Neuroscientists frequently say that neural activity ‘represents’ certain phenomena, PIK Professor Konrad Kording and postdoc Ben Baker led a study that took a philosophical approach to tease out what the term means.
Neuroscientists use the word “represent” to encompass multifaceted relationships between brain activity, behavior, and the environment.
One of neuroscience’s greatest challenges is to bridge the gaps between the external environment, the brain’s internal electrical activity, and the abstract workings of behavior and cognition. Many neuroscientists rely on the word “representation” to connect these phenomena: A burst of neural activity in the visual cortex may represent the face of a friend or neurons in the brain’s memory centers may represent a childhood memory.
But with the many complex relationships between mind, brain, and environment, it’s not always clear what neuroscientists mean when they say neural activity “represents” something. Lack of clarity around this concept can lead to miscommunication, flawed conclusions, and unnecessary disagreements.
To tackle this issue, an interdisciplinary paper takes a philosophical approach to delineating the many aspects of the word “representation” in neuroscience. The work, published in Trends in Cognitive Sciences, comes from the lab of Konrad Kording, a Penn Integrates Knowledge University Professor and senior author on the study whose research lies at the intersection of neuroscience and machine learning.
“The term ‘representation’ is probably one of the most common words in all of neuroscience,” says Kording, who has appointments in the Perelman School of Medicine and School of Engineering and Applied Science. “But it might mean something very different from one professor to another.”
Also coauthor on the paper is Benjamin Lansdell, a data scientist in the Department of Developmental Neurobiology at St. Jude Children’s Hospital and former postdoctoral researcher in the Kording lab.
Funding for this study came from the National Institutes of Health (awards 1-R01-EB028162-01 and R01EY021579) and the University of Pennsylvania Office of the Vice Provost for Research.
In these super-resolution images of tendon cell nuclei, the color coding represents chromatin density map, from low density in blue to high density in red. Comparing a healthy human tendon cell nucleus (left) to one diagnosed with tendinosis (right) shows that disease alters the spatial localization and compaction of chromatin.
In a recent study published in Nature Biomedical Engineering, the team detailed what they found when they closely observed the nucleus of cells inside connective tissues deteriorating as a result of tendinosis, which is the chronic condition that results from a tendon repeatedly suffering small injuries that don’t heal correctly. Using the latest super-resolution imaging techniques, they found that the tendon cells involved in maintaining the tissue’s structure in a diseased microenvironment improperly reorder their chromatin — the DNA-containing material that chromosomes are composed of — when attempting to repair.
This and other findings highlighted in the report point to the possibility of new treatments, such as small-molecule therapies, that could restore order to the affected cells.
“Interestingly, we were able to explain the role of mechanical forces on the 3-D organization of chromatin by developing a theory that integrates fundamental thermodynamic principles (physics) with the kinetics of epigenetic regulation (biology),” said study co-author and CEMB Director Vivek Shenoy in a news release from Penn Medicine News.
The CEMB, one of 18 active interdisciplinary research centers funded by the National Science Foundation’s Science and Technology Center (STC) program, brings together dozens of researchers from Penn Engineering and the Perelman School of Medicine, as well as others spread across campus and at partner institutions around the world.
With its funding recently renewed for another five years, the CEMB has entered into a new phase of its mission, centered on the nascent concept of “mechanointelligence,” which is exemplified by studies like this one. While mechanobiology is the study of the physical forces that govern the behavior of cells and their communication with their neighbors, mechanointelligence adds another layer of complexity: attempting to understand the forces that allow cells to sense, remember and adapt to their environments.
Ultimately, harnessing these forces would allow researchers to help multicellular organisms — plants, animals and humans — better adapt to their environments as well.
This story originally appeared in Penn Engineering Today.
Vivek Shenoy is Eduardo D. Glandt President’s Distinguished Professor in Materials Science and Engineering, Bioengineering, and in Mechanical Engineering and Applied Mechanics.
The award from Japan’s oldest private university honors outstanding contributions to medicine and life sciences.
Richard W. Vague Professor in Immunotherapy Carl June.
Carl June,the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine in the Perelman School of Medicine and director of the Center for Cellular Immunotherapies at Penn’s Abramson Cancer Center, has been named a 2022 Keio Medical Science Prize Laureate. He is recognized for his pioneering role in the development of CAR T cell therapy for cancer, which uses modified versions of patients’ own immune cells to attack their cancer.
The Keio Medical Science Prize is an annual award endowed by Keio University, Japan’s oldest private university, which recognizes researchers who have made an outstanding contribution to the fields of medicine or the life sciences. It is the only prize of its kind awarded by a Japanese university, and eight laureates of this prize have later won the Nobel Prize. Now in its 27th year, the prize encourages the expansion of researcher networks throughout the world and contributes to the well-being of humankind.
“Dr. June exemplifies the spirit of curiosity and fortitude that make Penn home to so many ‘firsts’ in science and medicine,” said Penn President Liz Magill. “His work provides hope to cancer patients and their families across the world, and inspiration to our global community of physicians and scientists who are working to develop the next generation of treatments and cures for diseases of all kinds.”
CPE4H is one of the focal points of Penn Engineering signature initiative on Engineering Health.
The Penn Center for Precision Engineering for Health (CPE4H) was established late last year to accelerate engineering solutions to significant problems in healthcare. The center is one of the signature initiatives for Penn’s School of Engineering and Applied Science and is supported by a $100 million commitment to hire faculty and support new research on innovative approaches to those problems.
Acting on that commitment, CPE4H solicited proposals during the spring of 2022 for seed grants of $80K per year for two years for research projects that address healthcare challenges in several key areas of strategic importance to Penn: synthetic biology and tissue engineering, diagnosis and drug delivery, and the development of innovative devices. While the primary investigators (PIs) for the proposed projects were required to have a primary faculty appointment within Penn Engineering, teams involving co-PIs and collaborators from other schools were eligible for support. The seed program is expected to continue for the next four years.
“It was a delight to read so many novel and creative proposals,” says Daniel A. Hammer, Alfred G. and Meta A. Ennis Professor in Bioengineering and the Inaugural Director of CPE4H. “It was very hard to make the final selection from a pool of such promising projects.”
Judged on technical innovation, potential to attract future resources, and ability to address a significant medical problem, the following research projects were selected to receive funding.
Evolving and Engineering Thermal Control of Mammalian Cells
Led by Lukasz Bugaj, Assistant Professor in Bioengineering, this project will engineer molecular switches that can be toggled on and off inside mammalian cells at near-physiological temperatures. Successful development of these switches will provide new ways to communicate with cells, an advance that could be used to make safer and more effective cellular therapies. The project will use directed evolution to generate and find candidate molecular tools with the desired properties. Separately, the research will also develop new technology for manipulating cellular temperature in a rapid and programmable way. Such devices will enhance the speed and sophistication of studies of biological temperature regulation.
A Quantum Sensing Platform for Rapid and Accurate Point-of-Care Detection of Respiratory Viral Infections
Combining microfluidics and quantum photonics, PI Liang Feng, Professor in Materials Science and Engineering and Electrical and Systems Engineering, Ritesh Agarwal, Professor in Materials Science Engineering, and Shu Yang, Joseph Bordogna Professor in Materials Science and Engineering and Chemical and Biomolecular Engineering, are teaming up with Ping Wang, Professor of Pathology and Laboratory Medicine in Penn’s Perelman School of Medicine, to design, build and test an ultrasensitive point-of-care detector for respiratory pathogens. In light of the COVID-19 pandemic, a generalizable platform for rapid and accurate detection of viral pathogenesis would be extremely important and timely.
Versatile Coacervating Peptides as Carriers and Synthetic Organelles for Cell Engineering
PI Amish Patel, Associate Professor in Chemical and Biomolecular Engineering, and Matthew C. Good, Associate Professor of Cell and Developmental Biology in the Perelman School of Medicine and in Bioengineering, will design and create small proteins that self-assemble into droplet-like structures known as coacervates, which can then pass through the membranes of biological cells. Upon cellular entry, these protein coacervates can disassemble to deliver cargo that modulates cell behavior or be maintained as synthetic membraneless organelles. The team will design new chemistries that will facilitate passage across cell membranes, and molecular switches to sequester and release protein therapeutics. If successful, this approach could be used to deliver a wide range of macromolecule drugs to cells.
Towards an Artificial Muscle Replacement for Facial Reanimation
Cynthia Sung, Gabel Family Term Assistant Professor in Mechanical Engineering and Applied Mechanics and Computer Information Science, will lead a research team including Flavia Vitale, Assistant Professor of Neurology and Bioengineering, and Niv Milbar, Assistant Instructor in Surgery in the Perelman School of Medicine. The team will develop and validate an electrically driven actuator to restore basic muscle responses in patients with partial facial paralysis, which can occur after a stroke or injury. The research will combine elements of robotics and biology, and aims to produce a device that can be clinically tested.
“These novel ideas are a great way to kick off the activities of the center,” says Hammer. “We look forward to soliciting other exciting seed proposals over the next several years.”
Penn Health-Tech director Katie Reuther (center) with Glory Durham, director of operations, Penn Health-Tech (at left), and Courtney Houtsma, program manager, Penn Health-Tech (at right), at a recent symposium.
A new interview in Penn Medicine News examines Penn Health-Tech (PHT) five years after its founding. PHT began as an experimental collaborative effort between the Perelman School of Medicine, the School of Engineering and Applied Science, and the Office of the Vice Provost for Research to provide funding, advising, and resources to empower innovators to develop transformative devices and technologies in the Penn community. Specifically, PHT specializes in connecting innovators from across Penn’s campus and schools to connect and to develop technology and medical devices to answer some of the most pressing needs in healthcare. Katherine (Katie) Reuther, Practice Associate Professor in Bioengineering, was appointed Executive Director of PHT in 2021 and is leading this venture into the next phase of its growth. Reuther, an alumna of Penn Bioengineering, followed up her doctoral studies with a M.B.A. from Columbia University and subsequently stayed at Columbia as Senior Lecturer in Design, Innovation, and Entrepreneurship in the Department of Biomedical Engineering. As such, her experience and expertise in the fields of both biomedical engineering and entrepreneurship position her well to shepherd PHT into its fullest potential:
“What appealed to me most about the position was a strong foundation, deep resources, and the potential and room to do more, including the opportunity to elevate Penn and Philadelphia as a national hub for health-technology innovation.”
Combining optical measurements with ultrasound, an interdisciplinary team from the School of Arts & Sciences, Perelman School of Medicine, and CHOP developed a device to better measure blood flow and oxygenation in the placenta. (Image: Lin Wang)
A study published in Nature Biomedical Engineering details a novel method for imaging the placenta in pregnant patients as well as the results of a pilot clinical study. By combining optical measurements with ultrasound, the findings show how oxygen levels can be monitored noninvasively and provides a new way to generate a better understanding of this complex, crucial organ. This research was the result of a collaboration of the groups of the University of Pennsylvania’s Arjun Yodh and Nadav Schwartz with colleagues from the Children’s Hospital of Philadelphia (CHOP) and was led by postdoc Lin Wang.
Schwartz describes the placenta as the “engine” of pregnancy, an organ that plays a crucial role in delivering nutrients and oxygen to the fetus. Placental dysfunction can lead to complications such as fetal growth restriction, preeclampsia, and stillbirth. To increase knowledge about this crucial organ, the National Institute of Child Health and Human Development launched the Human Placenta Project in 2014. One focus of the program is to develop tools to assess human placental structure and function in real time, including optical devices.
For three years, the researchers optimized the design of their instrument and tested it in preclinical settings. The process involved integrating optical fibers with ultrasound probes, exploring various ultrasound transducers, and improving the multimodal technology so that measurements were stable, accurate, and reproducible while collecting data at the bedside. The resulting instrumentation now enables researchers to study the anatomy of the placenta while also collecting detailed functional information about placenta blood flow and oxygenation, capabilities that existing commercially devices do not have, the researchers say.
Because the placenta is located far below the body’s surface, one of the key technical challenges addressed by Wang, a postdoc in Yodh’s lab, was reducing background noise in the opto-electronic system. Light is scattered and absorbed when it travels through thick tissues, Yodh says, and the key for success was to reduce background interference so that the small amount of light that penetrates deep into the placenta and then returns is still large enough for a high-quality measurement.
“We’re sending a light signal that goes through the same deep tissues as the ultrasound. The extremely small amount of light that returns to the surface probe is then used to accurately assess tissue properties, which is only possible with very stable lasers, optics, and detectors,” says Yodh. “Lin had to overcome many barriers to improve the signal-to-noise ratio to the point where we trusted our data.”
The authors are Lin Wang, Jeffrey M. Cochran, Kenneth Abramson, Lian He, Venki Kavuri, Samuel Parry, Arjun G. Yodh, and Nadav Schwartz from Penn; Tiffany Ko, Wesley B. Baker, and Rebecca L. Linn from the Children’s Hospital of Philadelphia, and David R. Busch, previously a research associate at Penn and now at the University of Texas Southwestern Medical School.
This research was supported by National Institutes of Health grants F31HD085731, R01NS113945, R01NS060653, P41EB015893, P41EB015893, T32HL007915, and U01HD087180.
Congratulations to Kevin B. Johnson, David L. Cohen University Professor, on his recent appointed as a Senior Fellow in the Leonard Davis Institute of Health Economics at the University of Pennsylvania (Penn LDI). Johnson, an expert in health care innovation and health information technology, holds appointments in Biostatistics, Epidemiology and Informatics in the Perelman School of Medicine and Computer and Information Science in the School of Engineering and Applied Science. He also holds secondary appointments in Bioengineering, Pediatrics, and in the Annenberg School of Communication and is Vice President for Applied Informatics in the University of Pennsylvania Health System.
Penn LDI is Penn’s hub for health care delivery, health policy, and population health, we connect and amplify experts and thought-leaders and train the next generation of researchers. Johnson joins over 500 Fellows from across all of Penn’s schools, the University of Pennsylvania Health System, and the Children’s Hospital of Philadelphia. Johnson brings expertise in Health Care Innovation, Health Information Technology, Medication Adherence, and Social Media to his new fellowship and has extensively studied healthcare informatics with the goal of improving patient care.
Brian Litt, MD, Professor in Neurology, Neurosurgery and Bioengineering and Director of the Penn Epilepsy Center, has received a 2022 Landis Award for Outstanding Mentorship from the National Institute of Neurological Disorders and Stroke (NINDS). This award honors Litt’s dedication to superior mentorship and training in neuroscience research. The award includes $100,000 in the form of a supplement to an existing NINDS grant to support his efforts to foster the career advancement of additional trainees.
The inaugural class of the CiPD NIDCR T90/R90 Postdoctoral Training Program Fellows with Dean Mark Wolff (center); Dr. Michel Koo, Founding Director of CiPD (far right); and CiPD Co-Director Dr. Kathleen Stebe of Penn’s School of Engineering and Applied Science (far left).
With one of its key missions to develop a new generation of scientists at the interface of dental medicine and engineering, the Center for Innovation & Precision Dentistry (CiPD) has selected its inaugural class of fellows for its new postdoctoral training program.
The CiPD was awarded a $2.5 million T90/R90 grant from the National Institute of Dental and Craniofacial Research (NIDCR) last summer to establish the program, recently naming this first cohort of fellows that includes Justin Burrell, Marshall Padilla, Zhi Ren, and Dennis Sourvanos.
“We’re hoping this program will promote cross-pollination and create a culture between these two fields to help dentists develop innovative strategies with engineers,” says Penn Dental Medicine’s Michel Koo, Co-Director of CiPD, who launched the Center in 2021 with Co-Director Kathleen Stebe, Richer & Elizabeth Goodwin Professor in Penn Engineering’s Department of Chemical and Biomolecular Engineering. “Dentists can learn from engineering principles and tools, and engineers can understand more about the needs of the dental and craniofacial fields. We’re providing a platform for them to work together to address unmet clinical needs and develop careers in that interface.”
The NIDCR T90/R90 Postdoctoral Training Program aims to specifically focus on the oral microbiome, host immunity, and tissue regeneration, each of which ties into different aspects of oral health, from tooth decay and periodontal disease to the needs of head and neck cancer patients. To advance these areas, emerging approaches, from advanced materials, robotics, and artificial intelligence to tissue engineering, chloroplast- and nanoparticle-based technologies, will be leveraged.
As part of the two-year training, each postdoc will receive co-mentorship from faculty from each school in conjunction with a career development committee of clinicians, basic scientists, as well as engineers. These mentorships will be focused on research outcomes and readying participants to submit grants and compete for positions in academia or industry.
The inaugural class of fellows includes Justin Burrell, a postdoctoral student in the lab of D. Kacy Cullen, Associate Professor of Neurosurgery; Marshall Padilla, a postdoc in the lab of Michael J. Mitchell, Skirkanich Assistant Professor of Innovation in Bioengineering; and Zhi Ren, a postdoc in the lab of Michael Koo; and Dennis Sourvanos, an Advanced Graduate Dental Education resident at Penn Dental Medicine whose research has been co-directed by Timothy C. Zhu, Professor of Radiation Oncology in the Perelman School of Medicine. Cullen, Mitchell, Koo and Zhu are all members of the Penn Bioengineering Graduate Group.
Penelope earned her Ph.D. in Bioengineering in 2006. She is now Associate Director of STEM Initiatives at Princeton University.
Penelope Georges, Ph.D.
“My time at Penn spoiled me for many job experiences that followed. The Institute for Medicine and Engineering (IME) was collaborative, familial, and stimulating. During my Ph.D. work, I felt simultaneously nurtured and challenged. Most credit for this prolific phase of my career is due to the members of Dr. Paul Janmey’s laboratory during my tenure at Penn – starting with the big man himself. My research mentor promoted a research experience that centered on respect for others, not only within our field of study but also outside the academy. Respect meant the expectation of forming strong relationships and collaborations and having reverence for scientific experts and practitioners alike. The foundation of the lab’s ethos was collaboration for the greater good.
Dr. Janmey set the tone for lab members to hold each other in high regard and to be team players. I would not have been as successful without this support. Beyond the lab, the IME at the time had a remarkable staff assistant in Marvin Jackson who was central to promoting camaraderie across the Institute. Marvin was a critical presence in the IME and I believe that many scientific collaborations were made possible due to the environment he cajoled.
Outside the IME, some the most meaningful moments of my Ph.D. studies came from traveling outside the U.S. to collaborate internationally. I was fortunate to travel as close as Mechanicsville, PA and as far as the Czech Republic to attend meetings, perform experiments, and make connections with colleagues. Through travel and meeting many different types of people, I learned the culture of being in academia and developed a broader view of scientific research.
As of recently, my career has focused on pedagogy in higher education. At Princeton, I serve within an entity that has a central mission of improving science and engineering literacy for all its constituents: the Council on Science and Technology. I develop new science and engineering courses and introduce interactive research-based teaching methods into these courses. I am involved in policy issues on STEM education at Princeton and beyond. The skills I learned at Penn that are critical to my current position are to recognize problems and design innovative solutions and the ability to communicate and collaborate with researchers across many disciplines. I am very grateful to be an alumna of a remarkable program.”
