The roundworm C. elegans is one of the most important model organisms in biological research. With a transparent, millimeter-long body containing only about a thousand cells and a lifespan of a few weeks, there is no better way of deciphering the role of a given gene on a living creature’s anatomy or behavior. In addition, many of the genes discovered in the worm have been shown to have similar roles in other animals and humans.
In the era of big data, however, a single worm isn’t enough. Thousands upon thousands of individual organisms are necessary to compare many different genes and ensure the reliability of experimental results.
Engineers at the University of Pennsylvania have taken strides to make this type of high-throughput experiment feasible by developing a system they have dubbed “the WorMotel.” To demonstrate its effectiveness, the researchers have studied the role of a set of mutations and stress-inducing drugs on the aging of 1,935 of these organisms, specifically, what percentage of their lifespans they remain healthy and active.
The WorMotel system features index-card-sized plates made out of a transparent polymer. Each plate features 240 individual wells, in which a single worm lives its entire life. Automated systems keep them fed and stimulated while machine vision algorithms track and record their behavior.
The WorMotel system is also designed to be highly scalable. Robotic carousels can automatically swap hundreds of WorMotel plates in and out of analysis chambers, studying up to 57,600 worms in a single experiment.
The study, published in the journal eLife, was led by Christopher Fang-Yen, Wilf Family Term Assistant Professor in Bioengineering in Penn’s School of Engineering and Applied Science, and Matthew Churgin, a former graduate student (now a postdoctoral fellow) in his lab. They collaborated with David Raizen, an Associate Professor of Neurology in Penn’s Perelman School of Medicine. Former Fang-Yen lab members Sang-Kyu Jung, Chih-Chieh (Jay) Yu, and Xiangmei Chen also contributed to the research.
Continuing with our series of interviews with new faculty members, we feature this interview with Dr. Joel Boerckel, who has a dual appointment in the Department of Bioengineering at Penn and the Perelman School of Medicine’s Department of Orthopaedic Surgery. Dr. Boerckel’s research concerns the mechanobiology of development and regeneration. Here, he speaks with Andrew Mathis about his career to this point and where he sees the fields of tissue engineering and regenerative medicine heading over the future. Enjoy!
Excessive exposure to the sun remains a leading cause of skin cancers. The common methods of protection, including sunscreens and clothing, are the main ways in which people practice prevention. Amazingly, new research shows that what we eat could affect our cancer risk from sun exposure as well. Joseph S. Takahashi, Ph.D., who is chair of the Department of Neuroscience at the University of Texas Southwestern Medical Center’s Peter O’Donnell Jr. Brain Institute, was one of a team of scientists who recently published a paper in Cell Reports that found that by restricting the times when animals ate, their relative risk from exposure to ultraviolet light could change dramatically.
We tend to think of circadian rhythms as being among the reasons why we get sleepy at night, but the skin has a circadian clock as well, and this clock regulates the expression of certain genes by the epidermis, the visible outermost layer of the skin. The Cell Reports study found that food intake also affected these changes in gene expression. Restricting the eating to time windows throughout a 24h cycle, rather than providing food all the time, led to reduced levels of a skin enzyme that repairs damaged DNA — the underlying cause of sun-induced skin cancer. The study was conducted in mice, so no firm conclusions about the effects in humans can be drawn yet, but avoiding midnight snacks could be beneficial to more than your weight.
Let’s Get Small
Nanotechnology is one of the most common buzzwords nowadays in engineering, and the possible applications in health are enormous. For example, using tiny particles to interfere with the cancer signaling could give us a tool to stop cancer progression far earlier than what is possible today. One of the most recent approaches is the use of star-shaped gold particles — gold nanostars — in combination with an antibody-based therapy to treat cancer.
The study authors, led by Tuan Vo-Dinh, Ph.D., the R. Eugene and Susie E. Goodson Professor of Biomedical Engineering at Duke, combined the gold nanostars with anti-PD-L1 antibodies. The antibodies target a protein that is expressed in a variety of cancer types. Focusing a laser on the gold nanostars heats up the particles, destroying the cancer cells bound to the nanoparticles. Unlike past nanoparticle designs, the star shape concentrate the energy from the laser at their tips, thus requiring less exposure to the laser. Studies using the nanostar technology in mice showed a significant improvement in the cure rate from primary and metastatic tumors, and a resistance to cancer when it was reintroduced months later.
Nanotechnology is not the only new frontier for cancer therapies. One very interesting area is using plant viruses as a platform to attack cancers. Plant viruses stimulate a natural response to fight tumor progression, and these are viewed by some as ‘nature’s nanoparticles’. The viruses are complex structures, and offer the possibility of genetic manipulation to make them even more effective in the future. At Case Western Reserve University, scientists led by Nicole Steinmetz, Ph.D., associate professor of biomedical engineering, used a virus that normally affects potatoes to deliver cancer drugs in mice. Reporting their findings in Nano Letters, the authors used potato virus X (PVX) to form nanoparticles that they injected into the tumors of mice with melanoma, alongside a widely used chemotherapy drug, doxorubicin. Tumor progression was halted. Most importantly, the co-administration of drug and virus was more effective than packing the drug in the virus before injection. This co-administration approach is different than past studies that focus on packaging the drug into the nanoparticle first, and represents an important shift in the field.
Educating Engineers “Humanely”
Engineering curricula are nothing if not rigorous, and that level of rigor doesn’t leave much room for education in the humanities and social sciences. However, at Wake Forest University, an initiative led by founding dean of engineering Olga Pierrakos, Ph.D., will have 50 undergraduate engineering students enrolled in a new program at the college’s Downtown campus in Winston-Salem, N.C. The new curriculum plans for an equal distribution of general education/free electives relative to engineering coursework, with the expectation that the expansion of the liberal arts into and engineering degree will develop students with a broader perspective on how engineering can shape society.
People in the News
At the University of Illinois, Urbana-Champaign, Rashid Bashir, Ph.D., Grainger Distinguished Chair in Engineering and professor in the Department of Bioengineering, has been elevated to the position of executive associate dean and chief diversity officer at UIUC’s new Carle Illinois College of Medicine. The position began last week. Professor Michael Insana, Ph.D., replaces Dr. Bashir as department chair.
At the University of Virginia, Jeffrey W. Holmes, Ph.D., professor of biomedical engineering and medicine, will serve as the director of a new Center for Engineering in Medicine (CEM). The center is to be built using $10 million in funding over the next five years. The goal of the center is to increase the collaborations among engineers, physicians, nursing professionals, and biomedical scientists.
In the aftermath of the presidential election, quite a few experts cited the lack of economic opportunity for many as a primary factor that elevated Donald Trump to the presidency. These changes in economic opportunity did not occur months prior to the election, but they resulted from years of continual changes in the US economy.
For example, manufacturing represented more than 50% of the economic output and jobs after World War II; it now represents only 10% of the economy. Professional services — in finance, health, insurance, education, and similar industries — represented less than 5% of the economy in 1950, while it now captures almost 40% of the economy. Our country went from makers to providers. Many other workplace traditions have also changed; e.g., one often doesn’t work for the same employer for decades, nor do workers have confidence that they will remain in the career they start in their 20s. A physician could become a business owner and then (if we are lucky) a teacher. These changes are causing many of us to ask: What should we be teaching our students for this future?
First, let’s understand how economies can change. One theory in economics puts these job sector shifts as part of Kondriateff waves, which pass through the US economy in (roughly) 50- to 80-year cycles. These “K-waves” reach back to late 18th century and continue to the current day. The economist Joseph Schumpeter reasoned that these waves were triggered by technological revolutions; e.g., the invention of the steam engine and new steel production processes led to a K-wave from 1850 to 1900 that included the development of the railroad system, the settling of the American West, and the emergence of the American economy as a global force. Similarly, the widespread availability of consumer computer power and the invention of the Internet in the late 20th century created a K-wave that began in 1990 and is cresting now with the emergence of alternative media (e.g., cutting the digital cord with online media access), the Internet of Things, and the Big Data wave.
Where Engineers Fit In
As engineers, we are naturally attracted to the idea that technology starts the wave that affects everything else. But this belief raises a question: If technology triggers waves, then how can we predict where the next wave will start? And a second question follows: How do we organize and educate ourselves so that we make the most of these technologies so society can ride this wave effectively, rather than absorb the displacements these waves create? Well, we all know it is hard to predict the future. However, a recent report from the Brookings Institute helps us pinpoint areas of the economy that are most powerful in creating downstream economic output, whether it is additional jobs, more exports, or the forming of completely new industries. Given their potency, it is likely that new economic opportunities will emerge more frequently from this sector than any other.
Rather than using the traditional categorization scheme that breaks up the economy into bins associated with worker output (e.g., we manufacture, provide financial services, trade energy goods, supply food), the Brookings report asked a slightly different question: Which parts of the economy provide the downstream spark for the rest of us? If we understood the origin of this spark, we would be much more informed about how to make strategic investments that will have broad economic trickle-down effects on the national economy. The answer? The most potent part of our economy consists of the industries that invest heavily in research and development and contain a high percentage of employees with STEM degrees. The Brookings report termed these advanced industries. And this part of the economy is indeed potent. It generates 2.7 additional downstream jobs for every job in this sector, far outpacing the highly publicized downstream impact of the manufacturing sector (1.7 downstream jobs per manufacturing job). Advanced industries contain 8% of the workforce but generate 19% of the national GDP, and advanced industries span everything from communications, defense, and security to health, medicine, and the environment.
Creating Economic Opportunity Waves
Knowing that this is the proverbial spark certainly places a premium on educating scientists and engineers and placing them in these advanced industries. Some of them could become the next Elon Musk, a Penn alum (SAS ’97) whose vision will eventually electrify the entire fleet of motor vehicles in the US. Others could follow in the footsteps of Carl June, MD, a Penn faculty member who invented a radically new form of cancer immunotherapy that may be the biggest change in cancer treatment in several decades. But what can colleges and universities teach students today to make them thrive in the epicenters of these advanced industries? How can we teach so that our students are ahead of the curve and, in some cases, creating these curves?
We are constantly discussing the content of undergraduate and graduate education here at Penn. In these conversations, it is often easy to fall into the trap of saying “Well, I can’t imagine a degree in X not having a course in Y” or “If I had to learn X, then my students should learn X too.” I think we should step away from specific courses and distribution sequences for a moment and think about the core principles in an engineering education that will allow our graduates to successfully navigate any economic wave that falls across all of us. In the most successful form, we would educate people that successfully create waves to benefit everyone. I suggest focusing on three core principles in an undergraduate’s engineering education toward achieving this goal.
Introduce the uncertainty of researchto counterbalance the certainty of formal didactic instruction. For engineering, teaching the fundamentals makes the world a safer place, whether we are teaching safety factors, repeatability, or design standards. But the advanced industries are at the bleeding edge of uncovering knowledge not in textbooks. And this new knowledge eventually creates something useful and interesting. Yet there is always a major transition for students when they realize that technological advances never come from a script in a textbook. Many will ask, “How can I learn anything that isn’t known?” Historically, we would use undergraduate education to teach what is known, and graduate education to answer the unknown. But if creating new ideas in advanced industries requires one to determine some of the unknowns, we shouldn’t restrict research experiences to just graduate education anymore.
Research forces one to learn the inexact science of breaking down a complex problem into more manageable parts, finding out which of these parts is most critical in solving the problem, and the finding a solution. Research uses failure as a mechanism to learn, and teaches persistence and patience. These are good things to learn if you want to be in industries that are searching for the Next Big Idea. In many ways, research experiences resemble learning a foreign language — the first language (research experience) is a real bear, but they get easier as you learn more of them (additional experiences). Jumping across different fields would parallel the learning of more than one foreign language and would be a good primer for a career in the advanced industries. If more of us became comfortable with uncertainty and failure, we would accelerate the creation and filtering of new ideas and products, in turn creating more opportunities for everyone in the economy.
Teach invention, as it will continue to drive economic development. Over a decade ago, the American university system was recognized for its almost unique ability to educate students who would thrive as innovators over their careers. American higher education was sought after by students around the world, and world universities started to tweak their own models of education, inspired by the US success story. Much of what was written about the ‘secret sauce’ for American higher education was the magical ingredient of innovation that existed on college campuses in the US. However, we are overlooking the one critical ingredient upstream of innovation that makes the innovation engine go: inventing new ideas. So much activity surrounding innovation involves how to package ideas for marketplace needs or how to use marketplace needs to filter through existing technologies to create new products.Our science and engineering infrastructure is driven by inventing technologies and algorithms that appear years to decades later in innovative products. And we are sorely overlooking how to best educate to invent, e.g., the classroom environment that forms the best ideas, or the best methods to teach the abstraction of several seemingly unrelated problems into a common group of invention challenges that will serve hundreds of innovations. Just as philosophy class in college can shape people’s views of morality for the rest of their lives, the practical experience of conceiving and executing a new idea for a market can leave a lifelong impression on a college student for seeing and creating opportunity in the world. Many students graduate nowadays with a much better idea about how to take ideas and commercialize them into products. Adding the teaching of invention will replenish the ideas that feed the future of these innovation pipelines.
Include the economists, artists, and philosophers. Jason Silva has a wonderful quote about engineering: “The scientist and engineers who are building the future need the poets to make sense of it.” I couldn’t agree more. Artists and philosophers have an interesting reflection role in society, whether it is to challenge one’s perception of the ordinary or to make the ordinary unusual (artist) or to provide a more holistic view of a human’s purpose (philosopher). Likewise, economists can explain how technology can drive development locally and globally and the subsequent changes expected in the workforce. In other words, they all provide different optics on the same idea.
Engineering may enjoy a sterling reputation as creating a world that others do not see, but we are sometimes too enamored with this vision to ask a very simple question: If we can do it, should we do it? Technologists can cite several inventions in the past as drivers of economic change that pushed society forward (see K-waves, above) and never backward. The mechanization of the agriculture industry coincided with the emergence of manufacturing and heavy industries in the US and elsewhere in the 19th century, and this advanced the world. People moved from working on farms to working in factories, and the urbanization movement swept across the country. In a similar manner, artificial intelligence could cause a similar shift in the services sector today and create a supply of highly educated people to tackle the world’s next big problem. For this reason, they can help engineers understand the impact of their ideas even before they are implemented.
Creating new technologies without a thoughtful mulling about how they could really change the world seems irresponsible to me, given how some of these technologies could completely change large parts of the economic landscape quickly. And it could lead to other societal crises — e.g., do we really want to interrupt nature’s evolutionary clock without considering the impact of editing our own genome? Similar questions exist when we start to understand how our minds work and the principles by which we can (and should) study and influence the human traits of identity, reasoning, and self. One of our faculty recently wrote about the ethical constructs by which we should view these advances in understanding how we think, and how they can influence the science of mind control. Broadly speaking, initiating these conversations in advance will help engineers realize that these technologies should not be created in a vacuum, and they must be developed in parallel with conversations about the impact of their use.
A Mirror, Not a Trigger
All of this brings us back to the beginning. The election wasn’t the trigger but the mirror, and we must answer the call to think about engineering education to create future economic opportunity instead of passively watching it happen. We now know that advanced industries are the most powerful part of our economy for generating downstream economic output. We are fortunate that engineers are a central part of these industries. And we now know the dramatic changes in the demographics of opportunity among the electorate that occurred in the past two decades. By re-emphasizing core principles to impress upon our engineering students, we can be part of a future that focuses more on opportunities for the society rather than the individual. And we can use this new mindset to tackle some of the most pressing problems we see in front of us (e.g., affordable health care, energy, climate change) and those problems that we don’t see yet.
Pancreatic cancer remains one of the deadliest types of cancer, with one- and five-year survival rates of only 20% and 7%, respectively, according to the American Cancer Society. The mortality is so high because the disease does not typically cause symptoms until it is too late. Therefore, earlier detection could be the key to better survival rates.
In a new paper published by Lab on a Chip, a research team from the lab of David Issadore, assistant professor of Bioengineering, reports on its development of a micropore chip, callled the circulating tumor cell fluorescence in situ hybridization (CaTCh FISH) chip, that could detect circulating tumor cells (CTCs) from mice and patients with pancreatic cancer, even at very low, previously undetectable levels.
Jin A (Jina) Ko, who is a Ph.D. student in Bioengineering and first author on the paper, says that CTCs are a key mechanism underlying metastasis, which is another reason why pancreatic cancer has such a low survival rate. Not only can the chip that she helped design detect these cells, which circulate in the bloodstream, but more importantly, pancreatic tumors shed these cells even in their very early stages before any spread has occurred. Therefore, provided the test is performed early enough, the tumor can be detected and treated. Patients with family histories of pancreatic cancer or who have tested positive for certain gene mutations would likely benefit from this sort of test.
The study authors also tested the CaTCh FISH chip using blood samples from 14 patients with advanced pancreatic cancer and from healthy controls. They found that their micropore chip could detect several RNA markers of cancer in 10-mL samples — around 2 tsp. In addition, there were no false-negative results among the healthy controls, demonstrating a high level of reliability in that regard.
“We have developed a microchip platform that combines fast, magnetic micropore-based negative immunomagnetic selection with rapid on-chip in situ RNA profiling,” Jina said. “This integrated chip can isolate both rare circulating cells and cell clusters directly from whole blood and allow individual cells to be profiled for multiple RNA cancer biomarkers.”
Megan Sperry, a Ph.D. student in the Department of Bioengineering, is a recipient of a Student Design and Research Award from the Biomedical Engineering Society (BMES). Megan works in the Spine Pain Research Lab of Beth Winkelstein, Ph.D., professor of Bioengineering and Vice Provost for Education at Penn’s School of Engineering and Applied Science, as well as with Eric Granquist, DMD, MD, an oral and maxillofacial surgeon at Penn Dental Medicine.
With Drs. Winkelstein and Granquist, Megan studies temporomandibular joint (TMJ) pain and osteoarthritis, the latter of which can develop as a long-term consequence of untreated TMJ dysfunction. There’s currently no way to determine which patients will progress to TMJ osteoarthritis, so Megan’s extended abstract, which was submitted to the BMES competition, detailed a study using 18F-EF5 PET, an imaging modality used mainly in oncology. Hypothesizing that hypoxia, or low oxygen, was a key factor in the development of TMJ osteoarthritis, Megan studied the relationship between hypoxia and persistent TMJ pain and found that hypoxia preceded reorganization of the cartilage of the TMJ, part of the process culminating in TMJ osteoarthritis (see image below).
“This project has been both fun and challenging because it brings together concepts and techniques from multiple fields, including orthopedics, neuroscience, and, with the use of 18F-EF5, radiation oncology,” Megan said. “I’m excited to have the opportunity to share my work at the BMES Annual Meeting and receive feedback as we continue to move the project forward.”
Each year, BMES awards up to five graduate students the Student Design and Research Award from dozens of submissions. Congratulations to Megan for this elite recognition of her research!
Synthetic biology (SynBio) is an important field within bioengineering. Now, SynBio and its relationships with nanotechnology and microbiology will get a big boost with a $6 million grant from the National Science Foundation awarded to the lab of Jason Gleghorn, Ph.D., assistant professor of biomedical engineering at the University of Delaware. The grant, which comes from the NSF’s Established Program to Stimulate Competitive Research, will fund research to determine the interactions between a single virus and single microbe, using microfluidics technology so that the lab staff can examine the interactions in tiny droplets of fluid, rather than using pipettes and test tubes. They believe their research could impact healthcare broadly, as well as perhaps help agriculture by increasing crop yields.
While must SynBio research is medical, the technology is now also being used in making commercial products that will compete with other natural or chemically synthesized products. Antony Evans’s company Taxa Biotechnologies has developed a fragrant moss that he hopes can compete against the sprays and other chemicals you see on the store shelves. Using SynBio principles, Taxa isolates the gene in plants causing odor and transplants these genes to a simple moss in a glass terrarium that, with sufficient sunlight, water, carbon dioxide, will provide one of three scents completely naturally. Technically, the mosses are genetically modified organisms (GMOs), but since people aren’t eating them, they aren’t likely to generate the controversy raised by GMO foods. Taxa has also been working on transplanting bioluminescence genes to plants to provide light without requiring electricity, all as a part of a larger green campaign.
A Few Good Brains
A division of the U.S. Department of Defense, the Targeted Neuroplasticity Training (TNT) program of the Defense Advanced Research Projects Agency (DARPA) will fund the research of Stephen Helms Tillery, Ph.D., of the School of Biological & Health Systems Engineering at Arizona State University, who is investigating methods of enhancing cognitive performance using external stimulation. The ASU project is using transdermal electrical neuromodulation to apply electrical stimulation via electrodes placed on the scalp to determine the effects on awareness and concentration. DARPA hopes to obtain insight into how to improve decision making among troops who are actively deployed. The high-stress environment of a military deployment, combined with the fact that soldiers tend to get suboptimal amounts of sleep, leaves them with fatigue that can cloud judgment in moments of life or death. If the DARPA can find a way to alleviate that fatigue and clarify decision-making processes, it would likely save lives.
End-stage organ failure can be treated by transplantation, but waiting lists are long and the number of donors still insufficient, so alternatives are continually sought. In the field of regenerative medicine, which is partly dedicated to finding alternatives, scientists at Ohio State have developed a technology called tissue nanotransfection, which can generate any cell type within a patient’s own body. In a paper published in Nature Nanotechnology, professors Chandan Sen and James Lee and their research team describe how they used nanochip technology to reprogram skin cells into vascular cells. After injecting these cells into the injured legs and brains of mice and pigs, they found the cells could help to restore blood flow. The applications to organ systems is potentially limitless.
For cardiac patients whose conditions can be treated without need for a transplant, who make up the vast majority of this cohort, stents and valve prostheses are crucial tools. However, these devices and the procedures to implant them have high complication rates. Currently, patients receiving prosthetic valves made in part of metal must take blood thinners to prevent clots, and these drugs can greatly diminish quality of life and limit activity, particularly in younger patients. At Cornell, Jonathan Butcher, Ph.D., associate professor of biomedical engineering, is developing a prosthetic heart valve with small niches in the material loaded with biomaterials to maintain normal heart function and prevent clotting. While it has been possible for some time to coat the surface of an implant with a drug or chemical to facilitate its integration and function, these niches allow for a larger depot of such a material to be distributed over a longer period of time, increasing the durability of the positive effects of these procedures.
A number of medical diagnoses are accomplished by testing of bodily fluids, and spectrometry is a key technology in this process. However, spectrometers are expensive and usually not very portable, posing a challenge for health professionals working outside of traditional care settings. Now, a team led by Brian Cunningham, Ph.D., from the University of Illinois, Urbana-Champaign, has published in Lab on a Chipa paper detailing their creation of a smartphone-integrated spectroscope. Called the spectral Transmission-Reflectance-Intensity (TRI)-Analyzer, it uses microfluidics technology to provide point-of-care analysis to facilitate treatment decisions. The authors liken it to a Swiss army knife in terms of versatility and stress that the TRI Analyzer is less a specialized device than a mobile laboratory. The device costs $550, which is several times less than common lab-based instruments.
New Chair at Stanford
Stanford’s Department of Bioengineering has announced that Jennifer Cochran, Ph.D., will begin a five-year term as department chair beginning on September 1. Dr. Cochran arrived at Stanford in 2005 after earning degrees at the University of Delaware and MIT. Cochran has two connections to Penn – she is currently serving as a member of our department advisory board and completed her postdoctoral training in Penn Medicine. Our heartiest congratulations to her!
The chapter of the Biomedical Engineering Society (BMES) at the University of Pennsylvania has won the Student Outreach Achievement Award from the society. This is the second time in three years that BMES at Penn has won the award, for which more than 60 other chapters compete.
The award acknowledges the efforts of Penn BMES to establish relationships with the surrounding community. For instance, Junior Beta Day, held in the spring semester, saw Penn BE students hosting approximately 60 local middle school students for a day on campus, during which they interacted with members of the faculty and engaged in activities centered on bioengineering. In addition, the Penn BMES chapter has participated in local neighborhood revitalization initiatives and acted as mentors.
“I’m very proud of our group’s outreach initiatives within the both the greater Philadelphia and campus communities,” said Sonia Bansal, who is one of the outreach chairs for the chapter. “Our partnerships with iPraxis and SPARK help us break down bioengineering concepts into approachable activities for middle school students. We hope that our programming shows students that they too can go on to be engineers and scientists, and its an incredibly rewarding experience to see students get excited about STEM.”
Founded in 1968, BMES is a 501(c)(3) nonprofit professional association acting as a lead society for 7,000 members and 115 student chapters.
Organ transplantation is a lifesaving measure for people with diseases of the heart, lungs, liver, and kidneys that can no longer be treated medically or surgically. The United Network for Organ Sharing, a major advocacy group for transplant recipients, reports that a new person is added to a transplant list somewhere in America every 10 minutes. However, rejection of the donor organ by the recipient’s immune system remains a major hurdle for making every transplant procedure successful. Unfortunately, the drugs required to prevent rejection have serious side effects.
To address this problem, a research team at Cornell combined DNA sequencing and informatics algorithms to identify rejection earlier in the process, making earlier intervention more likely. The team, led by Iwijn De Vlaminck of the Department of Biomedical Engineering, report in PLOS Computational Biology that a computer algorithm they developed to detect donor-derived cell-free DNA, a type of DNA shed by dead cells, in the blood of the recipient could predict heart and lung allograft rejection with a 99% correlation with the current gold standard. The earlier that signs of rejection are detected, the more likely it is that an intervention can be performed to save the organ and, more importantly, the patient.
Meanwhile, at Yale, scientists have used nanoparticles to fight transplant rejection. Publishing their findings in Nature Communications, the study authors, led by Jordan S. Pober, Bayer Professor of Translational Medicine at Yale, and Mark Saltzman, Goizueta Foundation Professor of Chemical and Biomedical Engineering, used small-interfering RNA (siRNA) to “hide” donated tissue from the immune system of the recipient. Although the ability of siRNA to hide tissue in this manner has been known for some time, the effect did not last long in the body. The Yale team used poly(amine-co-ester) nanoparticles to deliver the siRNA that extended and extended its duration of effect, in addition to developing methods to deliver to siRNA to the tissue before transplantation. The technology has yet to be tested in humans, but provides an exciting new approach to help solve the transplant rejection challenge in medicine.
Africa in Focus
A group of engineering students at Wright State University, led by Thomas N. Hangartner, professor emeritus of biomedical engineering, medicine and physics, traveled to Malawi, a small nation in southern Africa, to build a digital X-ray system at Ludzi Community Hospital. Once on site, Hangartner and his student team trained the staff to use system on patients. The group hopes they have made a significant contribution to improving the standard of care in the country, which currently allocates only 9% of its annual budget to healthcare. While the project admitted has limited impact, it’s important to bear in mind that expanding public health on a global level is a game of inches. The developing world will rise to the standards of the developed world one village at a time, one hospital at a time.
Speaking of Africa, the recent Ebola outbreak in West Africa had global implications and prompted many international organizations to identify better methods to identify early signs of outbreak. Since diseases like Ebola can spread rapidly and aggressively, detecting the outbreak early can save thousands of lives. To this end, Tony Hu of Arizona State University’s School of Biological and Health Systems Engineering has partnered with the U.S. Army to develop a platform using porous silicone nanodisks that, coupled with a mass spectrometer, could be used to detect Ebola more quickly and less expensively. In particular, by determining the strain of the Ebola virus detected, treatment could be more specifically individualized for the patient. Dr. Hu presents the technology in a video available here.
Karen Moxon, professor of biomedical and mechanical engineering at the University of California, Davis, recently showed that rats with spinal injuries recovered to a more significant extent when treated with a combination of serotonergic drugs and physical therapy. Dr. Moxon found that the treatment resulted in cortical reorganization to bypass the injury. Many consider combining two different drugs to treat a disease or injury; Moxon’s clever approach used a drug in combination with the activation of cortical circuits (electroceuticals), and approach that was not considered possible with some types of spinal cord injuries.
At Stanford, Karl Deisseroth, professor of bioengineering and of psychiatry and behavioral sciences, led a study team that recently reported in Science Translational Medicine that mice bred to have a type of autism could receive a genetic therapy that caused their brain cells to activate differently. Although the brains of the autistic mice were technically normal, the mice were unsocial and lacked curiosity. Treatment modulated expression of the CNTNAP2 gene, resulting in increased sociability and curiosity. Their findings could have tremendous implications for treating autism in humans.
Elsewhere in neurotech, Cornell announced its intention to create a neurotech research hub, using a $9 million grant from the National Science Foundation. Specializing in types of neurological imaging, the new NeuroNex Hub and Laboratory for Innovative Neurotechnology will augment the neurotech program founded at Cornell in 2015.
Two important B(M)E department have developed new programs. In Montreal, McGill University has introduced a graduate certificate program in translational biomedical engineering (video here). Also at the annual meeting of the American Society for Engineering Education in Columbus, Ohio, an interdisciplinary group of scholars from Worcester Polytechnic Institute, including three professors of engineering, presented a paper entitled “The Theatre of Humanitarian Engineering.” The authors developed an experimental role-playing course in which the students developed a waste management solution for a city. According to the paper’s abstract, a core misunderstanding about engineering is the belief that it exists separately from social and political contexts. With the approach they detail, the authors believe they could address the largely unmet call for greater integration of engineering with the humanities and social sciences on the academic level.
The vast majority of genetic mutations that are associated with disease occur at sites in the genome that aren’t genes. These sequences of DNA don’t code for proteins themselves, but provide an additional layer of instructions that determine if and when particular genes are expressed. Researchers are only beginning to understand how the non-coding regions of the genome influence gene expression and might be disrupted in disease.
Jennifer Phillips-Cremins, assistant professor in the Department of Bioengineering in the University of Pennsylvania’s School of Engineering and Applied Science, studies the three-dimensional folding of the genome and the role it plays in brain development. When a stretch of DNA folds, it creates a higher-order structure called a looping interaction, or “loop.” In doing so, it brings non-coding sites into physical contact with their target genes, precisely regulating gene expression in space and time during development.
Phillips-Cremins and lab member Jonathan Beagan have led a new study identifying a new protein that connects loops in embryonic stem cells as they begin to differentiate into types of neurons. Though the study was conducted in mice, these findings inform aspects of human brain development, including how the genetic material folds in the 3-D nucleus and is reconfigured as stem cells become specialized. Better understanding of these mechanisms may be relevant to a wide range of neurodevelopmental disorders.
Cremins lab members Michael Duong, Katelyn Titus, Linda Zhou, Zhendong Cao, Jingjing Ma, Caroline Lachanski and Daniel Gillis also contributed to the study, which was published in the journal Genome Research.