Week in BioE (July 12, 2019)

by Sophie Burkholder

DNA Microscopy Gives a Better Look at Cell and Tissue Organization

A new technique that researchers from the Broad Institute of MIT and Harvard University are calling DNA microscopy could help map cells for better understanding of genetic and molecular complexities. Joshua Weinstein, Ph.D., a postdoctoral associate at the Broad Institute, who is also an alumnus of Penn’s Physics and Biophysics department and former student in Penn Bioengineering Professor Ravi Radhakrishnan’s lab, is the first author of this paper on optics-free imaging published in Cell.

The primary goal of the study was to find a way of improving analysis of the spatial organization of cells and tissues in terms of their molecules like DNA and RNA. The DNA microscopy method that Weinstein and his team designed involves first tagging DNA, and allowing the DNA to replicate with those tags, which eventually creates a cloud of sorts that diffuses throughout the cell. The DNA tags subsequent interactions with molecules throughout the cell allowed Weinstein and his team to calculate the locations of those molecules within the cell using basic lab equipment. While the researchers on this project focused their application of DNA microscopy on tracking human cancer cells through RNA tags, this new method opens the door to future study of any condition in which the organization of cells is important.

Read more on Weinstein’s research in a recent New York Times profile piece.

Penn Engineers Demonstrate Superstrong, Reversible Adhesive that Works like Snail Slime

A snail’s epiphragm. (Photo: Beocheck)

If you’ve ever pressed a picture-hanging strip onto the wall only to realize it’s slightly off-center, you know the disappointment behind adhesion as we typically experience it: it may be strong, but it’s mostly irreversible. While you can un-stick the used strip from the wall, you can’t turn its stickiness back on to adjust its placement; you have to start over with a new strip or tolerate your mistake. Beyond its relevance to interior decorating, durable, reversible adhesion could allow for reusable envelopes, gravity-defying boots, and more heavy-duty industrial applications like car assembly.

Such adhesion has eluded scientists for years but is naturally found in snail slime. A snail’s epiphragm — a slimy layer of moisture that can harden to protect its body from dryness — allows the snail to cement itself in place for long periods of time, making it the ultimate model in adhesion that can be switched on and off as needed. In a new study, Penn Engineers demonstrate a strong, reversible adhesive that uses the same mechanisms that snails do.

This study is a collaboration between Penn Engineering, Lehigh University’s Department of Bioengineering, and the Korea Institute of Science and Technology.

Read the full story on Penn Engineering’s Medium blog. 

Low-Dose Radiation CT Scans Could Be Improved by Machine Learning

Machine learning is a type of artificial intelligence growing more and more popular for applications in bioengineering and therapeutics. Based on learning from patterns in a way similar to the way we do as humans, machine learning is the study of statistical models that can perform specific tasks without explicit instructions. Now, researchers at Rensselaer Polytechnic Institute (RPI) want to use these kinds of models in computerized tomography (CT) scanning by lowering radiation dosage and improving imaging techniques.

A recent paper published in Nature Machine Intelligence details the use of modularized neural networks in low-dose CT scans by RPI bioengineering faculty member Ge Wang, Ph.D., and his lab. Since decreasing the amount of radiation used in a scan will also decrease the quality of the final image, Wang and his team focused on a more optimized approach of image reconstruction with machine learning, so that as little data as possible would be altered or lost in the reconstruction. When tested on CT scans from Massachusetts General Hospital and compared to current image reconstruction methods for the scans, Wang and his team’s method performed just as well if not better than scans performed without the use of machine learning, giving promise to future improvements in low-dose CT scans.

A Mind-Controlled Robotic Arm That Requires No Implants

A new mind-controlled robotic arm designed by researchers at Carnegie Mellon University is the first successful noninvasive brain-computer interface (BCI) of its kind. While BCIs have been around for a while now, this new design from the lab of Bin He, Ph.D.,  a Trustee Professor and the Department Head of Biomedical Engineering at CMU, hopes to eliminate the brain implant that most interfaces currently use. The key to doing this isn’t in trying to replace the implants with noninvasive sensors, but in improving noisy EEG signals through machine learning, neural decoding, and neural imaging. Paired with increased user engagement and training for the new device, He and his team demonstrated that their design enhanced continuous tracking of a target on a computer screen by 500% when compared to typical noninvasive BCIs. He and his team hope that their innovation will help make BCIs more accessible to the patients that need them by reducing the cost and risk of a surgical implant while also improving interface performance.

People and Places

Daeyeon Lee, professor in the Department of Chemical and Biomolecular Engineering and member of the Bioengineering Graduate Group Faculty here at Penn, has been selected by the U.S. Chapter of the Korean Institute of Chemical Engineers (KIChE) as the recipient of the 2019 James M. Lee Memorial Award.

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 U.S. and Korea.”

Read the full story on Penn Engineering’s Medium blog.

We would also like to congratulate Natalia Trayanova, Ph.D., of the Department of Biomedical Engineering at Johns Hopkins University on being inducted into the Women in Tech International (WITI) Hall of Fame. Beginning in 1996, the Hall of Fame recognizes significant contributions to science and technology from women. Trayanova’s research specializes in computational cardiology with a focus on virtual heart models for the study of individualized heart irregularities in patients. Her research helps to improve treatment plans for patients with cardiac problems by creating virtual simulations that help reduce uncertainty in either diagnosis or courses of therapy.

Finally, we would like to congratulate Andre Churchwell, M.D., on being named Vanderbilt University’s Chief Diversity Officer and Interim Vice Chancellor for Equity, Diversity, and Inclusion. Churchwell is also a professor of medicine, biomedical engineering, and radiology and radiological sciences at Vanderbilt, with a long career focused in cardiology.

Bioengineering Welcomes New Faculty Member Sydney Shaffer

Sydney Shaffer, MD, PhD

The Department of Bioengineering at the University of Pennsylvania is proud to announce the appointment of Sydney Shaffer, Ph.D., as an Assistant Professor of Bioengineering. She shares a joint appointment with Pathology and Laboratory Medicine. Originally from Atlanta, GA, Dr. Shaffer received her B.S. in Chemical Engineering from Georgia Institute of Technology, coming to Penn to complete her M.D./Ph.D. work in Bioengineering and the Perelman School of Medicine. After graduating in 2018, she conducted her postdoctoral work at Penn in Cancer Biology with Dr. Junwei Shi.

Dr. Shaffer’s research is is focused on understanding how differences present in single-cells can generate phenotypes such as drug resistance in cancer, oncogenesis, differentiation, and invasion. Our approach leverages cutting-edge technologies including high-throughput imaging, single-molecule RNA FISH, fluorescent protein tagging, CRISPR/Cas9 screening, and flow cytometry to investigate rare single-cell phenomena. Further information can be found at www.sydshafferlab.com.

In addition to her exciting research, Dr. Shaffer will be an enthusiastic new member of the Bioengineering Department community. In the short term, she will be taking over the popular class BE 400 (Preceptorships in Bioengineering) which gives undergraduates the rare chance to shadow renowned physicians over a period of ten weeks. She will also serve as a faculty advisor as well as a mentor to the lucky students in her classes and lab.

Dr. Shaffer says that, “With my research interests and training at the interface of engineering and medicine, I am thrilled to be part of the highly interdisciplinary community of Penn Bioengineering.”

“Sydney has a unique combination of creativity and impact in her work,” says Solomon R. Pollack Professor and Chair Dr. David Meaney. “Her work to untangle the secrets of how single cancer cells can develop resistance to a cancer drug  therefore leading to a return of the cancer  is nothing short of stunning. We are incredibly fortunate to have her on our faculty. ”

Week in BioE (July 31, 2018)

New Data Analysis Methods

Like many other fields, biomedical research is experiencing a data explosion. Some estimates suggest that the amount of data generated from the health sciences is now doubling every eighteen months, and experts expect it to double every seventy-three days by 2020.  One challenge that researchers face is how to meaningfully analyze this data tsunami.

The challenge of interpreting data occurs at all scales, and a recent collaboration shows how new approaches can allow us to handle the volumes of data emerging at the level of individual cells to infer more about how biology “works” at this level.  Wharton Statistics Department researchers Mo Huang and Jingshu Wang (PhD Student and Postdoctoral Researcher, respectively) collaborated with Arjun Raj’s lab in Bioengineering and published their findings in recent issues of Nature Methods and Proceedings of the National Academy of Sciences.  One study focused on a de-noising technique called SAVER to provide more precise data from single cell experiments and significantly improves the ability to detect trends in a dataset, similar to how increasing sample size helps improve the ability to determine differences between experimental groups.  The second method, termed DESCEND, creates more accurate characterization of gene expression that occur in individual cells. Together these two methods will improve data collection for biologists and medical professionals working  to diagnose, monitor, and treat diseased cells.

Dr. Raj’s team contributed data to the cause and acted as consultants on the biological aspects of this research. Further collaboration involved Mingyao Li, PhD, Professor of Biostatistics at the Perelman School of Medicine, and Nancy Zhang, PD, Professor Statistics at the Wharton School. “We are so happy to have had the chance to work with Nancy and Mingyao on analyzing single cell data,” said Dr. Raj. “The things they were able to do with our data are pretty amazing and important for the field.”

Advancements in Biomaterials

This blog features many new biomaterials techniques and substances, and there are several exciting new developments to report this week. First, the journal of Nature Biomedical Engineering published a study announcing a new therapy to treat or even eliminate lung infections, such as those acquired while in hospital or as the result of cystic fibrosis, which are highly common and dangerous. Researchers identified and designed viruses to target and kill the bacteria which causes these infections, but the difficulty of administering them to patients has proven prohibitive. This new therapy, developed by researchers at the Georgia Institute of Technology, is administered as a dry powder directly to the lungs and bypasses many of the delivery problems appearing in past treatments. Further research on the safety of this method is required before clinical trials can begin.

A team at Harvard University published another recent study in Nature Biomedical Engineering announcing their creation of a tissue-engineered scale model of the left human heart ventricle. This model is made from degradable fibers that simulate the natural fibers of heart tissue. Lead investigator Professor Kevin Kit Parker, PhD, and his team eventually hope to build specific models culled from patient stem cells to replicate the features of that patient’s heart, complete with the patient’s unique DNA and any heart defects or diseases. This replica would allow researchers and clinicians to study and test various treatments before applying them to a specific patient.

Lastly, researchers at the Tufts University School of Engineering published in the Proceedings of the National Academy of Sciences on their creation of flexible magnetic composites that respond to light. This material is capable of macroscale motion and is extremely flexible, allowing its adaptation into a variety of substances such as sponges, film, and hydrogels. Author and graduate student Meg Li explained that this material differs from similar substances in its complexity; for example, in the ability for engineers to dictate specific movements, such as toward or away from the light source. Co-author Fiorenzo Omenetto, PhD, suggests that with further research, these movements could be controlled at even more specific and detailed levels.

CFPS: Getting Closer to “On Demand” Medicine

A recent and growing trend in medicine is the move towards personalized or “on demand” medicine, allowing for treatment customized to specific patients’ needs and situations. One leading method is Cell-Free Protein Synthesis (CFPS), a way of engineering cellular biology without using actual cells. CFPS is used to make substances such as medicine, vaccines, and chemicals in a sustainable and portable way. One instance if the rapid manufacture of insulin to treat diabetic patients. Given that many clinics most in need of such substances are found in remote and under-served locations far away from well-equipped hospitals and urban infrastructure, the ability to safely and quickly create and transport these vital substances to patients is vitally important.

The biggest limiting factor to CFPS is difficulty of replicating Glycosylation, a complex modification that most proteins undergo. Glycosylation is important for proteins to exert their biological function, and is very difficult to synthetically duplicate. Previously, achieving successful Glycosylation was a key barrier in CFPS. Fortunately, Matthew DeLisa, PhD, the Williams L. Lewis Professor of Engineering at Cornell University and Michael Jewett, PD, Associate Professor of Chemical and Biological Engineering at Northwestern University, have created a “single-pot” glycoprotein biosynthesis that allows them to make these critical molecules very quickly. The full study was recently published in Nature Communications. With this new method, medicine is one step closer to being fully “on demand.”

People and Places

The Institute of Electrical and Electronics Engineers (IEEE) interviewed our own Penn faculty member Danielle Bassett, PhD, the Edwardo D. Glandt Faculty Fellow and Associate Professor in Bioengineering, for their website. Dr. Bassett, who shares a joint appointment with Electrical Systems Engineering (ESE) at Penn, has published groundbreaking research in Network Neuroscience, Complex Systems, and more. In the video interview (below), Dr. Bassett discusses current research trends in neuroscience and their applications in medicine.

Finally, a new partnership between Case Western Reserve University and Cleveland Clinic seeks to promote education and research in biomedical engineering in the Cleveland area. Cleveland Clinic Lerner Research Institute‘s Chair of Biomedical Engineering, Geoff Vince, PhD, sees this as an opportunity to capitalize on the renown of both institutions, building on the region’s already stellar reputation in the field of BME. Dozens of researchers from both institutions will have the opportunity to collaborate in a variety of disciplines and projects. In addition to professional academics and medical doctors, the leaders of this new partnership hope to create an atmosphere that can benefit all levels of education, all the way down to high school students.

Week in BioE (July 25, 2018)

Advances in Stem Cell Research

Stem cell therapy has been used to treat a variety of conditions.

A paper published this month in Scientific Reports announced a new a strategy for the treatment of segmental bone defects. The new technique, called Segmental Additive Tissue Engineering (or SATE) comes from a team of researchers with the New York Stem Cell Foundation Research Institute (NYSCF). A press release from the NYSCF and an accompanying short video (below) describe the breakthrough technique, which will “[allow] researchers to combine segments of bone engineered from stem cells to create large scale, personalized grafts that will enhance treatment for those suffering from bone disease or injury through regenerative medicine.”

Segmental Additive Tissue Engineering from NYSCF on Vimeo.

Ralph Lauren Senior Investigator Guiseppe Maria de Peppo, PhD, and first author Martina Sladkova, PhD, express their hope that this new procedure will help address some of the limitations of bone grafts, such as immune system rejection, the need for growing bones in pediatric patients, and the difficulty of creating larger bone grafts made from patient stem cells.

Elsewhere in stem cell research, the Spanish Agency for Medicines and Medical Devices has given the company Viscofan BioEngineering approval to start clinical trials for stem cell therapy to treat heart failure. Already a world leader in the market for medical collagen, Viscofan is now turning its research toward using collagen (a protein found in the connective tissue of mammals) to strengthen the weakened heart muscle of those with ischemic cardiomyopathy, a type of heart failure and the leading cause of death in the world. This new “Cardiomesh” project includes collaborators from industry, academia, and hospitals to create this elastic and biodegradable product. Viscofan expects to start clinical trials after the summer of this year, and the full details can be found in Viscofan’s press release.

Federal Grant Supports International Bioengineering Research

The Canadian government awarded a $1.65 million federal grant to two top Canadian universities to develop a center based on engineering RNA. The University of Lethbridge and the Université de Sherbrooke will team up with international collaborators from the United States, Germany, France, Australia, and more and to found and develop the Ribonucleic Acid Bioengineering and Innovation Network Collaborative Research and Training Experience over the next six years. This comes as part of the Canadian government’s CREATE initiative, which awards grants to research teams across the country to support research, innovation, and jobs-creation in the sciences. These two universities are national leaders in the field of RNA research, a diverse and interdisciplinary field. This new network will focus on training of both young academics transitioning to industry and entrepreneurs looking to develop new technologies. This project is led by Hans-Joachim Wieden, PhD, Chemistry and Biochemistry faculty at the University of Lethbridge and an Alberta Innovates Strategic Chair in RNA Bioengineering.

Lehigh University Awarded Grant in Ebola Research

Close to Philadelphia in Allentown, PA, researchers at Lehigh University received a National Science Foundation (NSF) grant to support their research into one of the deadliest of modern diseases, the Ebola virus, which is highly infectious and currently without vaccine or cure. Entitled “TIM Protein-Mediated Ebola Virus-Host Cell Adhesion: Experiments and Models,” the goal of this research is to create a “predictive and quantitative model of the Ebola Virus (EBOV)-host cell interactions at the molecular through single-virus levels.” Building on past research, the investigators ultimately hope to provide the first quantitative study of this type of cell interaction. By studying how EBOV enters the body through healthy cells, the aim is to understand how it works and ultimately develop a technique to stop its entry. The lead investigator, Anand Jagota, PhD, is the current Professor and Founding Chair of Lehigh University’s Bioengineering program.

New Research in Brain Tumor Removal

The National Institute of Biomedical Imaging and Bioengineering (NIBIB) awarded a grant to Fake (Frank) Lu, PhD, Assistant Professor of Biomedical Engineering at the State University of New York (SUNY) at Binghamton in support of his research to design more accurate techniques for the removal of brain tumors. His technique, called Stimulated Raman Scattering or SRS, is a mode of identifying molecules during surgery which can be used to create a highly detailed and accurate image. Dr. Lu’s SRS techniques will improve both the speed of the surgery and the accuracy of the tissue removal. With this grant support, Dr. Lu’s team will collaborate with local universities and hospitals on collecting more data as their next step before making the technology more widely available.

People and Places

Undergraduate students at our neighbor Drexel University received the Robert Noyce Scholarship, an NSF program that supports students seeking their teacher certification in science and math at the middle school level. The co-investigators and undergraduates are from a variety of disciplines and programs across the university, including co-investigator Donald L. McEachron, PhD, Teaching Professor of Biomedical Engineering, Science and Health Systems. The students’ curriculum in the DragonsTeach Middle Years program will combine rigorous preparation for teaching STEM subjects and the foundational knowledge to work with under-served schools.

Another group of students, this time from California State University, Long Beach, used their victory in the university’s annual Innovation Challenge as an opportunity to launch a startup called Artemus Labs. Their first product, “Python,” uses body heat other physical sensations to regulate a prosthetic liner, useful in making sure prosthetic limbs are comfortable for the wearer. The students explained that their idea was driven by need, as few prosthetic manufacturers prioritize such factors as temperature or sweat regulation in the creation of their products.

Finally, the University of Southern California Viterbi School of Engineering has a new Chair of Biomedical Engineering: Professor K. Kirk Shung, PhD. Dr. Shung obtained his doctorate from the University of Washington and joined USC in 2002. With a background in electrical engineering, Dr. Shung’s research focuses on high frequency ultrasonic imaging and transducer development, and has been supported by a NIH grant as well as won multiple awards from the American Institute of Ultrasound in Medicine and the Institute of Electrical and Electronics Engineers (IEEE), among others.