Tag: microbiology

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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.

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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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Immunology/BE Seminar: “Engineering Next-Generation CAR-T Cells for Cancer Immunotherapy” (Yvonne Chen)

Yvonne Chen, PhD

This event is part of the Penn Institute for Immunology Colloquium seminar series in conjunction with the Department of Bioengineering.

Speaker: Yvonne Chen, Ph.D.
Associate Professor, Microbiology, Immunology & Molecular Genetics
University of California, Los Angeles

Date: Tuesday, November 17, 2020
Time: 4:00-5:00 PM EST
This event will be held virtually on Bluejeans.

Title: “Engineering Next-Generation CAR-T Cells for Cancer Immunotherapy”

Abstract:

The adoptive transfer of T cells expressing chimeric antigen receptors (CARs) has demonstrated clinical efficacy in the treatment of advanced cancers, with anti-CD19 CAR-T cells achieving up to 90% complete remission among patients with relapsed B-cell malignancies. However, challenges such as antigen escape and immunosuppression limit the long-term efficacy of adoptive T-cell therapy. Here, I will discuss the development of next-generation T cells that can target multiple cancer antigens and resist immunosuppression, thereby increasing the robustness of therapeutic T cells against tumor defense mechanisms. Specifically, I will discuss the development of multi-input receptors and T cells that can interrogate intracellular antigens. I will also discuss the engineering of T cells that can effectively convert TGF-beta from a potent immunosuppressive cytokine into a T-cell stimulant. This presentation will highlight the potential of synthetic biology in generating novel mammalian cell systems with multifunctional outputs for therapeutic applications.

Bio:

Dr. Yvonne Chen is an Associate Professor of Microbiology, Immunology, and Molecular Genetics at the University of California, Los Angeles. She is also a faculty, by courtesy, in the Department of Chemical and Biomolecular Engineering. The Chen Laboratory focuses on applying synthetic biology and biomolecular engineering techniques to the development of novel mammalian-cell systems. The Chen Lab’s work on engineering next-generation T-cell therapies for cancer has been recognized by the NIH Director’s Early Independence Award, the NSF CAREER Award, the Hellman Fellowship, the ACGT Young Investigator Award in Cell and Gene Therapy for Cancer, the Mark Foundation Emerging Leader Award, and the Cancer Research Institute Lloyd J. Old STAR Award. Prior to joining UCLA in 2013, Yvonne was a Junior Fellow in the Harvard Society of Fellows. She received postdoctoral training at the Center for Childhood Cancer Research within the Seattle Children’s Research Institute, and in the Department of Systems Biology at Harvard Medical School. Yvonne received her B.S. in Chemical Engineering from Stanford University and her Ph.D. in Chemical Engineering from the California Institute of Technology.