BE Seminar Series: March 5th with Tara L. Deans, Ph.D.

Our next Penn Bioengineering seminar will be held this Thursday. We hope to see you there!

Speaker: Tara L. Deans, Ph.D.
Assistant Professor
Biomedical Engineering
University of Utah

Date: Thursday, March 5, 2020
Time: 12:00-1:00 pm
Location: Room 337, Towne Building

Title: “Engineering Stem Cells to Create Novel Delivery Vehicles”

 

Abstract:

Synthetic biology has transformed how cells can be reprogrammed, providing a means to reliably and predictably control cell behavior with the assembly of genetic parts into more complex gene circuits. Using approaches and tools in synthetic biology, we are programming stem cells with novel genetic tools to control genes and pathways that result in changes in stem cell fate decisions, in addition to reprogramming terminally differentiated cells to function as unique therapeutic diagnostic and delivery vehicles.

Bio:

Dr. Tara Deans received her PhD from Boston University in Biomedical Engineering. Following her postdoctoral training at Johns Hopkins University, she became an Assistant Professor in Biomedical Engineering at the University of Utah. Currently, Dr. Deans runs an applied mammalian synthetic biology laboratory where her lab focuses on building novel genetic tools to study the mechanisms of stem cell differentiation for the purpose of directing cell fate decisions. Recently, Dr. Deans received four prestigious awards to support this area of research: the NSF CAREER Award, the Office of Naval Research (ONR) Young Investigator Award, the NIH Trailblazer Award and an NIH Director’s New Innovator Award. In addition to her research, Dr. Deans was recently named a STEM Ambassador in the STEM Ambassador Program (STEMAP) at the University of Utah to engage underrepresented groups in STEM fields.

BE Seminar Series: February 27th with Michael Yaszemski, M.D., Ph.D.

Our next Penn Bioengineering seminar will be held this Thursday. We hope to see you there!

Michael Yaszemski, M.D., Ph.D.

Speaker: Michael Yaszemski, M.D., Ph.D.
The Krehbiel Endowed Professor of Orthopedic Surgery and Biomedical Engineering
Mayo Clinic

Date: Thursday, February 27, 2020
Time: 12:00-1:00 pm
Location: Room 337, Towne Building

Title: “Musculoskeletal Tissue Engineering”

 

Abstract:

The field of Tissue Engineering/Regenerative Medicine is replete with advances that have been translated to human use. However, our job is not done when a treatment for a specific disease or traumatic event has been invented and translated to humans. In order to be available to the population nationwide (or globally), our novel treatment must be manufactured, transported to the user, and administered by a physician to that user. In addition, novel treatments for rare diseases may not be amenable to manufacture by a company, and perhaps would be best manufactured by an academic medical center. I will discuss these issues that occur after successful translation of a novel treatment to human use, as well as potential strategies to address them.

Bio:

Dr. Michael Yaszemski is the Krehbiel Family Endowed Professor of Orthopedic Surgery and Biomedical Engineering at Mayo Clinic and director of its Polymeric Biomaterials and Tissue Engineering Laboratory. He is a retired USAF Brigadier General. He has served as the president of the Mayo medical staff. He received both bachelor’s and master’s degrees in chemical engineering from Lehigh University in 1977 and 1978, an M.D. from Georgetown University in 1983 and a Ph.D. in chemical engineering from Massachusetts Institute of Technology in 1995.  He served as a member of the Lehigh University Board of Trustees.

How the Bioengineering Department’s Bio-MakerSpace Became a Hub for Start-Ups

by Sophie Burkholder

The George H. Stephenson Foundation Educational Laboratory and Bio-MakerSpace, more commonly known as the Bio-MakerSpace, has recently become a hub for Penn student start-ups that continue after graduation. Beyond offering a home base for projects by Bioengineering majors, the lab is also open to Penn students, regardless of major. Unlike other departmental undergraduate labs, the Bio-MakerSpace encourages interdisciplinary projects and collaborations from students across  all different majors.

Even better, the lab has a neutral policy when it comes to intellectual property (IP), meaning all IP behind student projects belongs to the students instead of the lab or the engineering school. With a wide variety of prototyping equipment, coding and software programs installed on lab computers, and an extremely helpful lab staff, the Bio-MakerSpace provides students of all academic backgrounds the resources to turn their ideas into realities or even businesses, as a recent succession of start-ups founded in the lab has shown.

One of the most successful start-ups to come out of the Bio-MakerSpace in the last few years is Group K Diagnostics, founded by 2017 Bioengineering alumna Brianna Wronko. The company focuses on the use of a point-of-care diagnostic device called KromaHealthTM. Offering a variety of different tests based on the input of a small amount of blood, serum, or urine, the device induces a color change through a series of reactions that can be detected through image processing. Developed in part from Wronko’s senior design project (hence the name “Group K”) and in part from her experience working at an HIV clinic, Group K Diagnostics looks to expand access to care for all populations.

But not all start-ups from the Bio-MakerSpace have origins in senior design projects. Three start-ups from 2019, two of which won the Penn President’s Innovation Prize, all began as independent initiatives from students. InstaHub, founded by 2019 Wharton alumnus Michael Wong with help from Bioengineering doctoral candidate Dayo Adewole, is a company that focuses on the use of snap-on automation for light energy conservation. A simple and easy-to-install device with motion and occupancy sensors, InstaHub aims to reduce energy consumption in a way that’s simpler and cheaper than rewiring projects that might otherwise be required. Here, Adewole shares the way that access to the Bio-MakerSpace provided InstaHub with a helpful platform.

The second start-up from 2019 to come out of the Bio-MakerSpace and win a President’s Innovation Prize is Strella Biotechnology, founded by recent graduate Katherine Sizov (Biology 2019). In developing sensors with the ability to detect ethylene gas emitted by rotting fruits, Strella hopes to reduce the immense amount of food waste due to produce simply going bad in storage. With a patent-pending biosensor that mimics the way ripe fruits detect ethylene emissions of nearby rotting fruits, the technology behind Strella involves both biology and aspects of engineering. In this video, Sizov herself talks about the way that the Bio-MakerSpace opened its doors to her, and allowed her work to really take off with the help of resources she wouldn’t have easily found otherwise.

Yet another start-up to use the Bio-MakerSpace as a launch pad for innovation is BioAlert Technologies, comprised of a group of Penn engineering undergraduate and graduate students, including 2019 Bioengineering alumnus Johnny Forde and current Biotechnology student Marc Rosenberg, who is the startup’s CEO and founder. BioAlert’s innovations are in what they call continuous infection monitoring (CIM) systems, designed to detect infections in patients with diabetic foot ulcers. Often, even when properly bandaged by a doctor, these ulcers run the risk of bacterial infection once a patient returns home and continues to care for the wound. BioAlert uses their platform to assess whether or not a bacterial infection might occur in a given patient’s wound, and uses an app to alert both patients and doctors of it, so that patients can receive the proper response treatment and medication as quickly as possible.

Though each of these start-ups used the resources of the Bio-MakerSpace, they are each interdisciplinary approaches to solving real-world problems today. Paired with other student resources at Penn like courses offered under an Engineering Entrepreneurship minor, knowledge from the nearby Wharton business school professors, and competitions like the Rothberg Catalyzer, the Bio-MakerSpace allows for any student to transform their idea into a reality, and potentially take it to market.

Interested in learning more? Contact the BE Labs.

Computer-generated Antibiotics, Biosensor Band-Aids, and the Quest to Beat Antibiotic Resistance

By Michele W. Berger

Imagine if a computer could learn from molecules found in nature and use an algorithm to generate new ones. Then imagine those molecules could get printed and tested in a lab against some of the nastiest, most dangerous bacteria out there — bacteria quickly becoming resistant to our current antibiotic options.

Or consider a bandage that can sense an infection with fewer than 100 bacterial cells present in an open wound. What if that bandage could then send a signal to your phone letting you know an infection had started and asking you to press a button to trigger the release of the treatment therapy it contained?

These ideas aren’t science fiction. They’re projects happening right now, in various stages, in the lab of synthetic biologist , who joined the University as a Presidential Professor in May 2019. His ultimate goal is to develop the first computer-made antibiotics. But beyond that, his lab — which includes three postdoctoral fellows, a visiting professor, and a handful of graduate students and undergrads — has many other endeavors that sit squarely at the intersection of computer science and microbiology.

Computer-generated antibiotics

Antibiotic resistance is becoming a dangerous problem, both in the United States and worldwide. According to the , each year in the U.S., at least 2.8 million people get infections that antibiotics can’t help, and more than 35,000 die from those infections. Around the world, common ailments like pneumonia and food-borne illness are getting harder to treat.

De la Fuente poses near Penn’s “Biopond”
De la Fuente earned his bachelor’s degree in biotechnology, then a doctorate in microbiology and immunology and a postdoc in synthetic biology and computational biology. Combining these fields led him to the innovative work his lab does today.

New antibiotics are needed, and according to de la Fuente, it’s time to look beyond the traditional approach.

“We’ve relied on nature as a source of antibiotics for many, many years. My whole hypothesis is that nature has perhaps run out of inspiration,” says de la Fuente, who has appointments in the and the . “We haven’t been able to discover any new scaffolds for many years. Can we digitize that information, nature’s chemistry, to be able to create and discover new molecules?”

To do that, his team turned to amino acids, the building blocks of protein molecules. The 20 that occur naturally bond in countless sequences and lengths, then fold to form different proteins. The sequencing possibilities are expansive, more than the number of stars in the universe. “We could never synthesize all of them and just see what happens,” says postdoc Marcelo Melo. “We have to combine the chemical knowledge — decades of chemistry on these tell us how they behave — with the computational side, because a computer can find patterns unlike any human could.”

Using machine learning, the researchers provide the computer with natural molecules that successfully work against bacteria. The computer learns from those examples, then generates new, artificial molecules. “We try this back and forth and hopefully we find patterns, new patterns that we can explore, instead of blindly searching,” Melo says.

The computer can then test each artificial sequence virtually, setting aside the most successful components and tossing the rest, in a form of computational natural selection. Those pieces with the highest potential get used to create new sequences, theoretically producing better and better ones each time.

De la Fuente’s team has seen some promising results already: “A lot of the molecules we’ve synthesized have worked,” he says. “The best ones worked in animal models. They were able to reduce infections in mice — which was pretty cool, given that the computer generated the whole thing.” Still, de la Fuente says the work is years away from producing anything close to a shelf-ready antibiotic.

Continue reading on .

Penn Nanoparticles are Less Toxic to T Cells Engineered for Cancer Immunotherapy

An artist’s illustration of nanoparticles transporting mRNA into a T cell (blue), allowing the latter to express surface receptors that recognize cancer cells (red). (Credit: Ryan Allen, Second Bay Studios)

New cancer immunotherapies involve extracting a patient’s T cells and genetically engineering them so they will recognize and attack tumors. This type of therapy is not without challenges, however. Engineering a patient’s T cells is laborious and expensive. And when successful, the alterations to the immune system immediately make patients very sick for a short period of time, with symptoms including fever, nausea and neurological effects.

Now, Penn researchers have demonstrated a new engineering technique that, because it is less toxic to the T cells, could enable a different mechanism for altering the way they recognize cancer, and could have fewer side effects for patients.

The technique involves ferrying messenger RNA (mRNA) across the T cell’s membrane via a lipid-based nanoparticle, rather than using a modified HIV virus to rewrite the cell’s DNA. Using the former approach would be preferable, as it only confers a temporary change to the patient’s immune system, but the current standard method for getting mRNA past the cell membrane can be too toxic to use on the limited number of T cells that can be extracted from a patient.

Michael Mitchell, Margaret Billingsley, and Carl June

The researchers demonstrated their technique in a study published in the journal Nano Letters. It was led by Michael Mitchell, Skirkanich Assistant Professor of Innovation of bioengineering in the School of Engineering and Applied Science, and Margaret Billingsley, a graduate student in his lab.

They collaborated with one of the pioneers of CAR T therapy: Carl June, the Richard W. Vague Professor in Immunotherapy and director of the Center for Cellular Immunotherapies in the Abramson Cancer Center and the director of the Parker Institute for Cancer Immunotherapy at the Perelman School of Medicine.

Read more at Penn Engineering blog.

Alex Hughes Receives the First MIRA Award of Penn SEAS

by Sophie Burkholder

Alex Hughes, Ph.D.

We would like to congratulate Assistant Professor in Bioengineering Alex Hughes, Ph.D., on receiving the Maximizing Investigators’ Research Award (MIRA) from the National Institutes of Health (NIH), which funds investigators to create flexible and forward-thinking research programs. Hughes is the first recipient of this award in Penn’s School of Engineering and Applied Science, marking a major accomplishment for him and his lab.

The award recognizes Hughes’ efforts to create new  tools used for tissue engineering, in particular by fusing concepts from developmental biology into tissue construction efforts. Hughes believes this approach will have impacts on fundamental understanding human disease, leading to new strategies to combat them. Hughes and his lab specifically focus on kidney disease. As Hughes says, “defects in the kidney and urinary tract account for up to a third of all birth defects.” Furthermore, because kidney development involves many different kinds of cell interactions, there’s a gap in understanding exactly how these defects occur.

Unlike other grants that focus on funding projects, the MIRA prioritizes the people behind the research, giving them funding as a sign of faith in the future work they’ll choose to do. “The MIRA has allowed us significant leeway to integrate several complementary approaches here,” Hughes says. Because of this flexibility, Hughes and his lab thinks it will allow them to reach for more innovative and risky approaches in their research, in the hopes that this will lead to a better understanding of kidney defects and modes of treatment for them.