A Protein Controlled by both Light and Temperature May Open Doors to Understanding Disease-related Cell Signal Pathways

by Melissa Pappas

The brighter edges of the cells in the middle and upper right panels show the optogenetic proteins collecting at the membrane after light exposure. At higher temperatures, however, the proteins become rapidly inactivated and thus do not stay at the membrane, resulting in the duller edges seen in the bottom right panel.

Most organisms have proteins that react to light. Even creatures that don’t have eyes or other visual organs use these proteins to regulate many cellular processes, such as transcription, translation, cell growth and cell survival.

The field of optogenetics relies on such proteins to better understand and manipulate these processes. Using lasers and genetically engineered versions of these naturally occurring proteins, known as probes, researchers can precisely activate and deactivate a variety of cellular pathways, just like flipping a switch.

Now, Penn Engineering researchers have described a new type of optogenetic protein that can be controlled not only by light, but also by temperature, allowing for a higher degree of control in the manipulation of cellular pathways. The research will open new horizons for both basic science and translational research.

Lukasz Bugaj, Bomyi Lim, and Brian Chow

Lukasz Bugaj, Assistant Professor in Bioengineering (BE), Bomyi Lim, Assistant Professor in Chemical and Biomolecular Engineering, Brian Chow, Associate Professor in BE, and graduate students William Benman in Bugaj’s lab, Hao Deng in Lim’s lab, and Erin Berlew and Ivan Kuznetsov in Chow’s lab, published their study in Nature Chemical Biology. Arndt Siekmann, Associate Professor of Cell and Developmental Biology at the Perelman School of Medicine, and Caitlyn Parker, a research technician in his lab, also contributed to this research.

The team’s original aim was to develop a single-component probe that would be able to manipulate specific cellular pathways more efficiently. The model for their probe was a protein called BcLOV4, and through further investigation of this protein’s function, they made a fortuitous discovery: that the protein is controlled by both light and temperature.

Read more in Penn Engineering Today.

Daniel A. Hammer Named Director of Center for Precision Engineering for Health

Daniel Hammer
Daniel Hammer, Ph.D.

by Evan Lerner

Earlier this year, Penn President Amy Gutmann and Vijay Kumar, Nemirovsky Family Dean of Penn’s School of Engineering and Applied Science, announced a $100 million commitment to accelerate innovations in medical technologies. Called the Center for Precision Engineering for Health (CPE4H), the initiative aims to bring together researchers from a wide range of fields to develop customizable biomaterials and implantable devices that can be tailored for individualized diagnostics, treatments and therapies.

Now, Daniel A. Hammer, Alfred G. and Meta A. Ennis Professor in Penn Engineering’s Departments of Bioengineering and Chemical and Biomolecular Engineering, has been named CPE4H’s inaugural director.

“Penn is a unique environment where innovations in healthcare can emerge very rapidly, as we’ve seen with the development of CAR-T cancer immunotherapy, and the design and delivery of mRNA vaccines,” Hammer says. “Engineering plays a central role in making those technologies functional and maximizing their impact, and CPE4H is a golden opportunity to take these technologies to the next level in a way that actually helps people.”

Read the full story in Penn Engineering Today.

PIK Professor Kevin Johnson named University Professor

Johnson, who has appointments in the Perelman School of Medicine and the School of Engineering and Applied Science, and a secondary appointment in the Annenberg School for Communication, will become the David L. Cohen University Professor.

Penn Integrates Knowledge Professor Kevin Johnson, a pediatrician who has pioneered the use of clinical information systems and artificial intelligence to improve medical research and patient care, has received a named University professorship.

Kevin Johnson, a Penn Integrates Knowledge University Professor whose work as a physician-scientist has led to medical information technologies that improve patient safety, has been named the David L. Cohen University Professor. The announcement was made today by President Amy Gutmann.

“David Cohen’s extraordinary leadership at the University and Penn Medicine, and longtime dedication to Philadelphia, has without a doubt shaped the booming campus, health system, and city we so much enjoy today,” says Gutmann. “His dedication is mirrored by the extraordinarily influential, innovative, and committed Dr. Kevin Johnson, whose university professorship will now bear Ambassador Cohen’s name.”

Johnson joined Penn this year from the Vanderbilt University School of Medicine. A board-certified pediatrician and leading medical informaticist, he holds faculty appointments in the Department of Biostatistics, Epidemiology, and Informatics in the Perelman School of Medicine and the Department of Computer and Information Science in the School of Engineering and Applied Science. He is also vice president for applied informatics at the University of Pennsylvania Health System and has secondary faculty appointments in the Perelman School of Medicine’s Department of Pediatrics and in the Annenberg School for Communication.

Cohen has served for two decades on Penn’s Board of Trustees and recently concluded a 12-year term as chair. He was confirmed by the U.S. Senate last month as United States Ambassador to Canada, bringing to the role decades of experience as a senior executive at Comcast Corp., chair of the Ballard Spahr law firm, chief of staff to Philadelphia Mayor Ed Rendell, trustee chair at Penn, and major player in a number of other business, civic, political, and philanthropic venues.

In addition to serving as a Trustee, Cohen is a Penn alum, having graduated from what is now the University of Pennsylvania Carey School of Law in 1981. His wife and son also attended the Law School. Cohen’s leadership in the University has been credited with helping guide the growth and advancement of both the University and Health System, in close partnership with both President Gutmann and her predecessor, Judith Rodin.

“It’s an honor to hold a professorship named after Mr. Cohen,” Johnson says. “Throughout his career, he has provided inspired leadership across Penn and our city and region. He is a passionate believer in uniting the public, private, and nonprofit sectors to tackle complex challenges and strengthen communities. Those who know me know that I’ve played a similar role as a pediatrician who works with technology, and who uses digital media to communicate to lay audiences about both. His passion for this city and our University’s educational mission are inspiring.”

N.B.: Johnson also holds a secondary appointment in the Department of Bioengineering. Read his full appointment announcement here.

Single-cell Cancer Detection Project Wins 2021 NEMO Prize

This scProteome-seq array shows separated protein biomarkers (green and magenta spots) from thousands of single cells.

Penn Health-Tech’s Nemirovsky Engineering and Medicine Opportunity (NEMO) Prize awards $80,000 to support early-stage ideas joining engineering and medicine. The goal of the prize is to encourage collaboration between the University of Pennsylvania’s Perelman School of Medicine and the School of Engineering and Applied Science by supporting innovative ideas that might not receive funding from traditional sources.

This year, the NEMO Prize has been awarded to a team of researchers from Penn Engineering’s Department of Bioengineering. Their project aims to develop a technology that can detect multiple cancer biomarkers in single cells from tumor biopsy samples.

As cancer cells grow in the body, one of the characteristics that influences tumor growth and response to treatment is cancer cell state heterogeneity, or differences in cell states. Methods that rapidly catalogue cell heterogeneity may be able to detect rare cells responsible for tumor growth and drug resistance.

Single-cell transcriptomics (scRNA-seq) is the standard method for studying cell states; by amplifying and analyzing the cell’s complement of RNA sequences at a given time, researchers can get a snapshot of what proteins the cell is in the process of making. However, this method does not fully capture the function of the cell. The field of proteomics, which captures the actual protein content of cells along with post-translational modifications, provides a better picture of the cell’s function, but single-cell proteomic methods with the same sensitivity as scRNA-seq do not currently exist.

Alex Hughes, Lukasz Bugaj and Andrew Tsourkas

This collaborative project, which joins Assistant Professors Alex Hughes and Lukasz Bugaj, as well as Professor Andrew Tsourkas, aims to change that by developing multiplexed, sensitive and highly specific single-cell proteomics technologies to advance our understanding of cancer, its detection and its treatment.

This new technology, called scProteome-seq, builds from Hughes’s previous work.

“My specific expertise here is as an inventor of single-cell western blotting, which is the core technology that our team is building on,” says Hughes. “Single-cell proteomics technologies of this type have a track-record of commercial translation for applications in basic science and clinical automation, so our approach has a high potential for real-world impact.”

The current technology from Hughes’ lab separates proteins in cells by their molecular weight and “blots” them on a piece of paper. Improvements to this technology included in this project will remove the limitation of using light-emitting dyes to detect different proteins and instead use DNA barcodes to differentiate them.

Read the full story in Penn Engineering Today.

BE Seminar: “Neural Engineering and the Primate Brain: Working at the Electrical and Optical Interface” (Bijan Pesaran)

Our final Penn Bioengineering seminar of the fall semester will take place this Thursday. Keep an eye on the BE events calendar for upcoming spring seminars.

Speaker: Bijan Pesaran, Ph.D.
Professor
Neural Science
New York University

Date: Thursday, December 16, 2021
Time: 3:30-4:30 PM EST
Zoom – check email for link
Room: Moore 216

Abstract: Neural engineering is enjoying an era of transformative growth. Classical methods that dominated the neurosciences for decades are being replaced by powerful new technologies. In this talk, I will discuss how to engineer electrical and optical interfaces to the primate brain. I will first present work on electrode interfaces that stimulate and record at the surface of and within the brain. I will show how simultaneously measuring and manipulating neurons immediately beneath electrode contacts during behavior delivers ground-truth data. The results have implications for electrode interface design and new generations of implantable biomedical devices. I will then turn to optical neural interfaces. Two-photon fluorescence microscopy images the activity of neurons expressing genetically-encoded calcium indicators and is most often performed in small animal models, such as the mouse, worm and fly. I will present a cellular-resolution robotic imaging platform to investigate the non-human primate brain at scale. I will finish by discussing potential applications of this technology to a range of scientific and clinical goals.

Bijan Pesaran Bio: Bijan Pesaran is interested in understanding large-scale circuits in the primate brain and how to engineer novel brain-based therapies. Bijan completed his undergraduate degree in Physics at the University of Cambridge, UK. After a year in the Theoretical Physics department at Bell Labs Murray Hill, he went on to earn his PhD in Physics at the California Institute of Technology. He then made the switch to neuroscience as a postdoctoral fellow in Biology at Caltech. Bijan has been on the faculty at New York University since 2006. He is currently a Professor of Neural Science in the Center for Neural Science. In 2013, he was a CV Starr Visiting Scholar at the Princeton Neuroscience Institute at Princeton University. Among other honors and awards, Bijan has received a Burroughs-Wellcome Career Award in the Biomedical Sciences, a Sloan Research Fellowship, a McKnight Scholar Award, the National Science Foundation CAREER Award and is a member of the Simons Collaboration for the Global Brain.

“You get what you put in”: A First-generation Penn Bioengineering Graduate Student Discusses His Journey

Joseph Lance Casila

Joseph Lance Casila, a doctoral student and Fontaine Fellow in Bioengineering, was profiled by his alma mater, the University of Guam (UOG. Casila was the first person in his family to graduate from a U.S.-accredited university and is now studying tissue engineering and regenerative medicine in the Bioengineering and Biomaterials Laboratory of Riccardo Gottardi, Assistant Professor in Bioengineering in Penn Engineering and Pediatrics in Penn Medicine and the Children’s Hospital of Philadelphia (CHOP). His research in the Gottardi lab employs “tissue engineering and drug delivery for biomedical problems relating to knees, ears, nose, and throat but specifically to pediatric airway disorders.” The article discusses Casila’s journey from valedictorian of his high school, to a first-generation undergraduate interested bioengineering, and now a graduate student studying at Penn on a full scholarship. After completing his degree, Casila hopes to bring what he’s learned back home to advance health care in Guam.

“My mentors, and especially my friends, helped me make the most of what UOG had to offer, and it paid off rewardingly,” he said. “You get what you put in.”

Read “A first-generation student’s path to an Ivy League Ph.D. program” in the University of Guam News & Announcements.

Yogesh Goyal Selected as 2021 STAT Wunderkind

Yogesh Goyal, Ph.D.

Yogesh Goyal, Ph.D.,  a postdoctoral researcher in Genetics and Bioengineering, has been selected as a 2021 STAT Wunderkind, which honors the “next generation of scientific superstars.” Goyal’s research is centered around developing novel mathematical and experimental frameworks to study how a rare subpopulation of cancer cells are able to survive drug therapy and develop resistance, resulting in relapse in patients. In particular, his work provides a view of different paths that single cancer cells take when becoming resistant, at unprecedented resolution and scale. This research aims to help devise novel therapeutic strategies to combat the challenge of drug resistance in cancer.

Goyal is a Jane Coffin Childs Postdoctoral Fellow in the systems biology lab of Arjun Raj, Professor in Bioengineering and Genetics at Penn. He will begin an appointment as Assistant Professor in the Department of Cell and Developmental Biology (CDB) in the Feinberg School of Medicine at Northwestern University in spring 2022.

Read the announcement in Penn Medicine News.

Penn Researchers Show ‘Encrypted’ Peptides Could be Wellspring of Natural Antibiotics

by Melissa Pappas

César de la Fuente, Ph.D.

While biologists and chemists race to develop new antibiotics to combat constantly mutating bacteria, predicted to lead to 10 million deaths by 2050, engineers are approaching the problem through a different lens: finding naturally occurring antibiotics in the human genome.

The billions of base pairs in the genome are essentially one long string of code that contains the instructions for making all of the molecules the body needs. The most basic of these molecules are amino acids, the building blocks for peptides, which in turn combine to form proteins. However, there is still much to learn about how — and where — a particular set of instructions are encoded.

Now, bringing a computer science approach to a life science problem, an interdisciplinary team of Penn researchers have used a carefully designed algorithm to discover a new suite of antimicrobial peptides, hiding deep within this code.

The study, published in Nature Biomedical Engineering, was led by César de la Fuente, Presidential Assistant Professor in Bioengineering, Microbiology, Psychiatry, and Chemical and Biomolecular Engineering, spanning both Penn Engineering and Penn Medicine, and his postdocs Marcelo Torres and Marcelo Melo. Collaborators Orlando Crescenzi and Eugenio Notomista of the University of Naples Federico II also contributed to this work.

“The human body is a treasure trove of information, a biological dataset. By using the right tools, we can mine for answers to some of the most challenging questions,” says de la Fuente. “We use the word ‘encrypted’ to describe the antimicrobial peptides we found because they are hidden within larger proteins that seem to have no connection to the immune system, the area where we expect to find this function.”

Read the full story in Penn Engineering Today.

Catherine Michelutti on “Finding New Passions” with the Orion Organisation

Catherine Michelutti (SEAS/WHARTON ’23) working on her internship in her backyard with her dog

Catherine Michelutti, a junior in Bioengineering and Wharton and fellow in the Stavros Niarchos Foundation (SNF) Paideia Program, shared her virtual internship experience with the Orion Organisation, a healthcare NGO based in South Africa that provides for “the educational, training and therapeutic needs of children, youth and adults living with physical, psychosocial challenges, intellectual and neurological disabilities”:

“My internship with the Orion Organization has prompted me to reflect on my identity in terms of where my passions and future career interests lie. My previous work experiences have all been in biomedical research fields, which is something I’m passionate about and want to continue doing throughout my career. However, working with Orion has opened my eyes to the realms of interdisciplinary work that comes with operating a healthcare NGO and the joys that come with it.”

Read the full story in the Penn Abroad blog.

BE Seminar: “Systems-level Analyses of the Human Gut Microbiome” (Ilana Lauren Brito)

Ilana Lauren Brito, Ph.D.

Speaker: Ilana Lauren Brito, Ph.D.
Assistant Professor, Mong Family Sesquicentennial Faculty Fellow in Biomedical Engineering
Meinig School of Biomedical Engineering
Cornell University

Date: Thursday, October 28, 2021
Time: 3:30-4:30 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu
Room: Moore 216

Abstract: A major question regarding the human gut microbiota is: by what mechanisms do our most intimately associated organisms affect human health? In this talk, I will present several systems-level approaches that we have developed to address this fundamental question. My lab has pioneered methods that leverage protein-protein interactions to implicate bacterial proteins in human pathways linked to disease, revealing for the first time a network of interactions that affect diseases such as colorectal cancer, inflammatory bowel disease, type 2 diabetes and obesity that can be mined for novel therapeutics and therapeutic targets. I will present novel methods that that enable deeper insight into the transcriptome of organisms within our guts and their spatial localization. Finally, I will shift to the problem of the spread of antibiotic resistance, in which the gut microbiota are implicated. Pathogens become multi-drug resistance by acquiring resistance traits carried by the gut microbiota. Studying this process in microbiomes is inherently difficult using current methods. I will present several methods that enable tracking of genes within the microbiome and computational tools that predict the network of gene transfer between bacteria. Overall, these systems-level tools provide deep insight into the knobs we can turn to engineer outcomes within the microbiome that can improve human health.

Ilana Brito Bio: Ilana Brito is an Assistant Professor of Biomedical Engineering at Cornell University. Ilana received a BA from Harvard and a PhD from MIT. She started her postdoc as an Earth Institute Postdoctoral Fellow at Columbia University where she launched the Fiji Community Microbiome Project, a study aimed at tracking microbiota across people and their social networks, and continued this work at MIT and the Broad Institute working with Eric Alm. In her lab at Cornell, Ilana and her team are developing a suite of experimental systems biology tools to probe the functions of the human microbiome in a robust, high-throughput manner. Ilana has received numerous accolades for her work, including a Sloan Research Fellowship, Packard Fellowship, a Pew Biomedical Research Scholarship and an NIH New Innovator Award.