This Week in BioE (July 6, 2017)

Bioengineering of Genes and DNA

Since Watson and Crick published their initial studies detailing the double helix structure of DNA in the early 1960s, what we know about genetics and the nucleic acids underlying them has grown enormously. Consequently, what bioengineering can do with DNA and genes continually expands.

One fascinating bioengineering field that emerged in the past decade was DNA origami, which uses the well-established binding across DNA elements to create three-dimensional structures out of linear DNA sequences. Recent work has utilized this feature of DNA construction to make machines, rather than just parts, out of DNA.

Yonggang Ke, Ph.D., of Georgia Tech/Emory’s Department of Biomedical Engineering, constructed machines made of DNA that consist of arrays of units that can “switch” between “settings” by changing shape. A change in shape of one unit of an array can cause the other units in the array to shift; these changes are stimulated by inserting a previously deleted strand of DNA into the array. Although it has been known for some time that DNA could be used to store and transmit information, Dr. Ke’s research team proved for the first time that these arrays could be shaped physically into machines in the shapes of rectangles and tubes.

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DNA under a microscope

While we learn more about how to make DNA-based devices, we are also creating new technologies to manipulate DNA more rapidly.  Scientists at Rutgers and Harvard developed a process whereby thousands of genes could be cloned at one time to create enormous libraries of proteins. To achieve this goal, the authors used a technology called LASSO (long-adapter single-strand oligonucleotide) probes, which they have already used to clone a library using a human microbiome sample.

Instead of the traditional process of cloning one gene at a time, the team led by Professor Biju Parekkadan, Ph.D. at Rutgers, invented a technology to clone hundred of genes simultaneously. These cloned DNA segments are much longer than the length of DNA cloned with standard techniques, allowing us to test the functional significance of these much longer DNA segments.  The technology could impact a number of scientific fields because we will finally learn how long stretches of protein function — some parts may degrade other proteins, while other parts will interact and modify other proteins (e.g., phosphorylation, a key process in epigenetics). These new discoveries can be key for discovering new ways to engineer proteins and to manufacture new drugs that mimic the function of nature’s DNA products.

Using Sweat as a Biosensor

While the field learns more about the molecular-level control of DNA, we are also taking advantage of new micro- and nanoscale manufacturing processes to capture diagnostic information from easily accessible body fluids. Many clinical diagnostics use chemical measurements from blood to diagnose a disease or to take corrective action. This is not an ideal procedure because it requires either the collection of blood at a laboratory or the repeated collection of small blood volumes through a pinprick.  Either one hurts.

Bioengineers at the University of Texas at Dallas developed a wearable diagnostic device to detect cortisol, glucose, and IL-6 in body sweat, eliminating any painful needle sticks.  Its transmissions vary, but if optimized, the device could replace the painful and inconvenient practice of sticking one’s finger to obtain a drop of blood for glucose testing, which many patients with diabetes must do several times per day. Although insulin pumps have been available for some time, these are invasive devices that must be worn at all times.

Setton Named WashU BME Chair

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Lori A. Setton, Ph.D.

Lori A. Setton, Ph.D., a major innovator in the field of tissue regeneration and repair and a member of the Penn Bioengineering Departmental Advisory Board, has been named chair of the Department of Biomedical Engineering at Washington University in St. Louis. Her appointment begins on August 1.

An alumna of Princeton (BSE) and Columbia (MS, Ph.D.) with degrees in mechanical engineering, Dr. Setton was on the faculty at Duke until 2015, when she moved to WashU. Over the last decade or so, she has coauthored nearly 150 peer-reviewed research papers in the field of biomedical engineering, establishing a sterling reputation as a scientist and researcher.

In addition to her distinguished career in research and academia, she is also the current president of BMES, where she has been a pioneer in fostering greater diversity within the field, both in instituting a partnership with the National Society for Black Engineers (NSBE) and as a mentor at Duke, where the introduction of a mentoring program to increase diversity among under-represented minorities has been particularly successful.

“We are thrilled that Lori was recognized with this significant leadership opportunity,” said David Meaney, Ph.D., chair of the Bioengineering Department at Penn. “As a key academic on our department advisory board, Lori’s incisive input on Penn Bioengineering has been invaluable as we grow and change as a department. I know she will be an outstanding leader for WashU.”

This Week in BioE (June 29, 2017)

Bioengineering Organ Systems

Two news stories this week detailed how bioengineering and biomedical engineering are transforming how human organ systems could be better manipulated for positive effects on health.

organ systemsOne of the critical organ transplant shortages  in medicine is the gap between patients needing a liver transplant (around 13,000 each year) and the those receiving a transplant (about 7,000). For many years, bioengineers tried to build liver tissue in sophisticated 2D and 3D structures. Yet we never really knew how nature ‘interpreted’ these structures. A research team at Cincinnati Children’s Hospital led by Takanori Takebe, MD, reported in Nature that mimicking the 3D shape of the liver was a critical part of making engineered organoids of liver show the same behavior as liver tissue in vivo. These findings show just how important form is for function in nature, bringing us a step closer to alleviating the pressure on organ transplants lists by providing engineering organs.

Not all organs need completely reconstructed replacements. Another critical target organ in the tissue engineering field is the pancreas, which is critical in regulating insulin release.  The nationwide increase in diabetes is only placing more emphasis on finding technologies to augment pancreatic function. Engineers at Duke report in Nature Biomedical Engineering that they could control glucose levels for over a week with a single injection of a new compound they synthesized in the lab.  Rather than many daily injections of insulin for controlling glucose levels in diabetics, this could lead to far less frequent injection.

Machine Diagnosis

We hear quite a bit about Big Data nowadays. This captures a very large field that includes methods to analyze bits of data reliably and quickly to establish patterns (i.e., machine learning) that can help us uncover very new and interesting relationships. Nearly all of this work focuses on narrow data streams, which means the data are largely linked to each other within a category. One example of a narrow data stream is the collection of different types of imaging scans (CT, MRI, PET) from the same patient, collated and compared to better establish how different areas of the brain function. Another example of a narrow data stream is the data contained in a patient’s electronic health record, where it includes facts from the patient’s visits with their physician and specialists.

One interesting thread that is emerging in Big Data is when one starts to cross narrow data streams and create ‘data fabric.’  This means that scientists and engineers are cross-correlating data that seem incompatible with each other, yet they are proving amazingly predictive.  One recent example is when we cross the analysis of speech — one of the earliest machine learning applications — with genetic screening data from patients. Remarkably, scientists at the University of Wisconsin-Madison developed an automated screening system that could analyze audio recordings and determine with 81% accuracy whether the speaker had Fragile X syndrome, a genetic disorder that can have a range of cognitive effects, indicated by genetic screening data. Creating these types of data fabrics could be very powerful in the future because it can use a relatively easy and accessible technology (speech recognition) as an early indicator for more through disease confirmation (genetic testing) and subsequent intervention.

Similarly, these data fabrics are allowing us to reduce our own variability in diagnosing diseases. Penn BE alum Anant Madabhushi developed an algorithm at Case Western Reserve University that was 100% accurate at identifying breast cancer by scanning mammograms, exceeding human performance. Technologies such as these that eliminate the possibility of human error could greatly decrease the rates of delayed or faulty diagnosis. Replacing physicians with computers ? I don’t think so. We all need the human touch, especially when it comes to finding out why we are sick. Capturing errors that humans make? I think so.

A Quick Note

Speaking of Penn alumni, Craig Simmons, Ph.D., who was a postdoctoral fellow in the lab of Penn BE secondary faculty member Peter F. Davies, has been named the interim director of the Institute of Biomaterials & Biomedical Engineering at the University of Toronto. His appointment begins next week. Congratulations to Dr. Simmons!

This Week in BioE (June 22, 2017)

Diversifying the Field

One of the ongoing issues in STEM (science, technology, engineering, and medicine) fields is a lack of diversity among students and faculty. Bioengineering stands out among other engineering fields because it enjoys terrific gender diversity. For example, about half of Penn Bioengineers are women, a feature of our class that goes back decades.

diversifyingHowever, diversity extends well beyond gender. For example, the National Research Mentoring Network (NRMN) has been working to increase diversity, including among students with disabilities. A consortium of people and groups providing mentors for science students, the MRMN recently highlighted the American Association for the Advancement of Science’s (AAAS) Entry Point! program, which focuses on helping students with physical disabilities. Mentoring, it turns out is a big part of helping these students succeed.

Another recent development that should help to increase diversity in the field is the awarding of a $1 million grant from the National Science Foundation’s Directorate of Engineering to the University of Wisconsin, Madison, and the College of Menominee Nation (CMN), a native American college in Wisconsin, to collaborate in engineering research and education. The new grant builds on a program begun in 2010 between the colleges to build labs and facilitate the transfer of pre-engineering students from CMN to UWM.

Brain Science Developments

Speaking of education, three recent news stories discuss how we might be able to expedite the learning process, increase intelligence, and reward ourselves when we create art. In one of the stories, a company called Kernel is investing $100 million in research at the University of Southern California to determine whether using brain implants, which have been helpful in some patients with epilepsy, can be used to increase or recover memory. If successful, this may bridge one critical treatment gap in neurology. About one out of every three people with epilepsy don’t respond to drug treatment.

In the second story, scientists at the University of Texas at Dallas were awarded a $5.8 million contract from DARPA to investigate the role of vagus nerve stimulation in accelerated learning of foreign languages. Stimulating the peripheral nervous system to activate and train areas of the brain is one more example that our nervous system is connected in ways that we do not yet understand completely. The Department of Defense hopes to use the technology to more quickly train intelligence operatives and code breakers.

Finally, in a third story involving the brain, a professor at Drexel University used functional near-infrared spectroscopy to determine which parts of the brain were activated while participants were making art. Dr. Girija Kaimal’s team found that creative endeavors activate the brain’s rewards pathway, as well as elevating the participants’ self-opinion. So making art always made people feel good about themselves; now we know more of the reasons why.

BE Alumni Among Biomaterials Society Leaders

Penn has one of the most distinctive graduate programs in the country, and is proud to graduate the first Ph.D. in Bioengineering in the United States. With such a history, our alumni have succeeded as professors, entrepreneurs, policy leaders, and industry pioneers. One recent example of this Penn tradition  is leadership in national organizations.

At this moment, several faculty in the department (Drs. Susan Margulies, Beth Winkelstein, and Dan Hammer) hold significant positions within the Biomedical Engineering Society (BMES), a cross-cutting national organization for Bioengineering.

Withing the field of biomaterials, the preeminent international organization is the Society for Biomaterials (SfB). Dedicated to the advancement of biomaterials science, the SfB was created more than four decades at nearly the same time the Bioengineering department was established at Penn. Many of our alumni are now part of the senior leadership in the SfB, including the following.

President: David Kohn

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President-elect: Andrés García

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Member-at-large: Helen Lu

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In fact, of the three officers elected this year, two were from Penn (Andrés and Helen).  We also have strong alumni representation across the various committees within the SfB. We extend our congratulations — with great pride — to our Penn family.

Phytoplankton Research Earns Award

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Phytoplankton

The Scripps Institution of Oceanography at the University of California, San Diego, announced last week that one of its faculty members, Andrew Barton, PhD, received a Simons Foundation Early Career Award to study phytoplankton — a type of algae that requires sunlight to survive and that serves as the basis for much of the marine food chain.

Dr. Barton’s research will use the Scripps Plankton Camera System, which provides real-time photographic images to monitor these phytoplankton. While not exactly offering the excitement or cuteness factor of the Golden Retriever Puppy Cam, this sort of technology is incredibly important to better understanding certain aspects of marine biology.

“This is an interesting project that brings cutting edge image-processing technology to the natural habitat to study complex organismal dynamics in the real-world setting,” says Brian Chow, PhD, assistant professor of bioengineering at the University of Pennsylvania. “Establishing the critical interplay between an organism’s form and function and the forces of its local and global environments are important problems in physical biology in general. Diatoms have long been studied by bioengineers interested in self-assembly, programmed assembly, biomineralization, and biomimicry, so the work may lead to some novel insights for our field.”

Congratulations to Dr. Barton on receiving this prestigious award.

Tissue Engineering Makes Spinach Leaf Beat Like a Heart

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Bestill my beating spinach leaf!

One of the more interesting tissue engineering stories to emerge this past month was the successful finding of a team at Worcester Polytechnic Institute (WPI), which used the veins in spinach leaves as a scaffold that was then recellularized with stem cells that produce heart muscle cells. After three weeks, the transplanted cells showed the ability to contract like the heart does when it beats.

“Proper vascularization of artificial living tissues has been one of the most critical challenges of tissue engineering for decades. This is particularly problematic when the size of the engineered tissue increases.,” said Dongeun (Dan) Huh, PhD, Wilf Family Term Assistant Professor in the Department of Bioengineering at the University of Pennsylvania “This work takes an unusual yet ingenious approach to solving this long-standing problem.”

Below you can watch a short video of some of the investigators on the study talking about it.