Xiaoyu Yang, a graduate student at Rice, is the lead author on a study published in the journal Science on smart cell design. Photo by Jeff Fitlow/ Courtesy Rice University

Bioengineers at Rice University have developed a “new construction kit” for building custom sense-and-respond circuits in human cells, representing a major breakthrough in the field of synthetic biology, which could "revolutionize" autoimmune disease and cancer therapeutics.

In a study published in the journal Science, the team focused on phosphorylation, a cellular process in the body in which a phosphate group is added to a protein, signaling a response. In multicellular organisms, phosphorylation-based signaling can involve a multistage, or a cascading-like effect. Rice’s team set out to show that each cycle in a cascade can be treated as an elementary unit, meaning that they can be reassembled in new configurations to form entirely novel pathways linking cellular inputs and outputs.

Previous research on using phosphorylation-based signaling for therapeutic purposes has focused on re-engineering pathways.

“This opens up the signaling circuit design space dramatically,” Caleb Bashor, assistant professor of bioengineering and biosciences and corresponding author on the study, said in a news release. “It turns out, phosphorylation cycles are not just interconnected but interconnectable … Our design strategy enabled us to engineer synthetic phosphorylation circuits that are not only highly tunable but that can also function in parallel with cells’ own processes without impacting their viability or growth rate.”

Bashor is the deputy director for the Rice Synthetic Biology Institute, which launched last year.

The Rice lab's sense-and-respond cellular circuit design is also innovative because phosphorylation occurs rapidly. Thus, the new circuits could potentially be programmed to respond to physiological events in minutes, compared to other methods, which take hours to activate.

Rice’s team successfully tested the circuits for sensitivity and their ability to respond to external signals, such as inflammatory issues. The researchers then used the framework to engineer a cellular circuit that can detect certain factors, control autoimmune flare-ups and reduce immunotherapy-associated toxicity.

“This work brings us a whole lot closer to being able to build ‘smart cells’ that can detect signs of disease and immediately release customizable treatments in response,” Xiaoyu Yang, a graduate student in the Systems, Synthetic and Physical Biology Ph.D. program at Rice who is the lead author on the study, said in a news release.

Ajo-Franklin, a professor of biosciences, bioengineering, chemical and biomolecular engineering and a Cancer Prevention and Research Institute of Texas Scholar, added “the Bashor lab’s work vaults us forward to a new frontier — controlling mammalian cells’ immediate response to change.”

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Rice University lands $18M to revolutionize lymphatic disease detection

fresh funding

An arm of the U.S. Department of Health and Human Services has awarded $18 million to scientists at Rice University for research that has the potential to revolutionize how lymphatic diseases are detected and help increase survivability.

The lymphatic system is the network of vessels all over the body that help eliminate waste, absorb fat and maintain fluid balance. Diseases in this system are often difficult to detect early due to the small size of the vessels and the invasiveness of biopsy testing. Though survival rates of lymph disease have skyrocketed in the United States over the last five years, it still claims around 200,000 people in the country annually.

Early detection of complex lymphatic anomalies (CLAs) and lymphedema is essential in increasing successful treatment rates. That’s where Rice University’s SynthX Center, directed by Han Xiao and Lei Li, an assistant professor of electrical and computer engineering, comes in.

Aided by researchers from Texas Children’s Hospital, Baylor College of Medicine, the University of Texas at Dallas and the University of Texas Southwestern Medical Center, the center is pioneering two technologies: the Visual Imaging System for Tracing and Analyzing Lymphatics with Photoacoustics (VISTA-LYMPH) and Digital Plasmonic Nanobubble Detection for Protein (DIAMOND-P).

Simply put, VISTA-LYMPH uses photoacoustic tomography (PAT), a combination of light and sound, to more accurately map the tiny vessels of the lymphatic system. The process is more effective than diagnostic tools that use only light or sound, independent of one another. The research award is through the Advanced Research Projects Agency for Health (ARPA-H) Lymphatic Imaging, Genomics and pHenotyping Technologies (LIGHT) program, part of the U.S. HHS, which saw the potential of VISTA-LYMPH in animal tests that produced finely detailed diagnostic maps.

“Thanks to ARPA-H’s award, we will build the most advanced PAT system to image the body’s lymphatic network with unprecedented resolution and speed, enabling earlier and more accurate diagnosis,” Li said in a news release.

Meanwhile, DIAMOND-P could replace the older, less exact immunoassay. It uses laser-heated vapors of plasmonic nanoparticles to detect viruses without having to separate or amplify, and at room temperature, greatly simplifying the process. This is an important part of greater diagnosis because even with VISTA-LYMPH’s greater imaging accuracy, many lymphatic diseases still do not appear. Detecting biological markers is still necessary.

According to Rice, the efforts will help address lymphatic disorders, including Gorham-Stout disease, kaposiform lymphangiomatosis and generalized lymphatic anomaly. They also could help manage conditions associated with lymphatic dysfunction, including cancer metastasis, cardiovascular disease and neurodegeneration.

“By validating VISTA-LYMPH and DIAMOND-P in both preclinical and clinical settings, the team aims to establish a comprehensive diagnostic pipeline for lymphatic diseases and potentially beyond,” Xiao added in the release.

The ARPA-H award funds the project for up to five years.

Houston doctor wins NIH grant to test virtual reality for ICU delirium

Virtual healing

Think of it like a reverse version of The Matrix. A person wakes up in a hospital bed and gets plugged into a virtual reality game world in order to heal.

While it may sound far-fetched, Dr. Hina Faisal, a Houston Methodist critical care specialist in the Department of Surgery, was recently awarded a $242,000 grant from the National Institute of Health to test the effects of VR games on patients coming out of major surgery in the intensive care unit (ICU).

The five-year study will focus on older patients using mental stimulation techniques to reduce incidences of delirium. The award comes courtesy of the National Institute on Aging K76 Paul B. Beeson Emerging Leaders Career Development Award in Aging.

“As the population of older adults continues to grow, the need for effective, scalable interventions to prevent postoperative complications like delirium is more important than ever,” Faisal said in a news release.

ICU delirium is a serious condition that can lead to major complications and even death. Roughly 87 percent of patients who undergo major surgery involving intubation will experience some form of delirium coming out of anesthesia. Causes can range from infection to drug reactions. While many cases are mild, prolonged ICU delirium may prevent a patient from following medical advice or even cause them to hurt themselves.

Using VR games to treat delirium is a rapidly emerging and exciting branch of medicine. Studies show that VR games can help promote mental activity, memory and cognitive function. However, the full benefits are currently unknown as studies have been hampered by small patient populations.

Faisal believes that half of all ICU delirium cases are preventable through VR treatment. Currently, a general lack of knowledge and resources has been holding back the advancement of the treatment.

Hopefully, the work of Faisal in one of the busiest medical cities in the world can alleviate that problem as she spends the next half-decade plugging patients into games to aid in their healing.