Tag: biotechnology

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BE/MEAM Seminar: “Microbes in Biomechanics” (Christopher J. Hernandez)

Speaker: Christopher J. Hernandez, Ph.D.
Professor, Sibley School of Mechanical and Aerospace Engineering, Cornell University
Adjunct Scientist, Hospital for Special Surgery

Date: Thursday, February 4, 2021
Time: 3:00-4:00 PM EST
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “Microbes in Biomechanics”

This seminar is jointly hosted by the Department of Bioengineering and the Department of Mechanical Engineering and Applied Mechanics.

Abstract:

The idea that mechanical stresses influence the growth and form of organs and organisms originated in the 1800s and is the basis for the modern study of biomechanics and mechanobiology. Biomechanics and mechanobiology are well studied in eukaryotic systems, yet eukaryotes represent only a small portion of the diversity and abundance of life on Earth. Bacteria exhibit broad influences on human health (as both pathogens and as beneficial components of the gut microbiome) and processes used in biotechnology and synthetic biology. Over the past eight years my group has explored mechanobiology within individual bacteria and the effects of changes in the composition of commensal bacterial communities on the biomechanics in the musculoskeletal system.

The ability of the bacteria to not only resist mechanical loads (biomechanics) but also to respond to changes in the mechanical environment (mechanobiology) is necessary for survival. Here I describe a novel microfluidic platform used to explore the biomechanics and mechanobiology of individual, live bacteria. I discuss work from my group demonstrating that mechanical stress within the bacterial cell envelope can influence the assembly and function of multicomponent efflux pumps used by bacteria to resist toxins and antibiotics. Additionally, I share some of our more recent work showing that mechanical stress and strain within the bacterial cell envelope can stimulate a bacterial two-component system controlling gene expression. Our findings demonstrate that bacteria, like mammalian cells, have mechanosensitive systems that are key to survival.

In musculoskeletal disease, bacteria are commonly viewed as sources of infection. However, in the past decade the studies by my group and others have suggested that commensal bacteria – the microbiome – can modulate the pathogenesis of musculoskeletal disorders. My group is among the first to study the effects of the gut microbiome on orthopaedic disorders. Here I provide an introduction to the microbiome and current concepts of how modifications to the gut microbiome could influence the musculoskeletal system. Specifically, I discuss studies from my group which are the first to demonstrate that the gut microbiome influences bone biomechanics and the development of infection of orthopaedic implants.

Bio:

Dr. Hernandez is Professor in the Sibley School of Mechanical and Aerospace Engineering at Cornell University and is an Adjunct Scientist at the Hospital for Special Surgery. Dr. Hernandez is a Fellow of the American Institute for Medical and Biological Engineering (AIMBE), the American Society of Mechanical Engineers (ASME), and the American Society for Bone and Mineral Research (ASBMR). He is the 2018 recipient of the Fuller Albright Award for Scientific Excellence from the American Society for Bone and Mineral Research. He has served on the Board of Directors of the Orthopaedic Research Society and the American Society for Bone and Mineral Research. His laboratory’s research currently focuses on the effects of the microbiome on bone and joint disorders, periprosthetic joint infection and the biomechanics and mechanobiology of bacteria.

hernandezresearch.com

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President’s Innovation Prize Winner Strella Biotechnology Raises $3.3 Million in Seed Funding

Alumni Malika Shukurova (left) and Katherine Sizov, Strella Biotechnology

Last year, Katherine Sizov (BIO ’19) and Malika Shukurova (BE ’19) earned the 2019 President’s Innovation Prize for their plan to use Internet-of-Things technology to monitor fruit ripeness and reduce waste in produce supply chains. Their company, Strella Biotechnology, received $100,000 of financial support, a $50,000 living stipend for both awardees, and a year of dedicated co-working and lab space at the Pennovation Center.

Now, it has $3.3 million on hand as it attempts to take its technology into retail stores.

As reported in Technically Philly and the Philadelphia Business Journal, the “fruit hacking” company’s seed round funding comes from several venture capital firms, including Pennovation’s Red & Blue Ventures, as well as celebrity investor Mark Cuban.

Strella’s ethylene sensors are already being used by fruit packers in order to more precisely time shipments as their produce ripens. The Penn start-up company thinks retailers could similarly benefit when it comes to deciding when to put their stock out for sale.

Read more at Technically Philly and the Philadelphia Business Journal.

Originally posted on the Penn Engineering Blog.

NB: The initial work for Strella Biotechnology was done by Sizov in Penn Bioengineering’s  George H. Stephenson Foundation Educational Laboratory and Bio-MakerSpace. Read more about how BE’s Bio-MakerSpace has become a hub for start-ups here.

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The Optimal Immune Repertoire for Bacteria

by Erica K. Brockmeier

Transmission electron micrograph of multiple bacteriophages, viruses that infect bacteria, attached to a cell wall. New research describes how bacteria can optimize their “memory” of past viral infections in order to launch an effective immune response against a new invader. (Image: Graham Beards)

Before CRISPR became a household name as a tool for gene editing, researchers had been studying this unique family of DNA sequences and its role in the bacterial immune response to viruses. The region of the bacterial genome known as the CRISPR cassette contains pieces of viral genomes, a genomic “memory” of previous infections. But what was surprising to researchers is that rather than storing remnants of every single virus encountered, bacteria only keep a small portion of what they could hold within their relatively large genomes.

Work published in the Proceedings of the National Academy of Sciences provides a new physical model that explains this phenomenon as a tradeoff between how much memory bacteria can keep versus how efficiently they can respond to new viral infections. Conducted by researchers at the American Physical Society, Max Planck Institute, University of Pennsylvania, and University of Toronto, the model found an optimal size for a bacteria’s immune repertoire and provides fundamental theoretical insights into how CRISPR works.

In recent years, CRISPR has become the go-to biotechnology platform, with the potential to transform medicine and bioengineering. In bacteria, CRISPR is a heritable and adaptive immune system that allows cells to fight viral infections: As bacteria come into contact with viruses, they acquire chunks of viral DNA called spacers that are incorporated into the bacteria’s genome. When the bacteria are attacked by a new virus, spacers are copied from the genome and linked onto molecular machines known as Cas proteins. If the attached sequence matches that of the viral invader, the Cas proteins will destroy the virus.

Bacteria have a different type of immune system than vertebrates, explains senior author Vijay Balasubramanian, but studying bacteria is an opportunity for researchers to learn more about the fundamentals of adaptive immunity. “Bacteria are simpler, so if you want to understand the logic of immune systems, the way to do that would be in bacteria,” he says. “We may be able to understand the statistical principles of effective immunity within the broader question of how to organize an immune system.”

Read more on Penn Today.

Vijay Balasubramanian is the Cathy and Marc Lasry Professor in the Department of Physics and Astronomy in the School of Arts & Sciences at the University of Pennsylvania and a member of the Department of Bioengineering Graduate Group. 

This research was supported by the Simons Foundation (Grant 400425) and National Science Foundation Center for the Physics of Biological Function (Grant PHY-1734030). 

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Daniel A. Hammer and Miriam Wattenbarger to Offer Summer Course on COVID-19

Daniel A. Hammer and Miriam Wattenbarger

As researchers hunt for a solution to the coronavirus outbreak, Daniel A. Hammer, Alfred G. and Meta A. Ennis Professor in Bioengineering and in Chemical and Biomolecular Engineering (CBE), is bringing lessons from the fight for a vaccine to the classroom.

Hammer will offer a course on COVID-19 and the coronavirus pandemic during Penn’s Summer II session, which will be held online this year. The course will be co-taught with Miriam Wattenbarger, senior lecturer in CBE.

The course, “Biotechnology, Immunology, and COVID-19,” will culminate with a case study of the coronavirus pandemic including the types of drugs proposed and their mechanism of action, as well as the process of vaccine development.

“Obviously, the pandemic has been a life-altering event, causing an immense dislocation for everyone in our community, especially the students. Between me and Miriam, who has been trumpeting the importance of vaccines for some time in her graduate-level CBE courses, we have the expertise to inform students about this disease and how we might combat it,” says Hammer.

For more than ten years, Wattenbarger has run courses and labs focused on drug delivery and biotechnology, key elements of the vaccine development process.

“I invite both researchers and industry speakers to meet with my students,” Wattenbarger says, “so that they learn the crucial role engineers play in both vaccine development and manufacturing.”

Beyond studying the interactions between the immune system and viruses — including HIV, influenza, adenovirus and coronavirus — students will cover a variety of biotechnological techniques relevant to tracking and defending against them, including recombinant DNA technology, polymerase chain reaction, DNA sequencing, gene therapy, CRISPR-Cas9 editing, drug discovery, small molecule inhibitors, vaccines and the clinical trial process.

Students will also learn the mathematical principles used to quantify biomolecular interactions, as well as those found behind simple epidemiological models and methods for making and purifying drugs and vaccines.

“We all have to contribute in the ways that we can. Having taught biotechnology to freshmen for the past decade, this is something that I can do that can both inform and build community,” says Hammer. “Never has it been more important to have an informed and scientifically literate community that can fight this or any future pandemic.”

Originally posted on the Penn Engineering blog. Media contact Evan Lerner. For more on BE’s COVID-19 projects, read our recent blog post.

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Bioengineering News Round-Up (April 2020)

by Sophie Burkholder

How to Heal Chronic Wounds with “Smart” Bandages

Some medical conditions, like diabetes or limb amputation, have the potential to result in wounds that never heal, affecting patients for the rest of their lives. Though normal wound-healing processes are relatively understood by medical professionals, the complications that can lead to chronic non-healing wounds are often varied and complex, creating a gap in successful treatments. But biomedical engineering faculty from the University of Connecticut want to change that.

Ali Tamayol, Ph.D., an Associate Professor in UConn’s Biomedical Engineering Department, developed what he’s calling a “smart” bandage in collaboration with researchers from the University of Nebraska-Lincoln and Harvard Medical School. The bandage, paired with a smartphone platform, has the ability to deliver medications to the wound via wirelessly controlled mini needles. The minimally invasive device thus allows doctors to control medication dosages for wounds without the patient even having to come in for an appointment. Early tests of the device on mice showed success in wound-healing processes, and Tamayol hopes that soon, the technology will be able to do the same for humans.

A New Patch Could Fix Broken Hearts

Heart disease is by far one of the most common medical conditions in the world, and has a high risk of morbidity. While some efforts in tissue engineering have sought to resolve cardiac tissue damage, they often require the use of existing heart cells, which can introduce a variety of complications to its integration into the human body. So, a group of bioengineers at Trinity College in Dublin sought to eliminate the need for cells by creating a patch that mimics both the mechanical and electrical properties of cardiac tissue.

Using thermoelastic polymers, the engineers, led by Ussher Assistant Professor in Biomedical Engineering Michael Monaghan, Ph.D., created a patch that could withstand multiple rounds of stretching and exhibited elasticity: two of the biggest challenges in designing synthetic cardiac tissues. With the desired mechanical properties working, the team then coated the patches with an electroconductive polymer that would allow for the necessary electrical signaling of cardiac tissue without decreasing cell compatibility in the patch. So far, the patch has demonstrated success in both mechanical and electrical behaviors in ex vivo models, suggesting promise that it might be able to work in the human body, too.

3-D Printing a New Tissue Engineering Scaffold

While successful tissue engineering innovations often hold tremendous promise for advances in personalized medicine and regeneration, creating the right scaffold for cells to grow on either before or after implantation into the body can be tricky. One common approach is to use 3-D printers to extrude scaffolds into customizable shapes. But the problem is that not all scaffold materials that are best for the body will hold up their structure in the 3-D printing process.

A team of biomedical engineers at Rutgers University led by Chair of Biomedical Engineering David I. Schreiber, Ph.D., hopes to apply the use of hyaluronic acid — a common natural molecule throughout the human body — in conjunction with polyethylene glycol to create a gel-like scaffold. The hope is that the polyethylene glycol will improve the scaffold’s durability, as using hyaluronic acid alone creates a substance that is often too weak for tissue engineering use. Envisioning this gel-like scaffold as a sort of ink cartridge, the engineers hope that they can create a platform that’s customizable for a variety of different cells that require different mechanical properties to survive. Notably, this new approach can specifically control both the stiffness and the ligands of the scaffold, tailoring it to a number of tissue engineering applications.

A New Portable Chip Can Track Wide Ranges of Brain Activity

Understanding the workings of the human brain is no small feat, and neuroscience still has a long way to go. While recent technology in brain probes and imaging allows for better understanding of the organ than ever before, that technology often requires immense amounts of wires and stationary attachments, limiting the scope of brain activity that can be studied. The answer to this problem? Figure out a way to implant a portable probe into the brain to monitor its everyday signaling pathways.

That’s exactly what researchers from the University of Arizona, George Washington University, and Northwestern University set out to do. Together, they created a small, wireless, and battery-free device that can monitor brain activity by using light. The light-sensing works by first tinting some neurons with a dye that can change its brightness according to neuronal activity levels. Instead of using a battery, the device relies on energy from oscillating magnetic fields that it can pick up with a miniature antenna. Led in part by the University of Arizona’s Gutruf Lab, the new device holds promise for better understanding how complex brain conditions like Alzheimer’s and Parkinson’s might work, as well as what the mechanisms of some mental health conditions look like, too.

People & Places

Each year, the National Academy of Engineering (NAE) elects new members in what is considered one of the highest professional honors in engineering. This year, NAE elected 87 new members and 18 international members, including a former Penn faculty member and alumna Susan S. Margulies, Ph.D. Now a professor of Biomedical Engineering at Georgia Tech and Emory University, Margulies was recognized by the NAE for her contributions to “elaborating the traumatic injury thresholds of brain and lung in terms of structure-function mechanisms.” Congratulations, Dr. Margulies!

Nimmi Ramanujam, Ph.D., a Distinguished Professor of Bioengineering at Duke University, was recently announced as having one of the highest-scoring proposals for the MacArthur Foundation’s 100&Change competition for her proposal “Women-Inspired Strategies for Health (WISH): A Revolution Against Cervical Cancer.” Dr. Ramanujam’s proposal, which will enter the next round of competition for the grant, focuses on closing the cervical cancer inequity gap by creating a new model of women-centered healthcare.

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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 .

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Strella Biotechnology’s Biosensors Minimize Food Waste, One Apple at a Time

By Erica K. Brockmeier

BE Senior Malika Shukurova (left) with her partner Katherine Sizov, Strella Biotechnology

Bringing home a bad apple or two from the grocery store might not seem like a huge deal to the average consumer. But for producers and sellers of fresh fruits and vegetables, the staggering 40% of food that goes bad before it even reaches a store means mounds of wasted food and nearly $1 trillion in lost profits.

Now, thanks to a 2019 President’s Innovation Prize (PIP) award, seniors Katherine Sizov of Alexandria, Virginia, and Malika Shukurova of Samarkand, Uzbekistan, plan to address the issue and optimize the produce supply chain. The prize will help them grow their novel biosensing technology startup company Strella Biotechnology.

Sizov, who is majoring in molecular biology, likes to ask everyone the same question when talking about Strella: “How old do you think an apple in a grocery store is?” As it turns out, an apple from a store may have been in storage anywhere from a couple months to up to more than a year. “That’s one fact that you don’t really consider when you go into a store because you’re so used to seeing fresh fruit,” she says.

The idea for Strella came to life when Sizov, who was previously doing undergraduate research on neurodegenerative disorders, found herself reading papers outside of her main area of study and chatting with Shukurova about what she learned about food waste. The two friends had met during freshmen year through the Penn Russian Club.

That 40% of all fresh produce going to waste is what motivated Sizov. “I thought it was the most ridiculous number in the world,” she says. “This clearly is a problem that could be solved, and, since ag is a bio space, I thought we could use the technical knowledge that we have to solve the problem.”

Shukurova, a bioengineering major, quickly became interested in seeking a solution with Sizov. “At that time I was becoming increasingly interested in the technical aspects [of the problem], and more focused towards building a solution by sensing,” she says. Their complementary areas of technical expertise, and two years of friendship, led to a collaboration.

They soon found a potential approach: Ripening fruits release ethylene gas, and the amount of the gas correlates with a fruit’s ripeness. The challenge, however, is that man-made compounds do not bind ethylene with much specificity, so it’s a difficult gas to measure.

Strella’s solution? “Hack the fruit,” says Sizov, explaining that fruits can already measure ethylene themselves. Placing a ripe banana next to an unripe banana, for example, causes the unripe fruit to ripen more quickly. “Why reinvent the wheel? Let’s use what a fruit uses to sense ethylene,” she says.

After Sizov “hacked” the fruit and had a potential biosensor in hand, Shukurova’s experience and technical knowledge in bioengineering gave her knowledge on both the electronic and biological aspects of the problem. Their patent-pending sensor is now a “leading ripeness indicator” that Strella can monitor on a constant basis.

But bringing their biosensor to market means overcoming technical and biological challenges, including biosensor stability and powering the electrical components that collect data. Sizov and Shukurova put together a team of people with complementary knowledge, including Zuyang Liu, an electrical engineering master’s student; Reggie Lamaute, an undergraduate studying chemistry and nanotechnology; and Jay Jordan, who has previous experience in sales and market development in agriculture.

Strella biotechnology came together thanks to a number of programs and resources at Penn, including the Wharton VIP-Xcelerate, the Wharton VIP Fellows program, Weiss Tech House, the Wharton Undergraduate Entrepreneurship Club, the Penn Engineering Miller Innovation Fellowship, and courses offered as part of the Engineering and Entrepreneurship Program. Sizov and Shukurova also say that Penn’s openness to innovation and the numerous resources for would-be entrepreneurs has expedited their success.

Mentorship was also crucial for the success of their startup, with both naming Sevile Mannickarottu and their PIP mentor, Jeffrey Babin, as instrumental resources. Babin, who first met Sizov when she took his engineering entrepreneurship lab and who later served as her Wharton accelerator program advisor, says that Sizov was able to take skills she gained in the classroom and directly apply them in business scenarios. “She’s fearless in terms of picking up the phone and talking to strangers, gauging the market place, and taking on the tough issues in starting a company,” he says.

Continue reading at Penn Today.