The rise of drug-resistant bacteria infections is one of the world’s most severe global health issues, estimated to cause 10 million deaths annually by the year 2050. Some of the most virulent and antibiotic-resistant bacterial pathogens are the leading cause of life-threatening, hospital-acquired infections, particularly dangerous for immunocompromised and critically ill patients. Traditional and continual synthesis of antibiotics will simply not be able to keep up with bacteria evolution.
To avoid the continual process of synthesizing new antibiotics to target bacteria as they evolve, Penn Engineers have looked at a new, natural resource for antibiotic molecules.
A recent study on the search for encrypted peptides with antimicrobial properties in the human proteome has located naturally occurring antibiotics within our own bodies. By using an algorithm to pinpoint specific sequences in our protein code, a team of Penn researchers along with collaborators, led by César de la Fuente, Presidential Assistant Professor in Psychiatry, Bioengineering, Microbiology, and Chemical and Biomolecular Engineering, and Marcelo Torres, a post doc in de la Fuente’s lab, were able to locate novel peptides, or amino acid chains, that when cleaved, indicated their potential to fend off harmful bacteria.
Now, in a new study published in ACS Nano, the team along with Angela Cesaro, the lead author and post doc in de la Fuente’s lab, have identified three distinct antimicrobial peptides derived from a protein in human plasma and demonstrate their abilities in mouse models. Angela Cesaro performed a great part of the activities during her PhD under the supervision of corresponding author, Professor Angela Arciello, from the University of Naples Federico II. The collaborative study also includes Utrecht University in the Netherlands.
“We identified the cardiovascular system as a hot spot for potential antimicrobials using an algorithmic approach,” says de la Fuente. “Then we looked closer at a specific protein in the plasma.”
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.
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.”
Yogesh Goyal, Ph.D., a postdoctoral researcher in Genetics and Bioengineering, has been selected as a 2021 STAT Wunderkind, which honors the “next generation of scientific superstars.” Goyal’s research is centered around developing novel mathematical and experimental frameworks to study how a rare subpopulation of cancer cells are able to survive drug therapy and develop resistance, resulting in relapse in patients. In particular, his work provides a view of different paths that single cancer cells take when becoming resistant, at unprecedented resolution and scale. This research aims to help devise novel therapeutic strategies to combat the challenge of drug resistance in cancer.
Goyal is a Jane Coffin Childs Postdoctoral Fellow in the systems biology lab of Arjun Raj, Professor in Bioengineering and Genetics at Penn. He will begin an appointment as Assistant Professor in the Department of Cell and Developmental Biology (CDB) in the Feinberg School of Medicine at Northwestern University in spring 2022.
Speaker: Emma Chory, Ph.D.
Sculpting Evolution Laboratory
Massachusetts Institute of Technology
Date: Thursday, October 21, 2021
Time: 3:30-4:30 PM EDT
Zoom – check email for link or contact email@example.com
Room: Moore 216
Abstract: Evolution occurs when selective pressures from the environment shape inherited variation over time. Within the laboratory, evolution is commonly used to engineer proteins and RNA, but experimental constraints have limited our ability to reproducibly and reliably explore key factors such as population diversity, the timing of environmental changes, and chance. We developed a high-throughput system for the analytical exploration of molecular evolution using phage-based mutagenesis to evolve many distinct classes of biomolecules simultaneously. In this talk, I will describe the development of our open-source python:robot integration platform which enables us to adjust the stringency of selection in response to real-time evolving activity measurements and to dissect the historical, environmental, and random factors governing biomolecular evolution. Finally, I will talk about our many on-going projects which utilize this system to evolve previously intractable biomolecules using novel small-molecule substrates to target the undruggable proteome.
Emma Chory Bio: Emma Chory is a postdoctoral fellow in the Sculpting Evolution Group at MIT, advised by Kevin Esvelt and Jim Collins. Emma’s research utilizes directed evolution, robotics, and chemical biology to evolve biosynthetic pathways for the synthesis of novel peptide-based therapeutics. Emma obtained her PhD in Chemical Engineering in the laboratory of Gerald Crabtree at Stanford University. She is the recipient of the NSF Graduate Research Fellowship and a pre- and postdoctoral NIH NRSA Fellowship.
Now, in her latest exhibition, Kamen has created a series of pieces that highlight how the creative processes in art and science are interconnected. In “Reveal: The Art of Reimagining Scientific Discovery,” Kamen chronicles her own artistic process while providing a space for self-reflection that enables viewers to see the relationship between science, art, and their own creativity.
“Reveal: The Art of Reimagining Scientific Discovery,” presented by the Alper Initiative for Washington Art and curated by Sarah Tanguy, is on display at the American University Museum in Washington, D.C., until Dec. 12.
The exhbition catalog, which includes an essay on “Radicle Curiosity” by Perry Zurn and Dani S. Bassett, can be viewed online.
“I am so excited for Yogesh beginning his faculty career,” Raj says. “He is a wonderful scientist with a sense of aesthetics. His work is simultaneously significant and elegant, a powerful combination.”
With a unique background in engineering, developmental biology, biophysical modeling, and single-cell biology, Yogesh develops quantitative approaches to problems in developmental biology and cancer drug resistance. As a postdoc, Yogesh developed theoretical and experimental lineage tracing approaches to study how non-genetic fluctuations may arise within genetically identical cancer cells and how these fluctuations affect the outcomes upon exposure to targeted therapy drugs. The Goyal Lab at Northwestern will “combine novel experimental, computational, and theoretical frameworks to monitor, perturb, model, and ultimately control single-cell variabilities and emergent fate choices in development and disease, including cancer and developmental disorders.”
“I am excited to start a new chapter in my academic career at Northwestern University,” Goyal says. “I am grateful for my time at Penn Bioengineering, and I thank my mentor Arjun Raj and the rest of the lab members for making this time intellectually and personally stimulating.”
Congratulations to Dr. Goyal from everyone at Penn Bioengineering!
A new study from the Addiction, Health, & Adolescence (AHA!) Lab at the Annenberg School for Communication at the University of Pennsylvania found that men are over-cited and women are under-cited in the field of Communication. The researchers’ findings indicate that this problem is most persistent in papers authored by men.
“Despite known limitations in their use as proxies for research quality, we often turn to citations as a way to measure the impact of someone’s research,” says Professor David Lydon-Staley, “so it matters for individual researchers if one group is being consistently under-cited relative to another group. But it also matters for the field in the sense that if people are not citing women as much as men, then we’re building the field on the work of men and not the work of women. Our field should be representative of all of the excellent research that is being undertaken, and not just that of one group.”
The AHA! Lab is led by David Lydon-Staley, Assistant Professor of Communication and former postdoc in the Complex Systems lab of Danielle Bassett, J. Peter Skirkanich Professor in Bioengineering and in Electrical and Systems Engineering in the School of Engineering and Applied Science. Dr. Bassett and Bassett Lab members Dale Zhou and Jennifer Stiso, graduate students in the Perelman School of Medicine, also contributed to the study.
The Department of Bioengineering is proud to congratulate Claudia Loebel, M.D., Ph.D. on her appointment as Assistant Professor in the Department of Materials Science and Engineering at the University of Michigan. Loebel is part of the University of Michigan’s Biological Sciences Scholar program, which recruits junior instructional faculty in major areas of biomedical investigation. Loebel’s appointment will begin in Fall 2021.
Loebel got her M.D. in 2011 from Martin-Luther University in Halle-Wittenberg, Germany and her Ph.D. in Health Sciences and Technology from ETH Zurich, Switzerland in 2016. There she worked under her advisors Professors Marcy Zenobi-Wong from ETH Zurich and David Eglin from AO Research Institute Davos. At Penn, she conducted postdoctoral research in the Polymeric Biomaterials Laboratory of Jason Burdick, Robert D. Bent Professor in Bioengineering, and as a Visiting Research Scholar in the Mauck Laboratory of the McKay Orthopaedic Research Laboratory in the Perelman School of Medicine.
Loebel was awarded a K99/R00 Pathway to Independence Award through the National Institutes of Health (NIH), which supports her remaining time as a postdoc as well as her time as an independent investigator at the University of Michigan. Loebel is excited about training the next generation of scientists and engineers and being part of their journey in becoming independent and diverse thinkers.
Loebel’s research area is inspired by the interface between material science and regenerative engineering and how it can address specific problems related to tissue development, repair, and regeneration. By developing mechanically and strucatally dynamic biomaterials, microfabrication, and matrix manipulation techniques her works aim to recreate complex cell-matrix interactions and model tissue morphogenesis and disease. The ultimate goal of her research is to use these engineered systems to develop and translate more effective therapeutic treatments for diseases such as fibrotic, inflammatory, and congenital disorders. Her lab’s work will initially focus on developing engineering lung alveolar organoids, aiming to build models of acute and chronic pulmonary diseases and for personalized medicine.
Loebel says, “I am grateful to all my Ph.D. and postdoc mentors for their continuous support and especially Jason who, over the last few years, has trained me in becoming an independent scientist and mentor. This transition would not have been possible without such a great mentor team behind me.”
Congratulations Dr. Loebel from everyone at Penn Bioengineering!
New research from Robert Mauck, Mary Black Ralston Professor in Orthopaedic Surgery and Bioengineering and Director of Penn Medicine’s McKay Orthopaedic Research Laboratory, announces a “new biosealant therapy may help to stabilize injuries that cause cartilage to break down, paving the way for a future fix or – even better – begin working right away with new cells to enhance healing.” Their research was published in Advanced Healthcare Materials. The study’s lead author was Jay Patel, a former postdoctoral fellow in the McKay Lab and now Assistant Professor at Emory University and was contributed to by Claudia Loebel, a postdoctoral research in the Burdick lab and who will begin an appointment as Assistant Professor at the University of Michigan in Fall 2021. In addition, the technology detailed in this publication is at the heart of a new company (Forsagen LLC) spun out of Penn with support from the Penn Center for Innovation (PCI) Ventures Program, which will attempt to spearhead the system’s entry into the clinic. It is co-founded by both Mauck and Patel, along with study co-author Jason Burdick, Professor in Bioengineering, and Ana Peredo, a PhD student in Bioengineering.
Parkes will use the BBRF’s support to continue his research examining the link between the symptoms of mental illness and the brain. In particular, he seeks to uncover how individual patterns of abnormal neurodevelopment link to, and predict, the emergence of psychosis symptoms through childhood and adolescence using longitudinal data. In turn, Parkes’ work will discover prognostic biomarkers for the psychosis spectrum that will help inform clinical outcome tracking.
“I am honored to have been selected for a Young Investigator Grant from the BBRF this year,” Parkes says. “This award will support me to conduct research that I believe will make real inroads into understanding the pathways that link abnormalities in neurodevelopment to the symptoms of psychosis. I feel grateful for the opportunity to complete my postdoctoral training at Penn. Penn has connected me with wonderful people who I’m sure will be lifelong mentors, colleagues, and peers.”
The BBRF Young Investigator Grants are valued at more than $10.3 million and are awarded annually to 150 of the world’s most promising young scientists to support the work of early career investigators with innovative ideas for groundbreaking neurobiological research seeking to identify causes, improve treatments, and develop prevention strategies for psychiatric disorders.
Read more about the BBRF 2020 Young Investigators here.