Getting a complex protein like an antibody through the membrane of a cell without damaging either is a long-standing challenge in the life sciences. Penn Engineers have found a plug-and-play solution that makes antibodies compatible with the delivery vehicles commonly used to ferry nucleic acids across that barrier.
For almost any conceivable protein, corresponding antibodies can be developed to block it from binding or changing shape, which ultimately prevents it from carrying out its normal function. As such, scientists have looked to antibodies as a way of shutting down proteins inside cells for decades, but there is still no consistent way to get them past the cell membrane in meaningful numbers.
Now, Penn Engineering researchers have figured out a way for antibodies to hitch a ride with transfection agents, positively charged bubbles of fat that biologists routinely use to transport DNA and RNA into cells. These delivery vehicles only accept cargo with a highly negative charge, a quality that nucleic acids have but antibodies lack. By designing a negatively charged amino acid chain that can be attached to any antibody without disrupting its function, they have made antibodies broadly compatible with common transfection agents.
Beyond the technique’s usefulness towards studying intracellular dynamics, the researchers conducted functional experiments with antibodies that highlight the technique’s potential for therapeutic applications. One antibody blocked a protein that decreases the efficacy of certain drugs by prematurely ejecting them from cells. Another blocked a protein involved in the transcription process, which could be an even more fundamental way of knocking out proteins with unwanted effects.
The researchers’ experiments involved making synthetic tissues with artificial “cells.” The fibrin network that surrounds these beads pull on them when compressed; by changing the number of beads in their experimental tissues, the researchers could suss out how cell-fiber interplay contributes to the tissue’s overall properties.
Tissue gets stiffer when it’s compressed. That property can become even more pronounced with injury or disease, which is why doctors palpate tissue as part of a diagnosis, such as when they check for lumps in a cancer screening. That stiffening response is a long-standing biomedical paradox, however: tissue consists of cells within a complex network of fibers, and common sense dictates that when you push the ends of a string together, it loosens tension, rather than increasing it.
Now, in a study published in Nature, University of Pennsylvania’s School of Engineering and Applied Science researchers have solved this mystery by better understanding the mechanical interplay between that fiber network and the cells it contains.
The researchers found that when tissue is compressed, the cells inside expand laterally, pulling on attached fibers and putting more overall tension on the network. Targeting the proteins that connect cells to the surrounding fiber network might therefore be the optimal way of reducing overall tissue stiffness, a goal in medical treatments for everything from cancer to obesity.
Paul Janmey and Vivek Shenoy
The study was led by Paul Janmey, Professor in the Perelman School of Medicine’s Department of Physiology and in Penn Engineering’s Department of Bioengineering, and Vivek Shenoy, Eduardo D. Glandt President’s Distinguished Professor in Penn Engineering’s Department of Materials Science and Engineering, Mechanical Engineering and Applied Mechanics, and Bioengineering, along with Anne van Oosten and Xingyu Chen, graduate students in Janmey’s and Shenoy’s labs. Van Oosten is now a postdoctoral fellow at Leiden University in The Netherlands.
Shenoy is Director of Penn’s Center for Engineering Mechanobiology, which studies how physical forces influence the behavior of biological systems; Janmey is the co-director of one of the Center’s working groups, organized around the question, “How do cells adapt to and change their mechanical environment?”
Together, they have been interested in solving the paradox surrounding tissue stiffness.
The blue circle is the global symbol for diabetes. Wikimedia Commons.
Diabetes is one of the more common diseases among Americans today, with the American Diabetes Association estimating that approximately 9.5 percent of the population battles the condition today. Though symptoms and causes may vary across types and patients, diabetes generally results from the body’s inability to produce enough insulin to keep blood sugar levels in check. A new experimental treatment from the lab of Sha Jin, Ph.D., a biomedical engineering professor at Binghamton University, aims to use about $1.2 million in recent federal grants to develop a method for pancreatic islet cell transplantation, as those are the cells responsible for producing insulin.
But the catch to this new approach is that relying on healthy donors of these islet cells won’t easily meet the vast need for them in diabetic patients. Sha Jin wants to use her grants to consider the molecular mechanisms that can lead pluripotent stem cells to become islet-like organoids. Because pluripotent stem cells have the capability to evolve into nearly any kind of cell in the human body, the key to Jin’s research is learning how to control their mechanisms and signaling pathways so that they only become islet cells. Jin also wants to improve the eventual culture of these islet cells into three-dimensional scaffolds by finding ways of circulating appropriate levels of oxygen to all parts of the scaffold, particularly those at the center, which are notoriously difficult to accommodate. If successful in her tissue engineering efforts, Jin will not only be able to help diabetic patients, but also open the door to new methods of evolving pluripotent stem cells into mini-organ models for clinical testing of other diseases as well.
A Treatment to Help Others See Better
Permanently crossed eyes, a medical condition called strabismus, affects almost 18 million people in the United States, and is particularly common among children. For a person with strabismus, the eyes don’t line up to look at the same place at the same time, which can cause blurriness, double vision, and eye strain, among other symptoms. Associate professor of bioengineering at George Mason University, Qi Wei, Ph.D., hopes to use almost $2 million in recent funding from the National Institute of Health to treat and diagnose strabismus with a data-driven computer model of the condition. Currently, the most common method of treating strabismus is through surgery on one of the extraocular muscles that contribute to it, but Wei wants her model to eventually offer a noninvasive approach. Using data from patient MRIs, current surgical procedures, and the outcomes of those procedures, Wei hopes to advance and innovate knowledge on treating strabismus.
A Newly Analyzed Brain Mechanism Could be the Key to Stopping Seizures
Among neurological disorders, epilepsy is one of the most common. An umbrella term for a lot of different seizure-inducing conditions, many versions of epilepsy can be treated pharmaceutically. Some, however, are resistant to the drugs used for treatment, and require surgical intervention. Bin He, Ph. D., the Head of the Department of Biomedical Engineering at Carnegie Mellon University, recently published a paper in collaboration with researchers at Mayo Clinic that describes the way that seizures originating at a single point in the brain can be regulated by what he calls “push-pull” dynamics within the brain. This means that the propagation of a seizure through the brain relies on the impact of surrounding tissue. The “pull” he refers to is of the surrounding tissue towards the seizure onset zone, while the “push” is what propagates from the seizure onset zone. Thus, the strength of the “pull” largely dictates whether or not a seizure will spread. He and his lab looked at different speeds of brain rhythms to perform analysis of functional networks for each rhythm band. They found that this “push-pull” mechanism dictated the propagation of seizures in the brain, and suggest future pathways of treatment options for epilepsy focused on this mechanism.
Hyperspectral Imaging Might Provide New Ways of Finding Cancer
A new method of imaging called hyperspectral imaging could help improve the prediction of cancerous cells in tissue specimens. A recent study from a University of Texas Dallas team of researchers led by professor of bioengineering Baowei Fei, Ph.D., found that a combination of hyperspectral imaging and artificial intelligence led to an 80% to 90% level of accuracy in identifying the presence of cancer cells in a sample of 293 tissue specimens from 102 patients. With a $1.6 million grant from the Cancer Prevention and Research Institute of Texas, Fei wants to develop a smart surgical microscope that will help surgeons better detect cancer during surgery.
Fei’s use of hyperspectral imaging allows him to see the unique cellular reflections and absorptions of light across the electromagnetic spectrum, giving each cell its own specific marker and mode of identification. When paired with artificial intelligence algorithms, the microscope Fei has in mind can be trained to specifically recognize cancerous cells based on their hyperspectral imaging patterns. If successful, Fei’s innovations will speed the process of diagnosis, and potentially improve cancer treatments.
People and Places
A group of Penn engineering seniors won the Pioneer Award at the Rothberg Catalyzer Makerthon led be Penn Health-Tech that took place from October 19-20, 2019. SchistoSpot is a senior design project created by students Vishal Tien (BE ‘20), Justin Swirbul (CIS ‘20), Alec Bayliff (BE ‘20), and Bram Bruno (CIS ‘20) in which the group will design a low-cost microscopy dianostic tool that uses computer vision capabilities to automate the diagnosis of schistosomiasis, which is a common parasitic disease. Read about all the winners here.
Virginia Tech University will launch a new Cancer Research Initiative with the hope of creating an intellectual community across engineers, veterinarians, biomedical researchers, and other relevant scientists. The initiative will focus not only on building better connections throughout departments at the university, but also in working with local hospitals like the Carilion Clinic and the Children’s National Hospital in Washington, D.C. Through these new connections, people from all different areas of science and engineering and come together to share ideas.
Associate Professor of Penn Bioengineering Dani Bassett, Ph.D., recently sat down with the Penn Integrates Knowledge University Professor Duncan Watts, Ph.D., for an interview published in Penn Engineering. Bassett discusses the origins of network science, her research in small-world brain networks, academic teamwork, and the pedagogy of science and engineering. You can read the full interview here.
An all-female group of researchers from Northern Illinois University developed a device for use by occupational therapists that can capture three-dimensional images of a patient’s hand, helping to more accurately measure the hand or wrist’s range of motion. The group presented the abstract for their design at this year’s meeting of the Biomedical Engineering Society here in Philadelphia, where Penn students and researchers presented as well.
We would like to congratulate Brit Shields, Ph.D., of the Penn Department of Bioengineering, on her recent promotion to Senior Lecturer. Shields got her start at Penn by completing her Ph.D. here in 2015 in History and Sociology of Science, with a dissertation on scientific diplomacy through the example of Richard Courant and New York University, where Shields completed an M.A. in Humanities and Social Thought: Science Studies. Following the conclusion of her doctorate, Shields immediately joined Penn as a lecturer in the Department of Bioengineering, teaching core undergraduate classes like the Senior Thesis course for B.A.S. degree candidates, and Engineering Ethics, one of the courses that fulfills the ethics requirement for all Penn engineering students. Furthermore, Shields has served as an advisor for undergraduate students on senior thesis in the History and Sociology of Science as well as Bioengineering.
In her new position, Shields will have the chance to further develop the engineering ethics curriculum for SEAS students. She will also take on a direct role with freshman bioengineering students as one of two bioengineering faculty members in charge of advising the incoming classes. Through these opportunities to better connect with students, Shields will be able to continue improving the ethics curriculum for all engineering majors, and increase its efficacy in imparting lessons that all engineers should take to the workforce with them. Beyond her roles in the classroom and as an advisor, Shields will also continue her research in the history and sociology of science and technology focusing on both scientific diplomacy and educational programs for engineers. She says that she “look[s] forward to collaborating with the school’s administration, faculty and students to further develop the engineering ethics curriculum. Being able to innovate in this field with such talented students is incredibly rewarding.”
A Q&A with neuroscientist Konrad Kording on how connections between minds and machines are portrayed in popular culture, and what the future holds for this reality-defying technology.
Science fiction and superhero films portray brain-machine interfaces as malevolent robots that plug into human brains for fuel in The Matrix (top left) or as power-enhancing devices in X-Men (top right). In reality, they can help patients use artificial limbs or directly connect to computers. (Image credits, from top left to bottom right: Warner Brothers, 20th Century Fox, Intelligent Films, AFP Photo/Jean-Pierre Clatot)
For the many superheroes that use high-powered gadgets to save the day, there’s an equal number of villains who use technology nefariously. From robots that plug into human brains for fuel in “The Matrix” to the memory-warping devices seen in “Men in Black,” “Captain Marvel,” and “Total Recall,” technology that can control people’s minds is one of the most terrifying examples of technology gone wrong in science fiction and superhero films.
Now, progress made on brain-machine interfaces, technology that provides a direct communication link between a brain and an external device, is bringing us closer to a world that feels like science fiction. Elon Musk’s company NeuraLink is working on a device to let people control computers with their minds, while Facebook’s “mind-reading initiative” can decode speech from brain activity. Is this progress a glimpse into a dark future, or are there more empowering ways in which brain-machine interfaces could become a force for good?
Q: What are the main challenges in connecting brains to devices?
The key problem is that you need to get a lot of information out of brains. Today’s prosthetic devices are very slow, and if we want to go faster it’s a tradeoff: I can go slower and then I am more precise, or I can go faster and be more noisy. We need to get more data out of brains, and we want to do it electrically, meaning we need to get more electrodes into brains.
So what do you need? You need a way of getting electrodes into the brain without making your brain into a pulp, you want the electrodes to be flexible so they can stay in longer, and then you want the system to be wireless. You don’t want to have a big connector on the top of your head.
It’s primarily a hardware problem. We can get electrodes into brains, but they deteriorate quickly because they are too thick. We can have plugs on people’s heads, but it’s ruling out any real-world usage. All these factors hold us back at the moment.
That’s why the Neuralink announcement was very interesting. They get a rather large number of electrodes into brains using well-engineered approaches that make that possible. What makes the difference is that Neuralink takes the best ideas in all the different domains and puts them together.
Q: Most examples in pop culture of connecting brains to machines have villainous or nefarious ends. Does that match up with how brain-machine interfaces are currently being developed?
Let’s say you’ve had a stroke, you can’t talk, but there’s a prosthetic device that allows you to talk again. Or if you lost your arm, and you get a new one that’s as good as the original—that’s absolutely a force for good.
It’s not a dark, ugly future thing, it’s a beautiful step forward for medicine. I want to make massive progress in these diseases. I want patients who had a stroke to talk again; I want vets to have prosthetic devices that are as good as the real thing. I think short-term this is what’s going to happen, but we are starting to worry about the dark sides.
The annual meeting of the Biomedical Engineering Society (BMES) will be held in our hometown of Philadelphia October 16-19, 2019. The professional society for bioengineers and biomedical engineers will be taking over the city of Brotherly Love, and lots of faculty and students from Penn’s Bioengineering will be attending and presenting their research.
As previously mentioned here, Jason Burdick, Ph.D., the Robert D. Bent Professor of Bioengineering, is one of three chairs of the 2019 annual meeting. He shares this position with two other local faculty: Alisa Morss Clyne, Ph.D., Associate Professor of Mechanical Engineering and Mechanics at Drexel University; and Ruth Ochia, Ph.D., Associate Professor of Instruction in Bioengineering at Temple University. They have worked together since their appointment in 2017 to plan and chair the Philadelphia conference. Check out the video below with details of what to expect from BMES in Philly.
For those of you who have never been to BMES, the event is comprised of a mixture of academic and networking events, including keynote talks from top researchers, thousands of oral and poster presentations, participants from around the world, and social receptions. To plan your itinerary, click here for the program and agenda and here for the schedule at a glance. With the meeting being held locally this year, there are far too many presentations by Penn Bioengineering faculty and staff to list here, so check out BMES’s searchable scientific program or our searchable schedule of Penn faculty student activities at this year’s meeting (separated by day).
In addition to our academic participation, Penn Engineering and Bioengineering are also proud to sponsor this year’s meeting. Registered participants will have several venues to meet and mingle with Penn Engineering faculty, staff, and students and learn about its programs. Staff and volunteers will run a Penn Engineering booth (Booth #824) which will have literature on Penn departments and programs such as the Department of Bioengineering, the Center for Engineering MechanoBiology (CEMB), the Laboratory for Research on the Structure of Matter (LRSM), The Mahoney Institute for Neurosciences (MINS), and the Perelman School of Medicine’s Biomedical Graduate Studies group (BGS) and will be open 9:30am-5:00pm Thursday and Friday, and 9:30am-1:00pm during the conference.
For those interested in social events and networking, check out two back-to-back events on Friday night. From 6:30-8:30 pm, Penn’s Department of Bioengineering, CEMB, and LRSM will host a reception at the Philadelphia Marriott Downtown, Salon E. This will be followed by the meeting’s big BMES Dessert Bash at the Franklin Institute from 8:30-10:30 pm. (Please note: These events are open to registered conference participants only.) For those sticking around, there are no shortage of things to do in Philly, whether you are looking to site-see, shop, or dine.
We hope everyone has a wonderful time at the conference and enjoys Philadelphia! Let us know what activities you are enjoying most by tagging us on Twitter @pennbioeng or Instagram (pennbioengineering) and using the hashtag #pennbioengineering.
We would like to congratulate Dr. Yale Cohen, Ph.D., on his recent appointment as the new Graduate Group Chair for Penn’s Department of Bioengineering. The Graduate Group is a group of faculty that graduate students in bioengineering can choose from to collaborate with on lab research. The Group includes members from nearly all of Penn’s schools, including Penn Engineering, Penn Dental, Penn Medicine, Penn Vet, and the School of Arts and Sciences.
Dr. Cohen specializes in otorhinolaryngology as his primary department, with research areas in computational and experimental neuroengineering. He will take over the role of Graduate Group Chair from Dr. Ravi Radhakrishnan, Ph.D, professor of bioengineering and chemical and biomolecular engineering, whose research specializes in cellular, molecular, and theoretical and computational bioengineering. During his tenure as Graduate Group Chair, Dr. Radhakrishnan says that “the most enjoyable part was the student talks during bioengineering seminars, and the talks at the bioengineering graduate student research symposium,” noting the way they made him realize the “depth and breadth of our graduate group, and how accomplished our students are.”
Also during his time as chair, Dr. Radhakrishnan says he was proud to expand the course BE 699 — the Bioengineering Department’s required seminar for all Ph.D. candidates — to include discussions of leadership and soft-skills, as well as instituting individualized development plans to help students track their work. In looking forward to Dr. Cohen’s appointment to the role, Dr. Radhakrishnan says that he is “a natural and accomplished scientist, educator, and amazing leader who connects so readily and well with our students and faculty.”
Dr. Cohen, looking forward to taking on his new role, says that he hopes to improve programs like the Graduate Association of Bioengineers (GABE) and the mentoring of graduate students so that they can access the wide range of wisdom that comprises the faculty, students, staff, and alumni associated with the Graduate Group. “I am thrilled to be the new chair of the BE Graduate Group and welcome your input and comments on how to improve an already outstanding program,” says Dr. Cohen.
Each week, the National Science Foundation highlights “4 Awesome Discoveries You Probably Didn’t Hear About” — a kid-friendly YouTube series that highlights particularly eye-popping NSF-supported research.
This week, one of those stories was literally about an eye, or rather, a synthetic model of one.
Dan Huh, associate professor in the Department of Bioengineering, and graduate student Jeongyun Seo, recently published a paper that outlined their new blinking eye-on-a-chip. Containing human cells and mechanical parts designed to mimic natural biological functions, including a motorized eyelid, the device was developed as platform for modeling dry eye disease and testing drugs to treat it.
See more of the series at the NSF’s Science360 site, and read more about Huh’s blinking-eye-on-a-chip research here.
The researchers’ model involves mapping the connections between different regions of an individual’s brain while they performed a basic memory task, then using that data to predict how electrical stimulation in one region would affect activity throughout the network. Individuals’ improved performance on the same memory task after stimulation suggests the model could eventually be generalized toward a variety of stimulation therapies.
Brain stimulation, where targeted electrical impulses are directly applied to a patient’s brain, is already an effective therapy for depression, epilepsy, Parkinson’s and other neurological disorders, but many more applications are on the horizon. Clinicians and researchers believe the technique could be used to restore or improve memory and motor function after an injury, for example, but progress is hampered by how difficult it is to predict how the entire brain will respond to stimulation at a given region.
In an effort to better personalize and optimize this type of therapy, researchers from the University of Pennsylvania’s School of Engineering and Applied Science and Perelman School of Medicine, as well as Thomas Jefferson University Hospital and the University of California, Riverside, have developed a way to model how a given patient’s brain activity will change in response to targeted stimulation.
To test the accuracy of their model, they recruited a group of study participants who were undergoing an unrelated treatment for severe epilepsy, and thus had a series of electrodes already implanted in their brains. Using each individual’s brain activity data as inputs for their model, the researchers made predictions about how to best stimulate that participant’s brain to improve their performance on a basic memory test.
The participants’ brain activity before and after stimulation suggest the researchers’ models have meaningful predictive power and offer a first step towards a more generalizable approach to specific stimulation therapies.
Danielle Bassett and Jennifer Stiso.
The study, published in the journal Cell Reports, was led by Danielle Bassett, J. Peter Skirkanich Professor in Penn Engineering’s Department of Bioengineering, and Jennifer Stiso, a neuroscience graduate student in Penn Medicine and a member of Bassett’s Complex Systems Lab.
Penn Engineering is pleased to announce the names of the recipients of four scholarly chairs: Drs. Danielle Bassett, Russell Composto, Boon Thau Loo and Mark Yim. These are all well-deserved honors and we celebrate the privilege of having each of these scholars among us. Two of the recipients, Drs. Bassett and Composto, are members of the Bioengineering Department.
Danielle Bassett has been named the J. Peter Skirkanich Professor of Bioengineering.
Danielle Bassett, Ph.D.
Dr. Bassett is a Professor in the department of Bioengineering at the School of Engineering and Applied Science. She holds a Ph.D. in Physics from the University of Cambridge and completed her postdoctoral training at the University of California, Santa Barbara, before joining Penn in 2013.
Dr. Bassett has received numerous awards for her research, including an Alfred P Sloan Research Fellowship, a MacArthur Fellowship, an Office of Naval Research Young Investigator Award, a National Science Foundation CAREER Award and, most recently, an Erdos-Renyi Prize in Network Science to name but a few. She has authored over 190 peer-reviewed publications as well as numerous book chapters and teaching materials. She is the founding director of the Penn Network Visualization Program, a combined undergraduate art internship and K-12 outreach program bridging network science and the visual arts.
Dr. Bassett’s research is in the area of complex systems and network science, with applications to biological, physical and social networks. She examines dynamic changes in network architecture, the interaction between topological properties of networks, and the influence of network topology on signal propagation and system function. To learn more about Dr. Bassett and her research, please visit her faculty profile.
The J. Peter Skirkanich Professorship was established to honor J. Peter “Pete” Skirkanich, an alumnus, trustee and member of the School of Engineering and Applied Science Board of Overseers who also served as co-chair of Penn Engineering’s “Making History through Innovation” capital campaign and was a member of the University’s “Making History” steering committee. His generous support for Penn Engineering paved the way for Skirkanich Hall.
Russell Composto has been named the Howell Family Faculty Fellow in the School of Engineering and Applied Science.
Russell J. Composto, Ph.D.
Dr. Composto is a Professor in the department of Materials Science and Engineering at the School of Engineering and Applied Science with secondary appointments in Bioengineering and Chemical and Biomolecular Engineering. He joined Penn in 1990 after an appointment as a Research Scientist at Brookhaven National Laboratory and a postdoctoral fellowship at the University of Massachusetts. He is an alumnus of Cornell University, where he received his doctoral degree in 1987.
Dr. Composto is a member of a number of centers and institutes and is the director of Research and Education in Active Coatings Technologies (REACT) for human habitat, a Partnerships for International Research and Education (PIRE) project funded by the National Science Foundation (NSF) and the University of Pennsylvania. Dr. Composto is a previous recipient of the Provost’s Award for Distinguished PhD Teaching and Mentoring. He also serves at the Associate Dean for Undergraduate Education at Penn Engineering.
Dr. Composto’s research is in the area of polymer science and biomolecular engineering. His interests extend to polymer surfaces and interfaces, adhesion and diffusion, and nanocomposite polymer blend and copolymer films. His biomaterials work centers around manipulating the surface of polymers to elicit control over protein adsorption, as well as cell adhesion, orientation, and function, and he has an active research program at the interface of polymer science and biomolecular engineering, which combines block copolymer self-assemble as a basis for orienting stiff biological molecules. To learn more about Dr. Composto and his research, please visit his faculty profile.
The Howell Family Faculty Fellow was established to provide financial support to a faculty member in the School of Engineering and Applied Science. This faculty fellow helped launch the dean’s strategic goal to increase the School’s number of named, endowed faculty positions.
