Category: faculty

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Penn Bioengineering and COVID-19

A message from Penn Bioengineering Professor and Chair Ravi Radhakrishnan:

In response to the unprecedented challenges presented by the global outbreak of the novel coronavirus SARS-CoV-2, Penn Bioengineering’s faculty, students, and staff are finding innovative ways of pivoting their research and academic projects to contribute to the fight against COVID-19. Though these projects are all works in progress, I think it is vitally important to keep those in our broader communities informed of the critical contributions our people are making. Whether adapting current research to focus on COVID-19, investing time, technology, and equipment to help health care infrastructure, or creating new outreach and educational programs for students, I am incredibly proud of the way Penn Bioengineering is making a difference. I invite you to read more about our ongoing projects below.

RESEARCH

Novel Chest X-Ray Contrast

David Cormode, Associate Professor of Radiology and Bioengineering

Nanomedicine and Molecular Imaging Lab

Peter Noel, Assistant Professor of Radiology and BE Graduate Group Member

Laboratory for Advanced Computed Tomography Imaging

The Cormode and Noel labs are working to develop dark-field X-ray imaging, which may prove very helpful for COVID patients. It involves fabricating diffusers that incorporate gold nanoparticles to modify the X-ray beam. This method gives excellent images of lung structure. Chest X-ray is being used on the front lines for COVID patients, and this could potentially be an easy to implement modification of existing X-ray systems. The additional data give insight into the health state of the microstructures (alveoli) in the lung. This new contrast mechanics could be an early insight into the disease status of COVID-19 patients. For more on this research, see Cormode and Noel’s chapter in the forthcoming volume Spectral, Photon Counting Computed Tomography: Technology and Applications, edited by Katsuyuki Taguchi, Ira Blevis, and Krzysztof Iniewski (Routledge 2020).

Immunotherapy

Michael J. Mitchell, Skirkanich Assistant Professor of Innovation in Bioengineering

Mitchell Lab

Mike Mitchell is working with Saar Gill (Penn Medicine) on engineering drug delivery technologies for COVID-19 mRNA vaccination. He is also developing inhalable drug delivery technologies to block COVID-19 internalization into the lungs. These new technologies are adaptations of prior research published Volume 20 of Nano Letters (“Ionizable Lipid Nanoparticle-Mediated mRNA Delivery for Human CAR T Cell Engineering” January 2020) and discussed in Volume 18 of Nature Reviews Drug Discovery (“Delivery Technologies for Cancer Immunotherapy” January 2019).

Respiratory Distress Therapy Modeling

Ravi Radhakrishnan, Professor, and Chair of Bioengineering and Professor of Chemical and Biomolecular Engineering

Radhakrishnan Lab

Computational Models for Targeting Acute Respiratory Distress Syndrome (ARDS). The severe forms of COVID-19 infections resulting in death proceeds by the propagation of the acute respiratory distress syndrome or ARDS. In ARDS, the lungs fill up with fluid preventing oxygenation and effective delivery of therapeutics through the inhalation route. To overcome this major limitation, delivery of antiinflammatory drugs through the vasculature (IV injection) is a better approach; however, the high injected dose required can lead to toxicity. A group of undergraduate and postdoctoral researchers in the Radhakrishnan Lab (Emma Glass, Christina Eng, Samaneh Farokhirad, and Sreeja Kandy) are developing a computational model that can design drug-filled nanoparticles and target them to the inflamed lung regions. The model combines different length-scales, (namely, pharmacodynamic factors at the organ scale, hydrodynamic and transport factors in the tissue scale, and nanoparticle-cell interaction at the subcellular scale), into one integrated framework. This targeted approach can significantly decrease the required dose for combating ARDS. This project is done in collaboration with Clinical Scientist Dr. Jacob Brenner, who is an attending ER Physician in Penn Medicine. This research is adapted from prior findings published in Volume 13, Issue 4 of Nanomedicine: Nanotechnology, Biology and Medicine: “Mechanisms that determine nanocarrier targeting to healthy versus inflamed lung regions” (May 2017).

Diagnostics

Sydney Shaffer, Assistant Professor of Bioengineering and Pathology and Laboratory Medicine

Syd Shaffer Lab

Arjun Raj, Professor of Bioengineering

Raj Lab for Systems Biology

David Issadore, Associate Professor of Bioengineering and Electrical and Systems Engineering

Issadore Lab

Arjun Raj, David Issadore, and Sydney Shaffer are working on developing an integrated, rapid point-of-care diagnostic for SARS-CoV-2 using single molecule RNA FISH. The platform currently in development uses sequence specific fluorescent probes that bind to the viral RNA when it is present. The fluorescent probes are detected using a iPhone compatible point-of-care reader device that determines whether the specimen is infected or uninfected. As the entire assay takes less than 10 minutes and can be performed with minimal equipment, we envision that this platform could ultimately be used for screening for active COVID19 at doctors’ offices and testing sites. Support for this project will come from a recently-announced IRM Collaborative Research Grant from the Institute of Regenerative Medicine with matching funding provided by the Departments of Bioengineering and Pathology and Laboratory Medicine in the Perelman School of Medicine (PSOM) (PI’s: Sydney Shaffer, Sara Cherry, Ophir Shalem, Arjun Raj). This research is adapted from findings published in the journal Lab on a Chip: “Multiplexed detection of viral infections using rapid in situ RNA analysis on a chip” (Issue 15, 2015). See also United States Provisional Patent Application Serial No. 14/900,494 (2014): “Methods for rapid ribonucleic acid fluorescence in situ hybridization” (Inventors: Raj A., Shaffer S.M., Issadore D.).

HEALTH CARE INFRASTRUCTURE

Penn Health-Tech Coronavirus COVID-19 Collaborations

Brian Litt, Professor of Bioengineering, Neurology, and Neurosurgery

Litt Lab

In his role as one of the faculty directors for Penn Health-Tech, Professor Brian Litt is working closely with me to facilitate all the rapid response team initiatives, and in helping to garner support the center and remove obstacles. These projects include ramping up ventilator capacity and fabrication of ventilator parts, the creation of point-of-care ultrasounds and diagnostic testing, evaluating processes of PPE decontamination, and more. Visit the Penn Health-Tech coronavirus website to learn more, get involved with an existing team, or submit a new idea.

BE Labs COVID-19 Efforts

BE Educational Labs Director Sevile Mannickarottu & Staff

BE Educational Labs staff members Dana Abulez (BE ’19, Master’s BE ’20) and Matthew Zwimpfer (MSE ’18, Master’s MSE ’19) take shifts to laser-cut face shields.

The George H. Stephenson Foundation Educational Laboratory & Bio-MakerSpace staff have donated their PPE to Penn Medicine. Two staff members (Dana Abulez, BE ’19, Master’s BE ’20 and Matthew Zwimpfer, MSE ’18, Master’s MSE ’19) took shifts to laser-cut face shields in collaboration with Penn Health-Tech. Dana and Matthew are also working with Dr. Matthew Maltese on his low-cost ventilator project (details below).

Low-Cost Ventilator

Matthew Maltese, Adjunct Professor of Medical Devices and BE Graduate Group Member

Children’s Hospital of Philadelphia Center for Injury Research and Prevention (CIRP)

Dr. Maltese is rapidly developing a low-cost ventilator that could be deployed in Penn Medicine for the expected surge, and any surge in subsequent waves. This design is currently under consideration by the FDA for Emergency Use Authorization (EUA). This example is one of several designs considered by Penn Medicine in dealing with the patient surge.

Face Shields

David F. Meaney, Solomon R. Pollack Professor of Bioengineering and Senior Associate Dean

Molecular Neuroengineering Lab

Led by David Meaney, Kevin Turner, Peter Bruno and Mark Yim, the face shield team at Penn Health-Tech is working on developing thousands of rapidly producible shields to protect and prolong the usage of Personal Protective Equipment (PPE). Learn more about Penn Health-Tech’s initiatives and apply to get involved here.

Update 4/29/20: The Penn Engineering community has sprung into action over the course of the past few weeks in response to COVID-19. Dr. Meaney shared his perspective on those efforts and the ones that will come online as the pandemic continues to unfold. Read the full post on the Penn Engineering blog.

OUTREACH & EDUCATION

Student Community Building

Yale Cohen, Professor of Otorhinolaryngology, Department of Psychology, BE Graduate Group Member, and BE Graduate Chair

Auditory Research Laboratory

Yale Cohen, and Penn Bioengineering’s Graduate Chair, is working with Penn faculty and peer institutions across the country to identify intellectually engaging and/or community-building activities for Bioengineering students. While those ideas are in progress, he has also worked with BE Department Chair Ravi Radhakrishnan and Undergraduate Chair Andrew Tsourkas to set up a dedicated Penn Bioengineering slack channel open to all Penn Bioengineering Undergrads, Master’s and Doctoral Students, and Postdocs as well as faculty and staff. It has already become an enjoyable place for the Penn BE community to connect and share ideas, articles, and funny memes.

Undergraduate Course: Biotechnology, Immunology, Vaccines and COVID-19 (ENGR 35)

Daniel A. Hammer, Alfred G. and Meta A. Ennis Professor of Bioengineering and Chemical and Biomolecular Engineering

The Hammer Lab

This Summer Session II, Professor Dan Hammer and CBE Senior Lecturer Miriam R. Wattenbarger will teach a brand-new course introducing Penn undergraduates to a basic understanding of biological systems, immunology, viruses, and vaccines. This course will start with the fundamentals of biotechnology, and no prior knowledge of biotechnology is necessary. Some chemistry is needed to understand how biological systems work. The course will cover basic concepts in biotechnology, including DNA, RNA, the Central Dogma, proteins, recombinant DNA technology, polymerase chain reaction, DNA sequencing, the functioning of the immune system, acquired vs. innate immunity, viruses (including HIV, influenza, adenovirus, and coronavirus), gene therapy, CRISPR-Cas9 editing, drug discovery, types of pharmaceuticals (including small molecule inhibitors and monoclonal antibodies), vaccines, clinical trials. Some quantitative principles will be used to quantifying the strength of binding, calculate the dynamics of enzymes, writing and solving simple epidemiological models, methods for making and purifying drugs and vaccines. The course will end with specific case study of coronavirus pandemic, types of drugs proposed and their mechanism of action, and vaccine development.
Update 4/29/20: Read the Penn Engineering blog post on this course published April 27, 2020.

Neuromatch Conference

Konrad Kording, Penn Integrates Knowledge University Professor of Bioengineering, Neuroscience, and Computer and Information Science

Kording Lab

Dr. Kording facilitated Neuromatch 2020, a large virtual neurosciences conferences consisting of over 3,000 registrants. All of the conference talk videos are archived on the conference website and Dr. Kording has blogged about what he learned in the course of running a large  conference entirely online. Based on the success of Neuromatch 1.0, the team are now working on planning Neuromatch 2.0, which will take place in May 2020. Dr. Kording is also working on facilitating the transition of neuroscience communication into the online space, including a weekly social (#neurodrinking) with both US and EU versions.

Neuromatch Academy

Konrad Kording, Penn Integrates Knowledge University Professor of Bioengineering, Neuroscience, and Computer and Information Science

Kording Lab

Dr. Kording is working to launch the Neuromatch Academy, an open, online, 3-week intensive tutorial-based computational neuroscience training event (July 13-31, 2020). Participants from undergraduate to professors as well as industry are welcome. The Neuromatch Academy will introduce traditional and emerging computational neuroscience tools, their complementarity, and what they can tell us about the brain. A main focus is not just on using the techniques, but on understanding how they relate to biological questions. The school will be Python-based making use of Google Colab. The Academy will also include professional development / meta-science, model interpretation, and networking sessions. The goal is to give participants the computational background needed to do research in neuroscience. Interested participants can learn more and apply here.

Journal of Biomedical Engineering Call for Review Articles

Beth Winkelstein, Vice Provost for Education and Eduardo D. Glandt President’s Distinguished Professor of Bioengineering

Spine Pain Research Lab

The American Society of Medical Engineers’ (ASME) Journal of Biomechanical Engineering (JBME), of which Dr. Winkelstein is an Editor, has put out a call for review articles by trainees for a special issue of the journal. The call was made in March 2020 when many labs were ramping down, and trainees began refocusing on review articles and remote work. This call continues the JBME’s long history of supporting junior faculty and trainees and promoting their intellectual contributions during challenging times.
Update 4/29/20: CFP for the special 2021 issue here.

Are you a Penn Bioengineering community member involved in a coronavirus-related project? Let us know! Please reach out to ksas@seas.upenn.edu.

 

 

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Danielle Bassett Named AIMBE Fellow

Danielle Bassett, Ph.D.

Danielle Bassett, J. Peter Skirkanich Professor of Bioengineering, has been named an American Institute for Medical and Biological Engineering (AIMBE) Fellow.

Election to the AIMBE College of Fellows is among the highest professional distinctions accorded to a medical and biological engineer. College membership honors those who have made outstanding contributions to “engineering and medicine research, practice, or education” and to “the pioneering of new and developing fields of technology, making major advancements in traditional fields of medical and biological engineering, or developing/implementing innovative approaches to bioengineering education.”

Bassett was nominated, reviewed, and elected by peers and members of the College of Fellows for “significant contributions to the application of neural network theory for understanding both physio and patho-physiological brain function.”

As a result of health concerns, AIMBE’s annual meeting and induction ceremony scheduled for March 29–30, 2020, was cancelled. Under special procedures, Bassett was remotely inducted along with 156 colleagues who make up the AIMBE College of Fellows Class of 2020.

Originally posted on the Penn Engineering blog.

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Machine Learning Reveals New Antibiotics for Resistant Bacteria

Cesar de la Fuente-Nunez, PhD

Once hailed as medical miracles, antibiotics are losing their effectiveness due to the rapid increase of bacterial immunity.

Researchers are scrambling to keep up with evolution, and they are currently exploring how machine learning can be applied to microbiology to develop more effective treatments.

In the past, researchers have studied bacteria behavior and used their findings to work against the natural patterns of bacterial life. In the 1980s, computer-assisted screening methods helped researchers in their efforts but few developments surfaced from their work. It seemed that there were no new antibiotics to be found using traditional methods, and pharmaceutical companies stepped away from funding antibiotic development in favor of more profitable drugs used to treat chronic conditions. But a new field of research shows a way forward, thanks to the massive advances in computing that have occurred over the intervening decades.

Among the pioneering researchers in this field is César de La Fuente, Presidential Assistant Professor in Psychiatry, Microbiology and Bioengineering. De La Fuente is accelerating the discovery of new antibiotics with his Drug Repurposing Hub, a library of more than 6,000 compounds that is using machine learning algorithms to seek out possible solutions for human disease. With his compound library, de La Fuente is able to examine drugs already approved by the FDA and hunt for new, more effective applications.

In addition to this work, de La Fuente and his colleagues are interested in using machine learning to innovate drug design itself. His lab uses a machine learning platform to generate new molecules in silico and perform experiments on them. Once the results of the experiments come in, they are fed back into the computer so the machine learning platform can continuously learn and improve its findings from the data.

In a recent interview with Katherine Harmon Courage in Quanta Magazine, de La Fuente said:

“The hypothesis is that nature has run out of inspiration in terms of providing us with new antibiotics. That’s why we think that machines … could diversify natural molecules to convert them to synthetic versions that would be much more effective.”

Originally posted on the Penn Engineering blog. Read more about de La Fuente’s work and other researchers exploring the computational design of new antibiotics in Quanta Magazine or The Atlantic.

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Five Tips to Stay Positive and Healthy During Social Isolation

Though the coronavirus situation is changing daily, even hourly, by now the need for physical separation from those not in your household is clear. That doesn’t mean it’s easy, says Penn psychologist Melissa Hunt.

“We’re social animals,” says Hunt, associate director of clinical training in Penn’s Psychology Department. “We have an entire neuroendocrine system that responds to touch and social proximity with people we care about, that contributes to our sense of well-being and connection in the world. Losing out on that is really hard.”

It’s also not something we’ve really been asked to do before, says Lyle Ungar, a Penn computer scientist who is part of the World Well-Being Project, an initiative that uses social media language to measure psychological well-being and physical health. “This is an experiment on a scale that we’ve never seen in the United States,” he says.

Ungar and Hunt offer some suggestions to stay positive and healthy in the face of this new social isolation.

1. Maintain a connection with the people you love, even if it can’t be a physical one. 

“Social distance does not mean no social contact,” Ungar says. Psychologically, face-to-face conversations are best, but right now they’re not likely possible. Instead, Ungar suggests video calls. “They’re second best in terms of emotional bonding,” he says. “Phone calls aren’t as good as video chats, and texting is even worse. But of course, being totally isolated is the worst.”

Read the full five tips at Penn Today. Media contact Michele W. Berger.

Melissa G. Hunt is the associate director of clinical training in the Department of Psychology in the School of Arts and Sciences at the University of Pennsylvania. 

Lyle Ungar is a professor in the departments of Bioengineering and Computer and Information Science in the School of Engineering and Applied Science, in the Graduate Group in Genomics and Computational Biology in the Perelman School of Medicine, in the Department of Operations, Information, and Decisions in the Wharton School, and in the Department of Psychology in the School of Arts and Sciences.

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Penn is fighting pancreatic cancer

A microscopic view of pancreatic adenocarcinoma. (Image: Emma Furth)

Swept up in a pancreatic cancer diagnosis is inevitably a sense of fear and sadness.

But at Penn, researchers are bringing new hope to this disease. And with patients like Nick Pifani, it’s clear that they’re moving in the right direction.

Pifani, from Delran, New Jersey, first noticed some lingering stomach upset in February 2017. He called his family doctor, concerned—especially given that he was an otherwise healthy marathon runner who was only 42. He was sent to a gastrointestinal specialist. A few weeks later, some crippling stomach pain sent him back to the emergency room and he received an MRI that showed a mass on his pancreas—Stage Three, inoperable, he was told.

He was treated with chemotherapy, along with radiation and, eventually, and after receiving advice from doctors at Penn, his tumor was removed. Thereafter, he realized he had a PALB2 mutation—a cousin of the BRCA gene mutation. At that moment, his long-term needs changed and he found himself seeking specialized care at Penn, where he met Kim Reiss Binder, assistant professor of medicine at the Hospital of the University of Pennsylvania (HUP).

“I’m a planner; I want to understand what [my] potential options are,” Pifani says. “[Reiss Binder] asked why I was there to see her and I explained and quickly I could tell she was—outside of her being remarkably intelligent—a great listener and a compassionate doctor.”

“I have a feeling she worries about me more than I do,” he laughs.

Pifani has now been in remission for two years and four months; he sees Reiss-Binder every three months for checkups. His survival story is inspiring and a sign of momentum, even if a world without pancreatic cancer is still frustratingly out of reach.

Pancreatic cancer at Penn

Pancreatic cancer is the third-leading cause of cancer-related death in the United States, outmatched only by lung cancer (No. 1) and colorectal cancer (No. 2). A person diagnosed with pancreatic cancer is still unlikely to survive past five years—only 9% of survivors do, giving it the highest mortality rate among every major cancer.

In short, pancreatic cancer seldom paves the way for optimistic narratives. Some of the hope that has surfaced, though, is thanks to some talent, dedication to the cause, and hard work at Penn.

A key point of progress in the battle against the disease was made in 2002, when former Assistant Professor of Medicine David Tuveson established a standard model for examining human development of this disease in mice. This model has allowed for a reliable way to study the disease and has influenced progress made here at Penn and elsewhere since.

“There’s been a burst of activity in translational research, from bench to bedside,” explains Ben Stanger, the Hanna Wise Professor in cancer research and director of the Penn Pancreatic Cancer Research Center (PCRC) at the Abramson Cancer Center.

“And there’s a lot of momentum with community building, a dramatic increase in patient volumes, and a dramatic increase in what we know about the cancer,” he says of the status of pancreatic cancer today.

Reiss Binder, meanwhile, explains that one mark of progress at Penn and beyond has been learning about people like Pifani, who have the PALB2 gene, and why they respond differently to treatments than those without it. Platinum-based chemotherapies, for example, are especially effective for people with the PALB2 gene who are battling pancreatic cancer. An ongoing trial at Penn has tested and found some success with using PARP inhibitors—taken orally as an enzyme that fixes single-stranded breaks of DNA—as a maintenance therapy in that same PALB2 demographic after they’ve had chemotherapy. These are less toxic than chemotherapy for patients with the same mutations.

It’s all been slow progress toward better treatments, but there has been progress.

“This is the tip of the iceberg for a disease that we historically have treated with perpetual chemotherapy,” Reiss Binder says. “We owe it to patients to find better options to suppress the cancer but not ruin their quality of life.”

Catching cancer earlier

The consensus on why pancreatic cancer is so deadly? It just can’t be spotted fast enough.

Pancreatic cancer often presents well after it has developed and metastasized, and does so in a way that is not easy to recognize as cancer. Common symptoms include, for example, stomach upset and back pain. And by the time a harder-to-ignore symptom of the cancer surfaces, a sort of yellowing of the skin (a result of a bile duct blockage), it’s likely too late to stop the cancer in its tracks.

One approach to improved detection being tested at Penn, by Research Assistant Professor of Medicine Erica Carpenter, is a liquid biopsy—drawn from a standard blood test. Current means to test for pancreatic cancer—imaging through an endoscopic tube—are invasive and expensive, meaning a common liquid test could transform how many cases are detected early.

Carpenter explains that circulating tumor cells (CTCs) can shed from a tumor that’s adjacent to the wall of a blood vessel; what’s shed then shows up in a blood test. The cells, if detected, can explain more about the nature of the tumor, giving doctors an opportunity to examine characteristics of cancerous cells and decide how to effectively treat a tumor if it can’t be surgically removed. It also allows interpretations of disease burden and the effectiveness of medications—through genome sequencing—that imaging does not.

Ultimately, this gives doctors the potential to track the growth of a tumor before it’s fully developed, all through one tube of blood—detected through an innovative use of technology.

 

David Issadore, Ph.D.

David Issadore, associate professor of bioengineering and electrical and systems engineering in the School of Engineering and Applied Science, has worked since 2017 to develop a chip that detects cancer in the blood, using machine learning to sort through literally hundreds of billions of vesicles and cells, looking for these CTCs. The chip retrieves data and the machine learning developed interprets that data, attempting to make a diagnosis that not only finds pancreatic cancer but also provides information about its progression—and, importantly, whether a patient might benefit from surgery.

Read the full story at Penn Today. Media contact Brandon Baker.

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The Optical Society Names Nader Engheta the 2020 Max Born Award Recipient

Nader Engheta, Ph.D.

The Optical Society (OSA) has named Nader Engheta, H. Nedwill Ramsey Professor in the Department of Electrical and Systems Engineering, as the 2020 recipient of the Max Born Award.

Engheta, who also has appointments in the departments of Bioengineering and Materials Science and Engineering, is honored for pioneering contributions to optical metamaterials and nanoscale optics.

“The Born Award recognizes Nader Engheta’s exceptional contributions to the fields of metamaterials, transformation optics and nanophotonics,” said 2020 OSA President Stephen D. Fantone, founder and president of Optikos Corporation. “This honor is emblematic of the pioneering work he has done in near-zero index metamaterials.”

Read the full story on the Penn Engineering blog.

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Listen: Danielle Bassett Uses Network Science to Find Links in Human Curiosity

Danielle Bassett, Ph.D.

Danielle Bassett, J. Peter Skirkanich Professor of Bioengineering and Electrical and Systems Engineering, is a curious scientist.

Featured on a recent episode of “Choosing to be Curious” on WERA 96.7 Radio Arlington, Bassett discussed her work in studying curiosity and the potential neural mechanisms behind it. In her work, Bassett strives to re-conceptualize curiosity itself, defining it as not just seeking new bits information, but striving to understand the path through which those bits are connected.

Bassett is a pioneering researcher in the field of network science and how its tools can be applied to understand the brain. Now, Bassett and her research team are using the tools of network science and complex systems theory to uncover what common styles of curiosity people share and how individual styles differ. In addition, the team is exploring if there are canonical types of curiosity among humans or if each person’s curiosity architecture is unique.

This isn’t the first time Bassett has combined the tools of disparate fields to pursue her research. For as long as she can remember, Bassett has been insatiably curious and, while she was homeschooled as a child, she often wandered from one subject to the next and let her own interest guide her path. For Bassett, studying curiosity with the tools of physical, biology, and engineering is a natural step in her research journey.

In her interview with host Lynn Borton, Bassett says:

“What took me to curiosity is the observation that there’s a problem in defining the ways in which we search for knowledge. And that perhaps the understanding of curiosity could be benefitted by a scientific and mathematical approach. And that maybe the tools and conceptions that we have in mathematics and physics and other areas of science are useful for understanding curiosity. Which most people would consider to be more in the world of the humanities than the sciences….“Part of what I’m hoping to do is to illustrate that there are connections between disciplines that seem completely separate. Sometimes some of the best ideas in science are inspired not by a scientific result but by something else.”

To hear more about Bassett’s research on curiosity, listen to the full episode of Choosing to Be Curious.

Originally posted on the Penn Engineering blog.

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Getting Physical with Developmental Biology Research

macrophages Discher
Dennis Discher, Ph.D.

By Izzy Lopez

While genetics and biochemistry research has dominated the conversation about how human bodies are formed, new research — with an old twist — is proposing that there is another star in the show of human development: mechanical forces.

At the turn of the twentieth century, medical research relied on simple mechanics to explain scientific phenomena, including how human cells morph into shape from embryo to newborn and beyond. As better chemistry techniques and DNA research burst onto the scene, however, the idea that cells could be affected by physical forces took a back seat. Now researchers are referring back to this vintage idea and bringing it into the 21st century.

Dennis Discher, Robert D. Bent Professor in the Departments of Chemical and Biomolecular Engineering, Bioengineering and Mechanical Engineering and Applied Mechanics, was featured in a recent article in Knowable Magazine for his research on the human heart and how mechanical forces exerted on heart cells give the vital organ its necessary stiffness during development.

Read the full story on the Penn Engineering blog.

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Dr. Danielle Bassett and Dr. Jason Burdick Named to Highly Cited Researchers List

by Sophie Burkholder

One way to measure the success or influence of a researcher is to consider how many times they’re cited by other researchers. Every published paper requires a reference section listing relevant earlier papers, and the Web of Science Group keeps track of how many times different authors are cited over the course of a year.

Danielle Bassett, Ph.D.

In 2019, two members of the Penn Bioengineering department, Jason Burdick, Ph.D., and Danielle Bassett, Ph.D., were named Highly Cited Researchers, indicating that each of them placed within the top 1% of citations in their field based on the Web of Science’s index. For the past year, only 6,300 researchers were recognized with this honor, a number that makes up a mere 0.1% of researchers worldwide. Bassett’s lab looks at the use of knowledge, brain, and dynamic networks to understand bioengineering problems at a systems-level analysis, while Burdick’s lab focuses on advancements in tissue engineering through polymer design and development.

Robert D. Bent Chair
Jason Burdick, PhD

Burdick’s and Bassett’s naming to the list of Highly Cited Researchers demonstrates that their research had an outsized influence over current work in the field of bioengineering in the last year, and that new innovations continue to be developed from foundations these two Penn researchers created. To be included among such a small percentage of researchers worldwide indicates that Bassett and Burdick are sources of great impact and influence in bioengineering advancements today.

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Computer-generated Antibiotics, Biosensor Band-Aids, and the Quest to Beat Antibiotic Resistance

By Michele W. Berger

Imagine if a computer could learn from molecules found in nature and use an algorithm to generate new ones. Then imagine those molecules could get printed and tested in a lab against some of the nastiest, most dangerous bacteria out there — bacteria quickly becoming resistant to our current antibiotic options.

Or consider a bandage that can sense an infection with fewer than 100 bacterial cells present in an open wound. What if that bandage could then send a signal to your phone letting you know an infection had started and asking you to press a button to trigger the release of the treatment therapy it contained?

These ideas aren’t science fiction. They’re projects happening right now, in various stages, in the lab of synthetic biologist , who joined the University as a Presidential Professor in May 2019. His ultimate goal is to develop the first computer-made antibiotics. But beyond that, his lab — which includes three postdoctoral fellows, a visiting professor, and a handful of graduate students and undergrads — has many other endeavors that sit squarely at the intersection of computer science and microbiology.

Computer-generated antibiotics

Antibiotic resistance is becoming a dangerous problem, both in the United States and worldwide. According to the , each year in the U.S., at least 2.8 million people get infections that antibiotics can’t help, and more than 35,000 die from those infections. Around the world, common ailments like pneumonia and food-borne illness are getting harder to treat.

De la Fuente poses near Penn’s “Biopond”
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 does today.

New antibiotics are needed, and according to de la Fuente, it’s time to look beyond the traditional approach.

“We’ve relied on nature as a source of antibiotics for many, many years. My whole hypothesis is that nature has perhaps run out of inspiration,” says de la Fuente, who has appointments in the and the . “We haven’t been able to discover any new scaffolds for many years. Can we digitize that information, nature’s chemistry, to be able to create and discover new molecules?”

To do that, his team turned to amino acids, the building blocks of protein molecules. The 20 that occur naturally bond in countless sequences and lengths, then fold to form different proteins. The sequencing possibilities are expansive, more than the number of stars in the universe. “We could never synthesize all of them and just see what happens,” says postdoc Marcelo Melo. “We have to combine the chemical knowledge — decades of chemistry on these tell us how they behave — with the computational side, because a computer can find patterns unlike any human could.”

Using machine learning, the researchers provide the computer with natural molecules that successfully work against bacteria. The computer learns from those examples, then generates new, artificial molecules. “We try this back and forth and hopefully we find patterns, new patterns that we can explore, instead of blindly searching,” Melo says.

The computer can then test each artificial sequence virtually, setting aside the most successful components and tossing the rest, in a form of computational natural selection. Those pieces with the highest potential get used to create new sequences, theoretically producing better and better ones each time.

De la Fuente’s team has seen some promising results already: “A lot of the molecules we’ve synthesized have worked,” he says. “The best ones worked in animal models. They were able to reduce infections in mice — which was pretty cool, given that the computer generated the whole thing.” Still, de la Fuente says the work is years away from producing anything close to a shelf-ready antibiotic.

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