Phillips-Cremins Research Identifies Protein Involved in Brain Development

Phillips-Cremins
Jennifer Phillips-Cremins, Ph.D.

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.​​​​​​

Continue reading at the SEAS blog.

New Faculty: Interview With Konrad Kording

Kording
Konrad Kording, PhD

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.

 

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Week in BioE (August 3, 2017)

There’s news in bioengineering every week, to be sure, but the big story this past week is one that’s sure to continue appearing in headlines for days, weeks, and months — if not years — to come. This story is CRISPR-Cas9, or CRISPR for short, the gene-editing technology that many geneticists are viewing as the wave of the future in terms of the diagnosis and treatment of genetic disorders.

Standing for clustered regularly interspaced short palindromic repeats, CRISPR offers the ability to cut a cell’s genome at a predetermined location and remove and replace genes at this location. As a result, if the location is one at which the genes code for a particular disease, these genes can be edited out and replaced with healthy ones. Obviously, the implCRISPRications for this technology are enormous.

This week, it was reported that, for the first time, CRISPR was successfully used by scientists to edit the genomes of human embryos. As detailed in a paper published in Nature, these scientists edited the genomes of 50 single-cell embryos, which were subsequently allowed to undergo division until the three-day mark, at which point the multiple cells in the embryos were assessed to see whether the edits had been replicated in the new cells.  In 72% of them, they had been.

In this particular case, the gene edited out was one for a type of congenital heart defect, and the embryos were created from the eggs of healthy women and the sperm of men carrying the gene for the defect. However, the experiments prove that the technology could now be applied in other disorders.

Needless to say, the coverage of this science story has been enormous, so here is a collection of links to coverage on the topic. Enjoy!

Tsourkas Joint Venture Featured in “Inquirer”

Tsourkas
Andrew Tsourkas, Ph.D.

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.

Read more at the Inquirer Web site.

New Faculty: Interview With Lukasz Bugaj

Bugaj
Lukasz Bugaj, Ph.D.

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.

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Week in BioE (July 27, 2017)

The Brain in Focus

BrainAt Caltech, scientists are exploiting the information generated by body movements, determining how the brain codes these movements in the anterior intraparietal cortex — a part of the brain beneath the top of the skull. In a paper published in Neuron, Richard A. Andersen, James G. Boswell Professor of Neuroscience at Caltech, and his team tested how this region coded body side, body part, and cognitive strategy, i.e., intention to move vs. actual movement. They were able determine specific neuron groups activated by different movements. With this knowledge, more effective prosthetics for people experiencing limb paralysis or other kinds of neurodegenerative conditions could benefit enormously.

Elsewhere in brain science, findings of chronic traumatic encephalopathy in football players have raised significant controversy. Seeking to better understand head impact exposure in young football players, scientists from Wake Forest University led by biomedical engineer Joel D. Stitzel, fitted athletes with telemetric devices and collected four years of data and more than 40,000 impacts. They report in the Journal of Neurotrauma that, while all players experienced more high magnitude impacts during games compared to practices, younger football players experienced a greater number of such impacts during practices than the other groups, and older players experienced a greater number during actual games. The authors believe their data could contribute to better decision-making in the prevention of football-related head injuries.

Up in Canada, a pair of McGill University researchers in the Department of Neurology and Neurosurgery — Professor Christopher Pack and Dave Liu, a grad student in Dr. Pack’s lab — found that neuroplasticity might apply to more parts of the brain than previously thought. They report in Neuron that the middle temporal area of the brain, which contributes to motion discrimination and can be inactivated by certain drugs, could become relatively impervious to such inactivation if pretrained. Their findings could have impacts on both prevention of and cures for certain types of brain injury. 

The Virtues of Shellfish

If you’ve ever had a diagnostic test performed at the doctor’s office, you’ve had your specimen submitted to bioassay, a test in which living cells or tissue is used to test the sampled material. University of Washington bioengineer Xiaohu Gao and his colleagues used polydopamine, an enzyme occurring in shellfish, to increase the sensitivity of bioassays by orders of magnitude. As reported in Nature Biomedical Engineering, they tested the technology, called enzyme-accelerated signal enhancement (EASE), in HIV detection, finding that it was able to help bioassays identify the virus in tiny amounts. This advance could lead to earlier diagnosis of HIV, as well as other conditions.

Mussels are also contributing to the development of new bioadhesives. Julie Liu, associate professor of chemical engineering at Purdue, modeled an elastin-like polypeptide after a substance produced naturally by mussels, reporting her findings in Biomaterials. With slight materials, Dr. Liu and her colleagues produced a biomaterial with moderate adhesive strength that demonstrated the greatest strength yet among these materials when tested under water. The authors hope to develop a “smart” underwater adhesive for medical and other applications.

Science in Motion

Discussions of alternative forms of energy have focused on the big picture, such as alleviating our dependence on fossil fuels with renewable forms of energy, like the sun and wind. On a much smaller level, however, engineers are finding smaller energy sources — specifically people.

Reporting in ACS Energy Letters, a research team led by Vanderbilt’s Cary Pint, assistant professor in the Department of Mechanical Engineering and head of Vanderbilt’s Nanomaterials and Energy Devices Laboratory Nanomaterials and Energy Devices Laboratory, designed a battery in the form of an ultrathin black phosphorous device that can generate electricity as it is bent. Dr. Pint describes the device in a video here. Although it can’t yet power an iPhone, the possibility isn’t far away.

Moving Up

Two BE/BME departments have named new chairs. At the University of Utah, David Grainger, who previously chaired the Department of Pharmaceutics and Pharmaceutical Chemistry, will become chair of the Department of Bioengineering. Closer to home, Michael I. Miller became the new chair of the Department of Biomedical Engineering on July 1. Congratulations to them both!

Burdick Recognized by NIH in Two Programs

Burdick
Jason Burdick, Ph.D.

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.

Organ-on-a-Chip Earns Big CRI Grant for Huh Lab

CRI grant Huh
Dan Huh, Ph.D.

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.

Congratulations again to Dr. Huh!

New Faculty: Interview With Mike Mitchell

Mitchell
Mike Mitchell, Ph.D.

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.

Enjoy!

Secondary Projects From Ghana: Group 4

While brainstorming and writing a proposal for a device to detect pediatric tuberculosis has been extremely valuable, we recognize the challenge of developing our devices as undergraduate/graduate students. This acknowledgement led us to try to identify a healthcare problem in Ghana and to come up with a solution that undergraduates could potentially pursue. The process began after we arrived in Ghana, with each student independently identifying a problem and brainstorming a solution. Next, we played an entrepreneurial game, in which each student gave a pitch for an idea, and everyone gave hypothetical money to his or her favorite idea. The ideas with the most hypothetical monetary investments would move on to the next round. After two rounds of pitches, we narrowed our list down to two ideas: Big Data and the Multi-Cot. Splitting up our group between the two ideas, we then prepared a presentation to give to Kumasi Center for Collaborative Research in Tropical Medicine (KCCR) researchers. Yesterday and today, we present the summaries of our ideas.

Ghana group 4-1
The Multi-Cot aims to tackle the issue of limited space in large regional hospitals within Ghana and other similar situations of overcrowding.

Kate Panzer (gave first-round pitch) ’18, Katharine Cocherl ’20, Kaila Helm ’20, Hope McMahon ’18

Throughout our time in Ghana, we had the opportunity to visit many hospitals and smaller health clinics. While visiting Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana, we noticed that there was a poster on a pediatrician’s wall for the “One Baby One Cot” initiative. We soon learned that there is very limited space per patient at the large regional hospitals — certainly not enough space for each individual baby to occupy his or her own cot. For example, in some hospitals, there can be up to eight babies in one cot! This can be problematic when trying to prevent the spread of infection but also difficult for mothers who have little to no space to watch over their newborns when they stay at the hospital to breastfeed.

There are several implications of having multiple babies in a single cot that we would like to address. First, the risk of hospital-acquired infections greatly increases because of the close contact of the babies. This close contact also makes it difficult for nurses and caretakers to monitor each baby. In addition, many babies may need to be transported to other hospitals because of a lack of bed space, moving the patients and their caretakers farther from home.

Ghana 4-2
The horizontal sliding mechanism of the Multi-Cot allows each newborn to be safely removed from the structure, regardless of the cot level.

Ghana group 4-3

After learning about this problem, we began thinking of ways to decrease the complications associated with having multiple newborns in one cot. During the brainstorming session, the key element that led to our solution was actually how we view the problem. We started to see the issue as a lack of horizontal space – meaning the inability to add more cots horizontally without physically expanding the newborn ward. If expanding the horizontal space is not possible, then why not try to make better use of the vertical space that is already available? This concept of vertical space led us to the idea of the Multi-Cot, which involves three smaller newborn cots stacked vertically, with space between each cot to provide proper airflow. With clear plastic sides and an open top, each baby would be easily seen from every direction. Finally, to ensure safety when removing newborns from the lower levels, we added a sliding mechanism to our design to allow the lower cots to slide horizontally and eliminate any vertical obstructions when picking up the baby.

As we anticipate developing the Multi-Cot, we must consider multiple factors. Our main consideration is safety, which includes the Multi-Cot’s stability, the visibility of every child, and the ability to be sanitized. Other factors to be considered include the cost, as well as the ease of physical construction and dismantling; however, we would address these details later in the design process.