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!
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.
This week, we present our interview with incoming faculty member Konrad Kording, who starts as a Penn Integrates Knowledge Professor in the Department of Bioengineering and the Department of Neuroscience in the Perelman School of Medicine. Konrad and Andrew Mathis discuss what neuroscience is and isn’t, the “C” word (consciousness), and what it’s like for a native of Germany to live in the United States.
Andrew Tsourkas, Ph.D., who is an associate professor in the Department of Bioengineering, cofounded PolyAurum LLC, a company using gold particles to develop technologies to improve cancer therapies, in 2015. Dr. Tsourkas founded the company with two faculty members from the Perelman School of Medicine: Jay Dorsey, M.D., Ph.D., and Dave Cormode, Ph.D., the latter of whom is also a secondary factory member in BE. The name PolyAurum combines the word polymer with aurum, the Latin word for “gold.” Gold has been found to be able to enhance the effects of radiation therapy in cancer without damaging healthy tissue.
Dr. Tsourkas’s work with his colleagues at PolyAurum was featured recently in the The Philadelphia Inquirer. Debra Travers, the CEO of PolyAurum and herself a cancer survivor, was interviewed by the newspaper for its business section.
According to the article, Drs. Tsourkas and Cormode
have worked to make gold more biocompatible, resulting in PolyAurum’s current technology, Dorsey said. The gold nanocrystals are contained in a biodegradable polymer that allows enough metal to collect in a tumor. The polymer then breaks down, releasing the gold for excretion from the body so that it does not build up in key organs.
This week, we present our interview with incoming faculty member Lukasz Bugaj, who starts as an assistant professor at Penn BE in January. Lukasz and Andrew Mathis discuss tennis and crew, Lukasz’s subfield of optogenetics, and life as the child of a statistician.
Please note: This was our first interview recorded by telephone. We will try to improve the quality of the audio, but for now, be advised that the questions are at a far lower volume than the responses, so set your volume, accordingly, particularly if you are listening on headphones.
Jason Burdick, Ph.D., professor in the Department of Bioengineering, was among the recent recipients of a grant from Sharing Partnership for Innovative Research in Translation (SPIRiT), a pilot grant program awarded by the Clinical and Translational Science Award (CTSA) division of the National Institutes of Health (NIH).
Dr. Burdick’s research, undertaken with Albert Sinusas, MD, of Yale, concerns the development of a noninvasive treatment to limit the damage to the heart caused by heart attacks, which are suffered annually by almost 750,000 Americans. Using single-photo emission computed tomography (SPECT), the technique identifies the damaged heart muscle on the basis of enzymes activated by damage, followed by the targeted administration of bioengineered hydrogels for the delivery of therapeutics
Dr. Burdick says, “This research has the potential to advance treatments for the many individuals with heart attacks who have few current options. Our approach uses injectable materials and advanced imaging techniques to address the changes in protease levels after heart attacks that can lead to tissue damage.”
In other news, Dr. Burdick was one of 12 researchers named by the NIH’s Center for Engineering Complex Tissues to lead collaborative projects aimed at generating complex tissues for several parts of the body.
As we reported earlier, Dan Huh, Wilf Family Term Chair & Assistant Professor in the Department of Bioengineering, has been awarded a $1 million grant from the Cancer Research Institute (CRI), along with its first CRI Technology Impact Award.
Recently, the Penn Engineering Blog featured a story on Dr. Huh’s grant and the research it will support for the next three years. You can read the story at the SEAS blog.
Here’s the promised interview with new faculty member Mike Mitchell, who starts as assistant professor of bioengineering at Penn in the Spring 2017 semester. Mike and editor Andrew E. Mathis discuss Mike’s background and education, where cancer research is now and where it’s heading, and just how big the radius is on the cheesesteak zone of impact around Philadelphia.
Uncertainty is part of life, but the underlying neuroscience of how we make decisions under conditions of uncertainty is only beginning to be understood. In a paper published Monday by Nature Human Behaviour, new Penn Bioengineering faculty member and Penn Integrates Knowledge Professor Konrad Kording, Ph.D., and his coauthor, Iris Vilares, Ph.D., of University College London, offer additional evidence that dopamine lies at the heart of how the brain operates when there is a lack of certainty.
Drs. Kording and Vilares devised a simple computerized test that examined the extent to which test takers relied on previous knowledge vs. what they saw at the present moment. They then administered the test to a cohort of patients with Parkinson’s disease, a condition associated with depleted dopamine levels. The patients were tested both while taking dopaminergic medication and while off it. They found that dopaminergic medication caused the patients to pay greater attention to sensory (i.e., visual) information — an effect that diminished as the patients learned. Ultimately, the study provided evidence that dopamine levels were related to the tendency to rely on new information, also called likelihood uncertainty.
“Scientists believe that understanding uncertainty is key to understanding how the brain computes,” Dr. Kording says. “There are many theories in this space. We provide fairly clean evidence for one of them, which is that dopamine encodes likelihood uncertainty. This information could change the way people think about the manner in which the brain deals with uncertainty.”