Tag: Cesar de la Fuente

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Penn Researchers Show ‘Encrypted’ Peptides Could be Wellspring of Natural Antibiotics

by Melissa Pappas

César de la Fuente, Ph.D.

While biologists and chemists race to develop new antibiotics to combat constantly mutating bacteria, predicted to lead to 10 million deaths by 2050, engineers are approaching the problem through a different lens: finding naturally occurring antibiotics in the human genome.

The billions of base pairs in the genome are essentially one long string of code that contains the instructions for making all of the molecules the body needs. The most basic of these molecules are amino acids, the building blocks for peptides, which in turn combine to form proteins. However, there is still much to learn about how — and where — a particular set of instructions are encoded.

Now, bringing a computer science approach to a life science problem, an interdisciplinary team of Penn researchers have used a carefully designed algorithm to discover a new suite of antimicrobial peptides, hiding deep within this code.

The study, published in Nature Biomedical Engineering, was led by César de la Fuente, Presidential Assistant Professor in Bioengineering, Microbiology, Psychiatry, and Chemical and Biomolecular Engineering, spanning both Penn Engineering and Penn Medicine, and his postdocs Marcelo Torres and Marcelo Melo. Collaborators Orlando Crescenzi and Eugenio Notomista of the University of Naples Federico II also contributed to this work.

“The human body is a treasure trove of information, a biological dataset. By using the right tools, we can mine for answers to some of the most challenging questions,” says de la Fuente. “We use the word ‘encrypted’ to describe the antimicrobial peptides we found because they are hidden within larger proteins that seem to have no connection to the immune system, the area where we expect to find this function.”

Read the full story in Penn Engineering Today.

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Penn Engineers Create Faster and Cheaper COVID-19 Testing With Pencil Lead

by Melissa Pappas

César de la Fuente, PhD

Testing is key to understanding and controlling the spread of COVID-19, which has already taken more than four million lives around the world. However, current tests are limited by the tradeoff between accuracy and the time it takes to analyze a sample.

Another challenge of current COVID-19 tests is cost. Most tests are expensive to produce and require trained personnel to administer and analyze them. Testing in low-and middle-income communities has therefore been largely inaccessible, leaving individuals at greater risk of viral spread.

To address cost, time and accuracy, a new electrochemical test developed by Penn researchers uses electrodes made from graphite — the same material found in pencil lead. Developed by César de la Fuente, Presidential Assistant Professor in Bioengineering,  Microbiology and Psychiatry with a secondary appointment in Chemical and Biomolecular Engineering, these electrodes reduce the cost to $1.50 per test and require only 6.5 minutes to deliver 100-pecent-accurate results from saliva samples and up to 88 percent accuracy in nasal samples.

While his previous research highlights the invention of RAPID (Real-time Accurate Portable Impedimetric Detection prototype 1.0), a COVID-19 testing kit which uses screen-printed electrodes, this new research published in PNAS presents LEAD (Low-cost Electrochemical Advanced Diagnostic), using the same concept as RAPID but with less expensive materials. De la Fuente’s current test reduces costs from $4.67 per test (RAPID) to $1.50 per test (LEAD) just by changing the building material of the electrodes.

“Both RAPID and LEAD work on the same principle of electrochemistry,” says de la Fuente. “However, LEAD is easier to assemble, it can be used by anyone and the materials are cheaper and more accessible than those of RAPID. This is important because we are using an abundant material, graphite, the same graphite used in pencils, to build the electrode to make testing more accessible to lower-income communities.”

This figure, adapted from the paper, shows the functionalization steps of LEAD which prepares the electrodes to bind to the sample. The height of the peaks indicates whether the sample is negative or positive. Because the SARS-CoV-2 spike protein in a positive sample binds to the electrode, it inhibits the emitted signal and produces a smaller peak.

Read the full story in Penn Engineering Today.

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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.

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Penn Health-Tech Q&A with César de la Fuente

Created in the lab of César de la Fuente, this miniaturized, portable version of rapid COVID-19 test, which is compatible with smart devices, can detect SARS-CoV-2 within four minutes with nearly 100% accuracy. (Image: Courtesy of César de la Fuente)

César de la Fuente, Presidential Assistant Professor in Bioengineering, Chemical and Biomolecular Engineering, Microbiology, and Psychiatry, was the inaugural recipient of the Nemirovsky Engineering and Medicine Opportunity (NEMO) Prize from Penn Health-Tech in 2020 for his low-cost, rapid COVID test. Now with promising results recently published in the journal Matter (showing 90 percent accuracy in as little as four minutes), Penn Health-Tech caught up with de la Fuente to discuss his experience over the past year:

“How did [your project] evolve in the past year?

‘We started with one prototype and now have three entirely different prototypes for the test. Two use electrochemistry, and we are now working on a new technology that uses calorimetry. With calorimetry, when the cotton swabs are exposed to the virus, they change color. This means users are able to see if they’re affected by a virus through a simple color change, making it more of a visual detection method.'”

Read the full Q&A in the Penn Health-Tech blog.

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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.

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Bioengineering Contributes to “New COVID-19 Testing Technology at Penn”

César de la Fuente, Ph.D., a Presidential Assistant Professor in Psychiatry, Microbiology, and Bioengineering, is leading a team to develop an electrode that can be easily printed at low cost to provide COVID-19 test results from your smart phone.

A recent Penn Medicine blog post surveys the efforts across Penn and the Perelman School of Medicine to develop novel says to detect SARS-CoV-2 and features several Department of Bioengineering faculty and Graduate Group members, including César de la Fuente, Presidential Assistant Professor in Psychiatry, Microbiology, and Bioengineering; Arupa Ganguly, Professor in Genetics; A.T. Charlie Johnson, Rebecca W. Bushnell Professor in Physics and Astronomy; Lyle Ungar, Professor in Computer and Information Science; and Ping Wang, Associate Professor in Pathology and Laboratory Medicine.

Read “We’ll Need More than Vaccines to Vanquish the Virus: New COVID-19 Testing Technology at Penn” by Melissa Moody in Penn Medicine News.

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One Step Closer to an At-home, Rapid COVID-19 Test

Created in the lab of César de la Fuente, this miniaturized, portable version of rapid COVID-19 test, which is compatible with smart devices, can detect SARS-CoV-2 within four minutes with nearly 100% accuracy. (Image: Courtesy of César de la Fuente)

The lab of Penn’s César de la Fuente sits at the interface of machines and biology, with much of its work focused on innovative treatments for infectious disease. When COVID-19 appeared, de la Fuente and his colleagues turned their attention to building a paper-based biosensor that could quickly determine the presence of SARS-CoV-2 particles from saliva and from samples from the nose and back of the throat. The initial iteration, called DETECT 1.0, provides results in four minutes with nearly 100% accuracy.

Clinical trials for the diagnostic began Jan. 5, with the goal of collecting 400 samples—200 positive for COVID-19, 200 negative—from volunteers who also receive a RT-PCR or “reverse transcription polymerase chain reaction” test. This will provide a comparison set against which to measure the biosensor to determine whether the results the researchers secured at the bench hold true for samples tested in real time. De la Fuente expects the trial will take about a month.

If all goes accordingly, he hopes these portable rapid breath tests could play a part in monitoring the COVID status of faculty, students, and staff around Penn.

César de la Fuente earned his bachelor’s degree in biotechnology, then a doctorate in microbiology and immunology and a postdoc in synthetic biology and computational biology. Combining these fields led him to the innovative work his lab, the Machine Biology Group, does today. (Photo: Eric Sucar)

Taking on COVID-19 research in this fashion made sense for this lab. “We’re the Machine Biology Group, and we’re interested in existing and emerging pathogens,” says de la Fuente, who has appointments in the Perelman School of Medicine and School of Engineering and Applied Science. “In this case, we’re using a machine to rapidly detect SARS-CoV-2.”

To this point in the pandemic, most SARS-CoV-2 diagnostics have used RT-PCR. Though effective, the technique requires significant space and trained workers to employ, and it is costly and takes hours or days to provide results. De la Fuente felt there was potential to create something inexpensive, quicker, and, perhaps most importantly, scalable.

Continue reading “One Step Closer to an At-home, Rapid COVID-19 Test,” by Michele Berger, at Penn Today.

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Engineering Bacteria-Killing Molecules from Wasp Venom

César de la Fuente, PhD

César de la Fuente a Presidential Assistant Professor in the Perelman School of Medicine’s departments of Psychiatry and Microbiology and Engineering’s department of Bioengineering, has racked up accolades for his innovative, computational approach to discovering new antibiotics.

Now, in his most recent study, de la Fuente has shown how these vital drugs might be derived from wasp venom.

The study, published in The Proceedings of the National Academy of Sciences, involved altering a highly toxic small protein from a common Asian wasp species, Vespula lewisii, the Korean yellow-jacket wasp. The alterations enhanced the molecule’s ability to kill bacterial cells while greatly reducing its ability to harm human cells. In animal models, de la Fuente and his colleagues showed that this family of new antimicrobial molecules made with these alterations could protect mice from otherwise lethal bacterial infections.

There is an urgent need for new drug treatments for bacterial infections, as many circulating bacterial species have developed a resistance to older drugs. The U.S. Centers for Disease Control & Prevention has estimated that each year nearly three million Americans are infected with antibiotic-resistant microbes and more than 35,000 die of them. Globally the problem is even worse: Sepsis, an often-fatal inflammatory syndrome triggered by extensive bacterial infection, is thought to have accounted for about one in five deaths around the world as recently as 2017.

“New antibiotics are urgently needed to treat the ever-increasing number of drug-resistant infections, and venoms are an untapped source of novel potential drugs. We think that venom-derived molecules such as the ones we engineered in this study are going to be a valuable source of new antibiotics,” says de la Fuente.

De la Fuente and his team started with a small protein, or “peptide,” called mastoparan-L, a key ingredient in the venom of Vespula lewisii wasps. Mastoparan-L-containing venom is usually not dangerous to humans in the small doses delivered by wasp stings, but it is quite toxic. It destroys red blood cells, and triggers a type of allergic/inflammatory reaction that in susceptible individuals can lead to a fatal syndrome called anaphylaxis—in which blood pressure drops and breathing becomes difficult or impossible.

Mastoparan-L (mast-L) also is known for its moderate toxicity to bacterial species, making it a potential starting point for engineering new antibiotics. But there are still some unknowns, including how to enhance its anti-bacterial properties, and how to make it safe for humans.

Continue reading at Penn Medicine News.

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César de la Fuente on AIChE’s 35 Under 35 List

César de la Fuente, PhD

César de la Fuente, Presidential Assistant Professor in Psychiatry, Microbiology, and Bioengineering, was named one of the American Institute of Chemical Engineers’ (AIChE) 35 members under 35 for 2020.

“The AIChE 35 Under 35 Award was founded to recognize young chemical engineers who have achieved greatness in their fields,” reads the 2020 award announcement. “The winners are a group of driven, engaged, and socially active professionals, representing the breadth and diversity that chemical engineering exemplifies.”

De la Fuente was named in the list’s “Bioengineering” category for his his lab’s work in machine biology. Their goal is to develop computer-made tools and medicines that will combat antibiotic resistance. De la Fuente has already been featured on several other young innovators lists, including MIT Technology Review’s 35 under 35 and GEN’s Top 10 under 40, both in 2019. His research in antibiotic resistance has been profiled in Penn Today and Penn Engineering Today, and he was recently awarded Penn Health-Tech’s inaugural NEMO Prize for his proposal to develop paper-based COVID diagnostic system that could capture viral particles on a person’s breath.

In addition to being named on the 2020 list, the honorees will receive a $500 prize and will be celebrated at the 2020 AIChE Annual Meeting this November.

Learn more about de la Fuente’s pioneering research on his lab website.

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César de la Fuente Wins Inaugural NEMO Prize, Will Develop Rapid COVID Virus Breath Tests

The paper-based tests could be integrated directly into facemasks and provide instant results at testing sites.

Cesar de la Fuente-Nunez, PhD

When Penn Health-Tech announced its Nemirovsky Engineering and Medicine Opportunity, or NEMO Prize, in February, the center’s researchers could only begin to imagine the impact the looming COVID-19 pandemic was about to unleash. But with the promise of $80,000 to support early-stage ideas at the intersection of engineering and medicine, the contest quickly sparked a winning innovation aimed at combating the crisis.

Judges from the University of Pennsylvania’s School of Engineering and Applied Sciences and Perelman School of Medicine awarded its first NEMO Prize to César de la Fuente, PhD, who proposed a paper-based COVID diagnostic system that could capture viral particles on a person’s breath, then give a result in a matter of seconds when taken to a testing site.

Similar tests for bacteria cost less than a dollar each to make. De la Fuente, a Presidential Assistant Professor in the departments of Psychiatry, Microbiology, and Bioengineering, is aiming to make COVID tests at a similar price point and with a smaller footprint so that they could be directly integrated into facemasks, providing further incentive for their regular use.

“Wearing a facemask is vital to containing the spread of COVID because, before you know you’re sick, they block your virus-carrying droplets so those droplets can’t infect others,” de la Fuente says. “What we’re proposing could eventually lead to a mask that can be infected by the virus and let you know that you’re infected, too.”

De la Fuente’s lab has conducted molecular dynamic simulations of the regions of the SARS-COV-2 spike protein (blue) that bind to the human ACE2 receptor (red and yellow).

De la Fuente’s expertise is in synthetic biology and molecular-scale simulations of disease-causing viruses and bacteria. Having such fine-grained computational models of these microbes’ binding sites allow de la Fuente to test them against massive libraries of proteins, seeing which bind best. Other machine learning techniques can then further narrow down the minimum molecular structures responsible for binding, resulting in functional protein fragments that are easier to synthesize and manipulate.

The spike-shaped proteins that give coronaviruses their crown-like appearance and name bind to a human receptor known as ACE2. De la Fuente and his colleagues are now aiming to characterize the molecular elements and environmental factors that would allow for the most precise, reliable detection of the virus.

Read the full story on the Penn Engineering blog.