We wanted you to know that we in BE fully stand behind and reiterate the message from President Gutmann in full support of our Black students, postdocs, staff, colleagues, and friends.
As noted by President Gutmann, we all are feeling outrage, anger, grief, and myriad other emotions. We are at a loss to comprehend and to process the magnitude and implications of the brutality, oppression, and injustice that have come to light once again following the horrific event of George Floyd’s murder.
Several students and colleagues have reached out expressing their desires to contribute actively to effect a positive and progressive change. Our President Gutmann and Provost Pritchett have summarized some of the Penn initiatives towards our local communities in their message linked above. Numerous others are proactively contributing large and small. While we may not agree on many things, we can all agree that a lot remains to be done, and it will take time and sustained effort and commitment on our part. We are committed to the cause: to effect continual and progressive change for nurturing equality and cultural sensitivity as we build a diverse academic ecosystem, and this includes BE, Penn, and our surrounding community. It is our commitment to our Black friends and colleagues.
We take this opportunity to share this article sent by Denise Lay: Answering the Question, ‘What Can I Do?’ and this document compiled by BE Ph.D. student Lasya Sreepada created to share resources and opportunities for members of the University of Pennsylvania community to help their local communities.
Also, here are a few resources to help cope:
Racial Justice and Equity (from Bucketlisters): A listing of resources, organizations and actions, including Philadelphia specific organizations.
Mostly and immediately, we write this note to reiterate that we stand with and support our Black students, postdocs, staff, colleagues, and friends in this difficult period.
Researchers develop a new model for how the brain processes complex information: by striking a balance between accuracy and simplicity while making mistakes along the way.
By Erica K. Brockmeier
The human brain is a highly advanced information processor composed of more than 86 billion neurons. Humans are adept at recognizing patterns from complex networks, such as languages, without any formal instruction. Previously, cognitive scientists tried to explain this ability by depicting the brain as a highly optimized computer, but there is now discussion among neuroscientists that this model might not accurately reflect how the brain works.
Now, Penn researchers have developed a different model for how the brain interprets patterns from complex networks. Published in Nature Communications, this new model shows that the ability to detect patterns stems in part from the brain’s goal to represent things in the simplest way possible. Their model depicts the brain as constantly balancing accuracy with simplicity when making decisions. The work was conducted by physics Ph.D. student Christopher Lynn, neuroscience Ph.D. student Ari Kahn, and Danielle Bassett, J. Peter Skirkanich Professor in the departments of Bioengineering and Electrical and Systems Engineering.
This new model is built upon the idea that people make mistakes while trying to make sense of patterns, and these errors are essential to get a glimpse of the bigger picture. “If you look at a pointillist painting up close, you can correctly identify every dot. If you step back 20 feet, the details get fuzzy, but you’ll gain a better sense of the overall structure,” says Lynn.
To test their hypothesis, the researchers ran a set of experiments similar to a previous study by Kahn. That study found that when participants were shown repeating elements in a sequence, such as A-B-C-B, etc., they were automatically sensitive to certain patterns without being explicitly aware that the patterns existed. “If you experience a sequence of information, such as listening to speech, you can pick up on certain statistics between elements without being aware of what those statistics are,” says Kahn.
To understand how the brain automatically understands such complex associations within sequences, 360 study participants were shown a computer screen with five gray squares corresponding to five keys on a keyboard. As two of the five squares changed from gray to red, the participants had to strike the computer keys that corresponded to the changing squares. For the participants, the pattern of color-changing squares was random, but the sequences were actually generated using two kinds of networks.
The researchers found that the structure of the network impacted how quickly the participants could respond to the stimuli, an indication of their expectations of the underlying patterns. Responses were quicker when participants were shown sequences that were generated using a modular network compared to sequences coming from a lattice network.
In a Q&A, researcher Lyle Ungar discusses why counties that frequently use words like ‘love’ aren’t necessarily happier, plus how techniques from this work led to a real-time COVID-19 wellness map.
By Michele W. Berger
People in different areas across the United States reacted differently to the threat of COVID-19. Some imposed strict restrictions, closing down most businesses deemed nonessential; others remained partially open.
Such regional distinctions are relatively easy to quantify, with their effects generally understandable through the lens of economic health. What’s harder to grasp is the emotional satisfaction and happiness specific to each place, a notion Penn’s World Well-Being Project has been working on for more than five years.
In 2017, the group published the WWBP Map, a free, interactive tool that displays characteristics of well-being by county based on Census data and billions of tweets. Recently, WWBP partnered with Penn Medicine’s Center for Digital Health to create a COVID map, which reveals in real time how people across the country perceive COVID-19 and how it’s affecting their mental health.
That map falls squarely in line with a paper published this week in the Proceedings of the National Academy of Sciences by computer scientist Lyle Ungar, one of the principal investigators of the World Well-Being Project, and colleagues from Stanford University, Stony Brook University, the National University of Singapore, and the University of Melbourne.
By analyzing 1.5 billion tweets and controlling for common words like “love” or “good,” which frequently get used to connote a missing aspect of someone’s life rather than a part that’s fulfilled, the researchers found they could discern subjective well-being at the county level. “We have a long history of collecting people’s language and asking people who are happier or sadder what words they use on Facebook and on Twitter,” Ungar says. “Those are mostly individual-level models. Here, we’re looking at community-level models.”
In a conversation with Penn Today, Ungar describes the latest work, plus how it’s useful in the time of COVID-19 and social distancing.
KIChE is an organization that aims “to promote constructive and mutually beneficial interactions among Korean Chemical Engineers in the U.S. and facilitate international collaboration between engineers in the U.S. and Korea.”
David F. Meaney, the Senior Associate Dean of Penn Engineering and Solomon R. Pollack Professor of Bioengineering, is known for his scholarship and innovation in neuroengineering and concussion science, his leadership as former Chair of the Department of Bioengineering, and for his marshaling of interdisciplinary research between Penn Engineering and the University’s health schools.
The Penn Engineering community has sprung into action over the course of the past few weeks in response to COVID-19. Meaney shared his perspective on those efforts and the ones that will come online as the pandemic continues to unfold.
And then our campus — and world — changed.
COVID-19 is among us, in ways that we can’t exactly measure. It is among us in ways that we feel — we probably know someone that has tested positive for the virus, and others that are living with someone that is sick. And we all realize the virus will be with us for some time; the exact amount we don’t know.
Which brings up the question — what can we do to fight this pandemic? Many of us are trying to find ways to keep our connections with others vibrant and strong in the world of Zoom, Hangout, and BlueJeans. That is important. Let me also say that I can’t wait to reconnect with everyone in person, and close my laptop for a week.
But staying connected is what everyone should do. I often think about what can engineers do?
As the Senior Associate Dean, I want to let you know what I’m seeing on a quiet, but not shuttered, Penn campus. Examples of our response to the pandemic include our faculty designing personal protective equipment for health care workers, and our students, faculty and staff volunteering to assemble it. Other faculty are inventing COVID-19 test kits that can be completed at home, with the results available in less than an hour. Professors are sharing their creative mask designs with the world, for free, to make sure that we can all feel comfortable walking outside. And yet others that are collaborating to make a vaccine that will help us put COVID-19 behind us, permanently.
All of this is happening at speeds we have never seen before. Ideas move to prototypes and testing in days, not months, and to product in a week. We are not alone — our colleagues across campus are working at light speed to generate better tests, treatments, and models to fight COVID-19. This time, Nature has given us the problem. Time for us to solve it.
Transmission electron micrograph of multiple bacteriophages, viruses that infect bacteria, attached to a cell wall. New research describes how bacteria can optimize their “memory” of past viral infections in order to launch an effective immune response against a new invader. (Image: Graham Beards)
Before CRISPR became a household name as a tool for gene editing, researchers had been studying this unique family of DNA sequences and its role in the bacterial immune response to viruses. The region of the bacterial genome known as the CRISPR cassette contains pieces of viral genomes, a genomic “memory” of previous infections. But what was surprising to researchers is that rather than storing remnants of every single virus encountered, bacteria only keep a small portion of what they could hold within their relatively large genomes.
In recent years, CRISPR has become the go-to biotechnology platform, with the potential to transform medicine and bioengineering. In bacteria, CRISPR is a heritable and adaptive immune system that allows cells to fight viral infections: As bacteria come into contact with viruses, they acquire chunks of viral DNA called spacers that are incorporated into the bacteria’s genome. When the bacteria are attacked by a new virus, spacers are copied from the genome and linked onto molecular machines known as Cas proteins. If the attached sequence matches that of the viral invader, the Cas proteins will destroy the virus.
Bacteria have a different type of immune system than vertebrates, explains senior author Vijay Balasubramanian, but studying bacteria is an opportunity for researchers to learn more about the fundamentals of adaptive immunity. “Bacteria are simpler, so if you want to understand the logic of immune systems, the way to do that would be in bacteria,” he says. “We may be able to understand the statistical principles of effective immunity within the broader question of how to organize an immune system.”
This research was supported by the Simons Foundation (Grant 400425) and National Science Foundation Center for the Physics of Biological Function (Grant PHY-1734030).
Hammer will offer a course on COVID-19 and the coronavirus pandemic during Penn’s Summer II session, which will be held online this year. The course will be co-taught with Miriam Wattenbarger, senior lecturer in CBE.
The course, “Biotechnology, Immunology, and COVID-19,” will culminate with a case study of the coronavirus pandemic including the types of drugs proposed and their mechanism of action, as well as the process of vaccine development.
“Obviously, the pandemic has been a life-altering event, causing an immense dislocation for everyone in our community, especially the students. Between me and Miriam, who has been trumpeting the importance of vaccines for some time in her graduate-level CBE courses, we have the expertise to inform students about this disease and how we might combat it,” says Hammer.
For more than ten years, Wattenbarger has run courses and labs focused on drug delivery and biotechnology, key elements of the vaccine development process.
“I invite both researchers and industry speakers to meet with my students,” Wattenbarger says, “so that they learn the crucial role engineers play in both vaccine development and manufacturing.”
Beyond studying the interactions between the immune system and viruses — including HIV, influenza, adenovirus and coronavirus — students will cover a variety of biotechnological techniques relevant to tracking and defending against them, including recombinant DNA technology, polymerase chain reaction, DNA sequencing, gene therapy, CRISPR-Cas9 editing, drug discovery, small molecule inhibitors, vaccines and the clinical trial process.
Students will also learn the mathematical principles used to quantify biomolecular interactions, as well as those found behind simple epidemiological models and methods for making and purifying drugs and vaccines.
“We all have to contribute in the ways that we can. Having taught biotechnology to freshmen for the past decade, this is something that I can do that can both inform and build community,” says Hammer. “Never has it been more important to have an informed and scientifically literate community that can fight this or any future pandemic.”
A blood test may be able to detect the most common form of pancreatic cancer while it is still in its early stages while also helping doctors accurately stage a patient’s disease and guide them to the appropriate treatment. A multidisciplinary study found the test—known as a liquid biopsy—was more accurate at detecting disease in a blinded study than any other known biomarker alone, and was also more accurate at staging disease than imaging is capable of alone. The team, which includes researchers from the Perelman School of Medicine, the Abramson Cancer Center, and the School of Engineering and Applied Science, published their findings in Clinical Cancer Research, a journal of the American Association for Cancer Research.
Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is the third leading cause of cancer deaths. The overall five-year survival rate is just 9%, and most patients live less than one year following their diagnosis. One of the biggest challenges is catching the disease before it has progressed or spread. If the disease is caught early, patients may be candidates for surgery to remove the cancer, which can be curative. For locally advanced patients—meaning patients whose cancer has not spread beyond the pancreas but who are not candidates for surgery based on the size or location of the tumor—treatment involves three months of systemic therapy like chemo or radiation, then reassessing to see if surgery is an option. For patients whose disease has spread, there are currently no curative treatment options.
“Right now, the majority of patients who are diagnosed already have metastatic disease, so there is a critical need for a test that can not only detect the disease earlier but also accurately tell us who might be at a point where we can direct them to a potentially curative treatment,” says the study’s co-senior author Erica L. Carpenter,director of the Liquid Biopsy Laboratory and a research assistant professor of medicine. The study’s other co-senior author is David Issadore, an associate professor of bioengineering and electrical and systems engineering.
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
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
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
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
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
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 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
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
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
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
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
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
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
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.
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.