BE/MEAM Seminar: “Microbes in Biomechanics” (Christopher J. Hernandez)

Speaker: Christopher J. Hernandez, Ph.D.
Professor, Sibley School of Mechanical and Aerospace Engineering, Cornell University
Adjunct Scientist, Hospital for Special Surgery

Date: Thursday, February 4, 2021
Time: 3:00-4:00 PM EST
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “Microbes in Biomechanics”

This seminar is jointly hosted by the Department of Bioengineering and the Department of Mechanical Engineering and Applied Mechanics.

Abstract:

The idea that mechanical stresses influence the growth and form of organs and organisms originated in the 1800s and is the basis for the modern study of biomechanics and mechanobiology. Biomechanics and mechanobiology are well studied in eukaryotic systems, yet eukaryotes represent only a small portion of the diversity and abundance of life on Earth. Bacteria exhibit broad influences on human health (as both pathogens and as beneficial components of the gut microbiome) and processes used in biotechnology and synthetic biology. Over the past eight years my group has explored mechanobiology within individual bacteria and the effects of changes in the composition of commensal bacterial communities on the biomechanics in the musculoskeletal system.

The ability of the bacteria to not only resist mechanical loads (biomechanics) but also to respond to changes in the mechanical environment (mechanobiology) is necessary for survival. Here I describe a novel microfluidic platform used to explore the biomechanics and mechanobiology of individual, live bacteria. I discuss work from my group demonstrating that mechanical stress within the bacterial cell envelope can influence the assembly and function of multicomponent efflux pumps used by bacteria to resist toxins and antibiotics. Additionally, I share some of our more recent work showing that mechanical stress and strain within the bacterial cell envelope can stimulate a bacterial two-component system controlling gene expression. Our findings demonstrate that bacteria, like mammalian cells, have mechanosensitive systems that are key to survival.

In musculoskeletal disease, bacteria are commonly viewed as sources of infection. However, in the past decade the studies by my group and others have suggested that commensal bacteria – the microbiome – can modulate the pathogenesis of musculoskeletal disorders. My group is among the first to study the effects of the gut microbiome on orthopaedic disorders. Here I provide an introduction to the microbiome and current concepts of how modifications to the gut microbiome could influence the musculoskeletal system. Specifically, I discuss studies from my group which are the first to demonstrate that the gut microbiome influences bone biomechanics and the development of infection of orthopaedic implants.

Bio:

Dr. Hernandez is Professor in the Sibley School of Mechanical and Aerospace Engineering at Cornell University and is an Adjunct Scientist at the Hospital for Special Surgery. Dr. Hernandez is a Fellow of the American Institute for Medical and Biological Engineering (AIMBE), the American Society of Mechanical Engineers (ASME), and the American Society for Bone and Mineral Research (ASBMR). He is the 2018 recipient of the Fuller Albright Award for Scientific Excellence from the American Society for Bone and Mineral Research. He has served on the Board of Directors of the Orthopaedic Research Society and the American Society for Bone and Mineral Research. His laboratory’s research currently focuses on the effects of the microbiome on bone and joint disorders, periprosthetic joint infection and the biomechanics and mechanobiology of bacteria.

hernandezresearch.com

Penn Engineering and CHOP Researchers Identify Nanoparticles that Could Be Used in Therapeutic mRNA Delivery before Birth

by Evan Lerner

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

Researchers at Children’s Hospital of Philadelphia and the School of Engineering and Applied Science at the University of Pennsylvania have identified ionizable lipid nanoparticles that could be used to deliver mRNA as part of fetal therapy. The proof-of-concept study, published today in Science Advances, engineered and screened a number of lipid nanoparticle formulations for targeting mouse fetal organs and has laid the groundwork for testing potential therapies to treat genetic diseases before birth.

“This is an important first step in identifying nonviral mediated approaches for delivering cutting-edge therapies before birth,” said co-senior author William H. Peranteau, MD, an attending surgeon in the Division of General, Thoracic and Fetal Surgery and the Adzick-McCausland Distinguished Chair in Fetal and Pediatric Surgery at CHOP. “These lipid nanoparticles may provide a platform for in utero mRNA delivery, which would be used in therapies like fetal protein replacement and gene editing.”

Michael J. Mitchell, Skirkanich Assistant Professor of Innovation in Penn Engineering’s Department of Bioengineering, is the other co-senior author of the study. The co-first authors are Mitchell Lab members Rachel Riley, a postdoctoral fellow, and Margaret Billingsley, a graduate student, and Peranteau Lab member Meghana Kashyap, a research fellow.

Recent advances in DNA sequencing technology and prenatal diagnostics have made it possible to diagnose many genetic diseases before birth. Some of these diseases are treated by protein or enzyme replacement therapies after birth, but by then, some of the damaging effects of the disease have taken hold. Thus, applying therapies while the patient is still in the womb has the potential to be more effective for some conditions. The small fetal size allows for maximal therapeutic dosing, and the immature fetal immune system may be more tolerant of replacement therapy.

Read the full story in Penn Engineering Today.

NB: Rachel Riley is now Assistant Professor in Biomedical Engineering at Rowan University.

Studying ‘Hunters and Busybodies,’ Penn and American University Researchers Measure Different Types of Curiosity

by Melissa Pappas

Knowledge networks were created as participants browsed Wikipedia, where pages became nodes and relatedness between pages became edges. Two diverging styles emerged — “the busybody” and “the hunter.” (Illustrations by Melissa Pappas)

Curiosity has been found to play a role in our learning and emotional well-being, but due to the open-ended nature of how curiosity is actually practiced, measuring it is challenging. Psychological studies have attempted to gauge participants’ curiosity through their engagement in specific activities, such as asking questions, playing trivia games, and gossiping. However, such methods focus on quantifying a person’s curiosity rather than understanding the different ways it can be expressed.

Efforts to better understand what curiosity actually looks like for different people have underappreciated roots in the field of philosophy. Varying styles have been described with loose archetypes, like “hunter” and “busybody” — evocative, but hard to objectively measure when it comes to studying how people collect new information.

A new study led by researchers at the University of Pennsylvania’s School of Engineering and Applied Science, the Annenberg School for Communication, and the Department of Philosophy and Religion at American University, uses Wikipedia browsing as a method for describing curiosity styles. Using a branch of mathematics known as graph theory, their analysis of curiosity opens doors for using it as a tool to improve learning and life satisfaction.

The interdisciplinary study, published in Nature Human Behavior, was undertaken by Danielle Bassett, J. Peter Skirkanich Professor in Penn Engineering’s Departments of Bioengineering and Electrical and Systems Engineering, David Lydon-Staley, then a post-doctoral fellow in her lab, now an assistant professor in the Annenberg School of Communication, two members of Bassett’s Complex Systems Lab, graduate student Dale Zhou and postdoctoral fellow Ann Sizemore Blevins, and Perry Zurn, assistant professor from American University’s Department of Philosophy.

“The reason this paper exists is because of the participation of many people from different fields,” says Lydon-Staley. “Perry has been researching curiosity in novel ways that show the spectrum of curious practice and Dani has been using networks to describe form and function in many different systems. My background in human behavior allowed me to design and conduct a study linking the styles of curiosity to a measurable activity: Wikipedia searches.”

Zurn’s research on how different people express curiosity provided a framework for the study.

Read the full story in Penn Engineering Today.

BE Seminar: “Designing Biology for Detection and Control” (Pamela A. Silver)

Speaker: Pamela A. Silver, Ph.D.
Elliot T. and Onie H. Adams Professor of Biochemistry and Systems Biology
Harvard Medical School

Date: Thursday, January 28, 2021
Time: 3:00-4:00 PM EST
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “Designing Biology for Detection and Control”

Abstract:

The engineering of Biology presents infinite opportunities for therapeutic design, diagnosis, and prevention of disease. We use what we know from Nature to engineer systems with predictable behaviors. We also seek to discover new natural strategies to then re-engineer. I will present concepts and experiments that address how we approach these problems in a systematic way. Conceptually, we seek to both design cells and proteins to control disease states and to detect and predict the severity of emerging pathogens. For example, we have engineered components of the gut microbiome to act therapeutics for infectious disease, proteins to prolong cell states, living pathogen sensors and high throughput analysis to predict immune response of emerging viruses.

Bio:

Pamela Silver is the Adams Professor of Biochemistry and Systems Biology at Harvard Medical School and the Wyss Institute for Biologically Inspired Engineering. She received her BS in Chemistry and PhD in Biochemistry from the University of California. Her work has been recognized by an Established Investigator of the American Heart Association, a Research Scholar of the March of Dimes, an NSF Presidential Young Investigator Award, Claudia Adams Barr Investigator, an NIH MERIT award, the Philosophical Society Lecture, a Fellow of the Radcliffe Institute, and election to the American Academy of Arts and Sciences. She is among the top global influencers in Synthetic Biology and her work was named one of the top 10 breakthroughs by the World Economic Forum. She serves on the board of the Internationally Genetics Engineering Machines (iGEM) Competition and is member of the National Science Advisory Board for Biosecurity. She has led numerous projects for ARPA-E, iARPA and DARPA. She is the co-founder of several Biotech companies including most recently KulaBio and serves on numerous public and private advisory boards.

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.

Penn, Carnegie Mellon and Johns Hopkins to Develop New Turing Tests, Investigate How AI Can Become More Like Biological Intelligence

by Evan Lerner

While artificial intelligence is becoming a bigger part of nearly every industry and increasingly present in everyday life, even the most impressive AI is no match for a toddler, chimpanzee, or even a honeybee when it comes to learning, creativity, abstract thinking or connecting cause and effect in ways they haven’t been explicitly programmed to recognize.

This discrepancy gets at one of the field’s fundamental questions: what does it mean to say an artificial system is “intelligent” in the first place?

Konrad Kording, Timothy Verstynen, Joshua T. Vogelstein, and Leyla Isik (clockwise from top left)

Seventy years ago, Alan Turing famously proposed such a benchmark; a machine could be considered to have artificial intelligence if it could successfully fool a person into thinking it was a human as well. Now, many artificial systems could pass a “Turing Test” in certain limited domains, but none come close to imitating the holistic sense of intelligence we recognize in animals and people.

Understanding how AI might someday be more like this kind of biological intelligence — and developing new versions of the Turing Test with those principles in mind — is the goal of a new collaboration between researchers at the University of Pennsylvania, Carnegie Mellon University and Johns Hopkins University.

The project, called “From Biological Intelligence to Human Intelligence to Artificial General Intelligence,” is led by Konrad Kording, a Penn Integrates Knowledge Professor with appointments in the Departments of Bioengineering and Computer and Information Science in Penn Engineering and the Department of Neuroscience at Penn’s Perelman School of Medicine. Kording will collaborate with Timothy Verstynen of Carnegie Mellon University, as well Joshua T. Vogelstein and Leyla Isik, both of Johns Hopkins University, on the project.

Read the full story on Penn Engineering Today.

BE Seminar: “Deconstructing and Reconstructing Human Tissues” (Kelly Stevens)

Kelly Stevens, PhD

Speaker:  Kelly Stevens, Ph.D.
Assistant Professor, Department of Bioengineering and Department of Laboratory Medicine & Pathology
University of Washington

Date: Thursday, January 21, 2021
Time: 3:00-4:00 PM EST
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “Deconstructing and Reconstructing Human Tissues”

Abstract:

Although much progress has been made in building artificial human tissues over the past several decades, replicating complex tissue structure remains an enormous challenge. To overcome this challenge, our field first needs to create better three-dimensional spatial maps, or “blueprints” of human tissues and organs. We also need to then understand how these spatial blueprints encode positional processes in tissues. My group is developing new advanced biofabrication technologies to address both of these issues. Here, I will describe some of our work in both attaining transcriptomic maps as well as in controlling spatiogenetic wiring of human artificial tissues.

Bio:

Dr. Kelly Stevens is an Assistant Professor of Bioengineering, and Laboratory Medicine & Pathology at the University of Washington. Dr. Stevens’ research focuses on mapping and building artificial human tissues to treat liver and heart disease. She has made contributions to improve human cell sourcing, vascularization, structure and physiology of human bioartificial tissues. Dr. Stevens has received several awards in recognition of this work, including the NIH New Innovator Award, BMES CMBE Rising Star Award, John Tietze Stem Cell Scientist Award, and Gree Foundation Scholar Award.

Bioengineering Faculty Contribute to New Treatment That “Halts Osteoarthritis-Like Knee Cartilage Degeneration”

A recent study published in Science Translational Medicine announces a discovery which could halt cartilage degeneration caused by osteoarthritis: “These researchers showed that they could target a specific protein pathway in mice, put it into overdrive and halt cartilage degeneration over time. Building on that finding, they were able to show that treating mice with surgery-induced knee cartilage degeneration through the same pathway via the state of the art of nanomedicine could dramatically reduce the cartilage degeneration and knee pain.” This development could eventually lead to treating osteoarthritis with injection rather than more complicated surgery.

Among a team of Penn Engineering and Penn Medicine researchers, the study was co-written by Zhiliang Cheng, Research Associate Professor in Bioengineering, Andrew Tsourkas, Professor in Bioengineering, and Robert Mauck, Mary Black Ralston Professor in Bioengineering and Orthopaedic Surgery. The lead author was Yulong Wei of the Department of Orthopaedic Surgery and the McKay Orthopaedic Research Laboratory.

Read the press release in Penn Medicine News.

Christian Figueroa-Espada Named 2020-2021 Hispanic Scholarship Fund Scholar

Christian Figueroa-Espada

Christian Figueroa-Espada, a Penn Bioengineering Ph.D. student and National Science Foundation (NSF) Fellow, was selected as a Hispanic Scholarship Fund (HSF) Scholar from a highly-competitive pool of 85,000 applicants for their 2020-2021 program. One of only 5,100 awardees, Figueroa-Espada’s scholarship comes from the Toyota Motor North America Program. As an HSF Scholar, he has access to a full range of Scholar Support Services, such as career coaching, internship, and full-time employment opportunities, mentoring, leadership development, and wellness resources, including tools for self-advocacy, well-being, and knowledge building.

Born and raised in the Island of Enchantment, Puerto Rico, Figueroa-Espada received his B.S. in Mechanical Engineering from the University of Puerto Rico at Mayagüez, and is currently a second-year Ph.D. student in the lab of Michael J. Mitchell, Skirkanich Assistant Professor of Innovation in Bioengineering, where he is funded by the National Science Foundation Graduate Research Fellowship Program (NSF GRFP), the Graduate Education for Minorities (GEM) Fellowship Program, and the William Fontaine Fellowship. His research interests lie in the interface of biomaterials, drug delivery, and immunology – designing RNAi therapeutics for the reprogramming of the tumor microenvironment. His current project focuses on polymer-lipid drug delivery systems to study potential strategies to prevent homing and proliferation of multiple myeloma cancer within the bone marrow microenvironment. This project is part of the Mitchell lab’s recent National Institutes of Health (NIH) New Innovator Award.

“Chris has really hit the ground running on his Ph.D. studies at Penn Bioengineering, developing a new bone marrow-targeted nanoparticle platform to disrupt the spread of multiple myeloma throughout the body,” says Mitchell. “I’m very hopeful that this prestigious fellowship from HSF will permit him to make important contributions to nanomedicine and cancer research.”

Figueroa-Espada’s passion for giving back to his community has allowed him to be involved in many mentorship programs as part of his roles in the Society of Hispanics and Professional Engineers (SHPE), the National Society of Professional Engineers (NSPE), the Society of Women Engineers (SWE), and the Graduate Association of Bioengineers (GABE). He continues with his fervent commitment, now working with the Penn chapter of the Society for Advancement of Chicanos/Hispanics and Native Americans in Science (SACNAS), and the Penn Interdisciplinary Network for Scientists Promoting Inclusion, Retention, and Equity (INSPIRE) coalition where he plans on leading initiatives that aim to enhance diversity and student participation in science, especially students from historically marginalized groups.

“This fellowship, along with my NSF Graduate Research Fellowship, GEM Fellowship, and William Fontaine Fellowship through the University of Pennsylvania, make my research on nanoparticle-based RNA therapeutics for the reprogramming of the tumor microenvironment to treat malignancies and overcome drug resistance possible,” says Figueroa-Espada. “While my professional goal is to stay in academia and lead a research lab, my personal goal is to become whom I needed: a role model within the Latino STEM community, hoping to address many of the difficulties that impede Latino students’ success in higher education, and thanks to Toyota Motor/HSF, NSF, and GEM, I am one step closer to meeting these goals.”

Student Spotlight: Sonia Bansal

Sonia Bansal, Ph.D.

Next up in the Penn Bioengineering student spotlight series is Sonia Bansal. Sonia got her B.S. in Biomedical Engineering at Columbia University in 2014. She then came to Penn, where she recently got her Ph.D. in September of 2020 in Bioengineering under the advisement of Robert Mauck, Mary Black Ralston Professor of Orthopaedic Surgery and Professor of Bioengineering. Her dissertation is entitled “Functional and Structural Remodeling of the Meniscus with Growth and Injury” and focuses on the ways the knee meniscus changes while being actively loaded (growth) and under aberrant loading (injurious) conditions. She has presented her work internationally and has first authored four papers, with two more in preparation. She is passionate about K-12 STEM outreach and teaching at the collegiate level. She has been on the teaching team for six classes in the department, and is the first recipient of the Graduate Fellowship for Teaching Excellence from the Bioengineering department.

What drew you to the field of Bioengineering?
I first got interested in Bioengineering when I realized that it would let me merge my interests in biology and the human body with my desire to solve big questions by building and creating solutions. I applied to college knowing it was what I wanted to study.

What kind of research do you conduct, and what is the focus of your thesis?
My research is focused on the knee meniscus, specifically the impacts of its complex extracellular matrix and how that matrix changes during growth and after meniscal injury. My interests are largely translational, and in the future, I’d like to think about how we can use preclinical animal models to create effective therapeutics and drive clinical decision making in the orthopedic space.

What did you study for your undergraduate degree? How does it pair with the work you’re doing now, and what advice would you give to your undergraduate self?
I studied Biomedical Engineering during my undergraduate education and worked in cartilage tissue engineering. These experiences helped guide me to my Ph.D. work here at Penn. The two pieces of advice I’d give my undergraduate self is to ask for help and that it’s important to get more than five hours of sleep a night.

What’s your favorite thing to do on Penn’s campus or in Philly?
My favorite thing to do on campus was to read papers/write lectures/work on grants at a local coffee shop. I used to go to HubBub when it still existed, Saxby’s, and United By Blue.

Have you done or learned anything new or interesting during quarantine?
I have embarked on a journey in culinary fermentation (variety of pickles and sourdough, of course), and recently started homebrewing!