ASU engineers envision 'guiding' body's cells to help improve health

Controlling the fates of engineered cells opens possibilities for fighting diseases, disabilities

May 17, 2017

Much of what happens inside the human body at its most basic biological level is determined by how its cells transition from one state to another.

In particular, stem cells — the primal cells common to all multicellular organisms— have the ability to divide and differentiate into a range of specialized kinds of cells that are essential to critical bodily systems and functions. Some cells can even change to different kinds of cells more than once. The technology used in Xiao Wang’s Systems and Synthetic Biology Lab can capture images of cellular fluorescence in microfluidic devices. The images are used to illustrate in real time how engineered E. coli cells transition from one state or function to another. Photo by Jessica Hochreiter/ASU Download Full Image

What is still unknown to a significant degree are all the factors within the body’s genetic environment that determine what kinds of specialized cells that the unspecialized stem cells will transition into.

A thorough understanding of what controls the cell differentiation process would unlock secrets to “guiding” cell fates, and open up the potential for developing more and better cell-based medical therapies, according to Xiao Wang.

Wang is an associate professor of biomedical engineering in Arizona State University’s Ira A. Fulton Schools of Engineering and directs the Systems and Synthetic Biology Lab.

HIs lab team and faculty collaborators have been trying to fill in missing pieces of the picture presented by “Waddington’s epigenetic landscape,” a visualization of pathways a cell might follow toward differentiation.

Scientist Conrad Hal Waddington’s illustration of a biological landscape of ridges and valleys that a cell could move along on its way to differentiation was a valuable step forward in genetics in the mid-20th century.

With the benefit of modern advances in mathematical modeling, computer science, bioengineering, physics and molecular biology, Wang and his colleagues have expanded on Waddington’s conceptualization of the determinants of cell fates.

Their conclusions have recently been published in the biomedical and life sciences research journal eLife, in the article “Engineering of a synthetic quadrastable gene network to approach Waddington landscape and cell fate determination.”

man working in lab
Biomedical engineering doctoral student Fuqing Wu conducted the experiments to test Wang’s theories about the mechanisms of cell differentiation. Photo by Jessica Hochreiter/ASU

Biomedical engineering doctoral student Fuqing Wu performed the experiments for the research project and postdoctoral research associate Ri-Qi Su developed the mathematical modeling.

Wang’s chief partner on the project was Ying-Cheng Lai, a Fulton Schools professor of electrical, computer and energy engineering.

The eLife journal editors write that the team has successfully charted how the environment in which cell fates are altered will change in the presence of various chemicals, and that cells’ transitions can be guided by introducing certain chemicals into that landscape in specifically ordered sequences.

“Their work helps us understand how multiple cell fates may be achieved and how we might manipulate cell fate transitions,” the editors write.

The research not only lays a theoretical foundation for how cell differentiation could be controlled, Wang explained, but also provides results of experimentation to support the theory.

The upshot is that by changing the order in which mixtures of particular chemicals and protein molecules are introduced into the environment, one kind of cell can be manipulated into turning into other specific kinds of cells.

With the ability to do that, he envisions being able to someday control the mechanisms that determine cell fates for the purposes of treating infections and diseases, and repairing body tissues and organs.

portrait of professor
Associate Professor Xiao Wang says the most dramatic impact of learning to manipulate the cell transition process might be reducing the need for organ transplants. Photo by Jessica Hochreiter/ASU

He sees potential uses for improving therapies and treatments for Alzheimer’s disease, spinal injuries and even blindness.

The most dramatic impact could be on reducing the need for transplants.

“When tissues or organs are badly damaged, the only option we often have today are transplants. We have to take parts from other bodies,” he said. “But by turning our own cells into the kinds of cells needed to produce specific types of tissues, we might be able to generate that new tissue from our own genetic material.”

Getting to that point will take much more research and experimentation, Wang says, and he plans for his lab to pursue answers to more complex questions about activating cell differentiation and how to best take of advantage of controlling the process.

“We don’t want to over-claim about what might be achieved,” Wang said. “But what we are learning, and the possibilities it raises, is very exciting.”

Joe Kullman

Science writer, Ira A. Fulton Schools of Engineering


Measuring the human impact of weather

World Meteorological Organization issues new records of weather impacts in terms of lives lost

May 18, 2017

The World Meteorological Organization (WMO) has announced today world records for the highest reported historical death tolls from tropical cyclones, tornadoes, lightning and hailstorms. It marks the first time the official WMO Archive of Weather and Climate Extremes has broadened its scope from strictly temperature and weather records to address the impacts of specific events.

“In today’s world, it seems like the latest weather disaster is the worst,” said Randy Cerveny, an Arizona State University professor of geographical sciences and urban planning and chief Rapporteur of Climate and Weather Extremes for WMO. Cerveny is the keeper of the world’s weather extremes. ASU Professor Randy Cerveny, the keeper of the world's weather extremes, says that measuring the impacts of specific weather events "provides a very useful set of baseline numbers against which future disasters can be compared." Download Full Image

“Knowing exactly how bad various types of weather have been in the past has been an integral part of preparing for the future,” Cerveny said. “For example, I have often heard since 2005 that Hurricane Katrina was the deadliest tropical cyclone/hurricane to have ever occurred. While Katrina was bad (more than 2,000 died), it pales in comparison to the tropical cyclone that hit the area of present-day Bangladesh in 1970, that killed an estimated 300,000 people.

“This type of extreme (mortality totals) provides a very useful set of baseline numbers against which future disasters can be compared.” 

“Extreme weather causes serious destruction and major loss of life,” said WMO Secretary-General Petteri Taalas. “That is one of the reasons behind the WMO’s efforts to improve early warnings of multiple hazards and impact-based forecasting, and to learn lessons gleaned from historical disasters to prevent future ones. The human aspect inherent in extreme events should never be lost.”

Cerveny convened an international WMO committee of 19 experts that conducted an in-depth investigation of documented mortality records for five specific weather-related events. The committee’s findings are:

• Highest mortality associated with a tropical cyclone: An estimated 300,000 people killed directly as result of the passage of a tropical cyclone through Bangladesh (at time of incident, East Pakistan) on Nov. 12-13, 1970.

• Highest mortality associated with a tornado: An estimated 1,300 people killed by the April 26, 1989, tornado that destroyed the Manikganj district, Bangladesh.

• Highest mortality (indirect strike) associated with lightning: 469 people killed in a lightning-caused oil tank fire in Dronka, Egypt, on Nov. 2, 1994.

• Highest mortality directly associated with a single lightning flash: 21 people killed by a single stroke of lightning in a hut in Manyika Tribal Trust Lands in Zimbabwe (at the time of incident, Rhodesia) on Dec. 23, 1975.

• Highest mortality associated with a hailstorm: 246 people were killed near Moradabad, India, on April 30, 1888, with hailstones as large as “goose eggs and oranges and cricket balls.”

“These events highlight the deadly tragedies associated with different types of weather,” Cerveny said. “Detailed knowledge of these historical extremes confirm our continuing responsibilities to not only forecast and monitor weather and climate but to utilize that information to save lives around the world so disasters of these types are lessened or even eliminated in the future.”

Cerveny said more event impacts could be added in the future for such weather-related events as floods and heat waves. 

“I think that many people are unaware of exactly how dangerous certain types of weather can be,” Cerveny said. “The more that we are aware of the dangers, hopefully the less likely we will see repeats of these types of disasters.” 

A full list of weather and climate extremes is available at the WMO Archive of Weather and Climate Extremes. 

Associate Director, Media Relations & Strategic Communications