientists to test therapies on lab-grown human organs called “organs on chip” is allowing for testing without human subjects.

The organs on chip allow for a drug to react to tissue in a more similar way to the body than it would in a petri dish, Georgescu said. Cells sense their environment very well, he added.

“We’re making the environment more complicated, making its spacial features complicated enough to match the native complexity of the organs,” he said. “When [cells] sense a softer environment, they start to behave more realistically. Their response to the drug is more realistic.”

Continue reading “This Penn-founded biotech company specializing in human ‘organs on chip’ raised $4M” at Technical.ly Philly. 

Originally posted in Penn Engineering Today.

Michael Mitchell on Keeping mRNA Vaccines Viable

A National Institute of Allergy and Infectious Diseases lab freezer used for COVID-19 vaccine research. Both of the current mRNA-based COVID vaccines require ultra-cold freezers to prevent their mRNA from degrading, spurring research into other ways to stabilize the molecule.

As the technology behind two of the COVID-19 vaccines, Messenger RNA (mRNA) is having a moment. A single-stranded counterpart to DNA, mRNA translates its genetic code into proteins; by injecting mRNA engineered to produce proteins found on the exterior of the virus, the vaccine can train a person’s immune system to recognize the real thing without making them sick.

However, because mRNA is a relatively unstable molecule, distributing these vaccines involves extra logistical challenges. Doses must be transported and stored at ultra-cold temperatures to make sure the mRNA inside doesn’t degrade and lose the genetic information it carries.

Michael Mitchell
Michael Mitchell

As mRNA vaccines and other therapies take off, researchers are looking for other ways to forestall this degradation. One of them is Michael J. Mitchell, Skirkanich Assistant Professor of Innovation in the Department of Bioengineering, who is studying the use of lipid nanoparticles to encapsulate and protect mRNA on its way into the cell. That sort of packaging would be particularly beneficial in proposed mRNA therapies for certain genetic disorders, which aim to deliver the correct protein-making instructions to specific organs, or even a fetus in utero.

But for stabilizing mRNA for vaccine distribution, many other strategies are being explored. In “Keeping covid vaccines cold isn’t easy. These ideas could help,” Wudan Yan of MIT Technology Review reached out to Mitchell for insight on LIONs, or lipid inorganic nanoparticles. These nanoparticles work the opposite way of Mitchell’s organic ones, with the mRNA stabilized by binding to their exteriors.

Continue reading at MIT Technology Review.

Originally posted in Penn Engineering Today.

‘RNA worked for COVID-19 vaccines. Could it be used to treat cancer and rare childhood diseases?’

William H. Peranteau, Michael J. Mitchell, Margaret Billingsley, Meghana Kashyap, and Rachel Riley (Clockwise from top left)

As COVID-19 vaccines roll out, the concept of using mRNA to fend off viruses has become a part of the public dialogue. However, scientists have been researching how mRNA can be used to in life-saving medical treatments well before the pandemic.

The “m” in “mRNA” is for “messenger.” A single-stranded counterpart to DNA, it translates the genetic code into the production of proteins, the building blocks of life. The Moderna and Pfizer COVID-19 vaccines work by introducing mRNA sequences that act as a set of instructions for the body to produce proteins that mimic parts of the virus itself. This prepares the body’s immune response to recognize the real virus and fight it off.

Because it can spur the production of proteins that the body can’t make on its own, mRNA therapies also have the potential to slow or prevent genetic diseases that develop before birth, such as cystic fibrosis and sickle-cell anemia.

However, because mRNA is a relatively unstable molecule that degrades quickly, it needs to be packaged in a way that maintains its integrity as its delivered to the cells of a developing fetus.

To solve this challenge, Michael J. Mitchell, Skirkanich Assistant Professor of Innovation in the Department of Bioengineering, is researching the use of lipid nanoparticles as packages that transport mRNA into the cell. He and William H. Peranteau, an attending surgeon in the Division of General, Thoracic and Fetal Surgery and the Adzick-McCausland Distinguished Chair in Fetal and Pediatric Surgery at Children’s Hospital of Philadelphia, recently co-authored a “proof-of-concept” paper investigating this technique.

In this study, published in Science Advances, Mitchel examined which nanoparticles were optimal in the transport of mRNA to fetal mice. Although no disease or organ was targeted in this study, the ability to administer mRNA to a mouse while still in the womb was demonstrated, and the results are promising for the next stages of targeted disease prevention in humans.

Mitchel spoke with Tom Avril at The Philadelphia Inquirer about the mouse study and its implications for treatment of rare infant diseases through the use of mRNA, ‘the messenger of life.’

Penn bioengineering professor Michael J. Mitchell, the other senior author of the mouse study, tested various combinations of lipids to see which would work best.

The appeal of the fatty substances is that they are biocompatible. In the vaccines, for example, two of the four lipids used to make the delivery spheres are identical to lipids found in the membranes of human cells — including plain old cholesterol.

When injected, the spheres, called nanoparticles, are engulfed by the person’s cells and then deposit their cargo, the RNA molecules, inside. The cells respond by making the proteins, just as they make proteins by following the instructions in the person’s own RNA. (Important reminder: The RNA in the vaccines cannot become part of your DNA.)

Among the different lipid combinations that Mitchell and his lab members tested, some were better at delivering their cargo to specific organs, such as the liver and lungs, meaning they could be a good vehicle for treating disease in those tissues.

Continue reading Tom Avril’s ‘RNA worked for COVID-19 vaccines. Could it be used to treat cancer and rare childhood diseases?’ at The Philadelphia Inquirer.