Tufts University

Two common viruses could trigger Alzheimer’s disease

/ Katie Sharify / Leave a comment

Researchers from Tufts University and the University of Oxford have found that two common viruses —the varicella zoster and herpes simplex viruses— could trigger Alzheimer’s disease.

Varicella zoster (VZV) is an extremely common virus causes which causes chickenpox. Once cured of the first infection, the virus tends to linger in peripheral nerves where they remain dormant. When these dormant viruses are reactivated, they cause shingles.

HSV-1, the subtype of the herpes simplex virus, causes both oral and genital herpes. It is a very common infection, affecting nearly 4 million people worldwide under the age of 50 years. The American Sexual Health Organization estimates that around one in two adults has oral herpes in the United States. 

Cytokines are produced in response to VZV. Cytokines are part of a healthy immune system. These small proteins help control the growth and activity of your blood cells and immune cells. Cytokines tell your immune system to do its job. But when too many cytokines are released, it can cause your immune system to go into overdrive, resulting in cytokine storm.

In their findings, published in the Journal of Alzheimer’s Disease, researchers found that when VZV infect neurons, they trigger an inflammatory response due to this overproduction of cytokines. This inflammatory response in turn awakens the herpes simplex viruses which typically lie dormant and harmless in the brain. With both viruses now active, inflammation throughout the brain is aggravated, potentially leading to the formation of plaque and the slow deterioration of neurons—both hallmarks of Alzheimer’s.

The study’s leading author, Dana Cairns, along with her team of collaborators gathered data by using lab grown cultures of brain nerve, or neural, stem cells. They found that infecting neurons with varicella zoster alone was not enough to trigger Alzheimer-like properties. However, when the herpes simplex was already lying-in wait, varicella zoster initiated a series of events that resulted in plaques, tangled fibers and brain damage.

“It’s a one-two punch of two viruses that are very common and usually harmless, but the lab studies suggest that if a new exposure to VZV wakes up dormant HSV-1, they could cause trouble,” explains Cairns. One of her collaborators, Oxford’s Ruth Itzhaki, was one of the first scientists to suggest a link between herpes infections and Alzheimer’s.

The California Institute for Regenerative Medicine (CIRM) has already invested almost $35 million in 21 different Alzheimer’s projects. In addition, we are committed to investing at least $1.5 billion in treatments that target conditions affecting the brain and central nervous system (CNS), including Alzheimer’s. 

Meet xenobots 2.0 – the next generation of living robots

/ Yimy Villa / 2 Comments
Xenobots scurry about and can work together in swarms.
Source: Doug Blackiston

Last year we wrote about how researchers at the University of Vermont and Tufts University were able to create what they call xenobots – the world’s first living, self healing robots created from frog stem cells.

Now, the same team has created an upgraded version of these robots that they have dubbed Xenobots 2.0. These upgraded robots have the ability to self-assemble a body from single cells, do not require muscle cells to move, and demonstrate the capability to record memory. In comparison to the previous version developed, Xenobots 2.0 can move faster, navigate different environments, have longer lifespans, and still have the ability to work together in groups and heal themselves if damaged. 

To create Xenobots 2.0, researchers at Tufts University took stem cells from embryos from the African frog Xenopus laevis (which is where the name Xenobots is derived from). The team then allowed the stem cells to self assemble and grow into sphere-like shapes. In a few days, these newly formed stem cell spheroids produced tiny hair-like projections, allowing them to move back and forth or rotate in a specific way.

Meanwhile, scientists at the University of Vermont were running computer simulations that modeled different shapes of the Xenobots to see if they might exhibit different behaviors, both individually and in groups. The team ran hundreds of thousands of random environmental conditions using an evolutionary algorithm and used these simulations to identify the Xenobots most able to work together in swarms to gather large piles of debris in a field of particles. What they found was that Xenobots 2.0 are much faster and better at tasks such as garbage collection. They can also cover large flat surfaces or travel through narrow capillaries.

Using a fluorescent protein, Xenobots 2.0 record exposure to blue light by turning green. Source: Doug Blackiston

Going one step further for Xenobots 2.0, the researchers at Tufts University engineered the Xenobots in a way to enable them to record one bit of information. By introducing a fluorescent protein, they were able to get the Xenobots to glow green normally. However, if the Xenobots were exposed to blue light, they would start to glow red instead.

To test this memory function, the team allowed ten Xenobots to swim around a surface on which one spot is illuminated with a beam of blue light. After two hours, they found that three bots glowed red and the rest remained green, effectively recording their travel experience.

In a press release, robotics expert Josh Bongard from the University of Vermont who played an integral role in this study elaborated on what these findings could implicate.

“When we bring in more capabilities to the bots, we can use the computer simulations to design them with more complex behaviors and the ability to carry out more elaborate tasks. We could potentially design them not only to report conditions in their environment but also to modify and repair conditions in their environment.”

Xenobots 2.0 were also able to heal quite rapidly, closing the majority of a deep cut half their thickness within 5 minutes of the injury. All injured bots were able to ultimately heal the wound, restore their shape, and continue their work as before.

In the same press release, Dr. Michael Levin, professor at Tufts University and corresponding author of the study, had this to say.

“The biological materials we are using have many features we would like to someday implement in the bots – cells can act like sensors, motors for movement, communication and computation networks, and recording devices to store information. One thing the Xenobots and future versions of biological bots can do that their metal and plastic counterparts have difficulty doing is constructing their own body plan as the cells grow and mature, and then repairing and restoring themselves if they become damaged. Healing is a natural feature of living organisms, and it is preserved in Xenobot biology.”

The full results of this study were published in Science Robotics.

You can learn more about this research from Dr. Michael Levin by watching his TED Talk linked below:

I Sing the Bioelectric: Long-Distance Electrical Signals Guide Cell Growth and Repair

/ cirmweb / Leave a comment

Genes turn on, and genes turn off. Again and again, the genes that together comprise the human genome receive electrical signals that can direct when they should be active—and when they should be dormant. This intricate pattern of signals is a part of what guides an embryonic stem cell to grow and mature into any one of the many types of cells that make up the human body.

Bioelectric signals sent between cells—even cells at great distance from each other—have been found to carry important instructions relating to the growth, development and repair of organs such as the brain.

Bioelectric signals sent between cells—even cells at great distance from each other—have been found to carry important instructions relating to the growth, development and repair of organs such as the brain.

These electrical signals that guide cell growth have long been described as molecular ‘switches.’ But now, scientists at Tufts University have decoded these electrical signals—and discovered that they are far more complex than we had ever imagined.

Reporting in today’s issue of the Journal of Neuroscience, lead author Michael Levin and his Tufts research team have mapped the electrical signals transmitted between cells during development, and found that not only do these signals direct when a gene should be switched on, they also carry their own set of instructions, crucial to cellular development. Using the example of brain formation, Levin explained in today’s news release:

“We’ve found that cells communicate, even across long distances in the embryo, using bioelectrical signals, and they use this information to know where to form a brain and how big that brain should be. The signals are not just necessary for normal development; they are instructive.”

Instead of a molecular switchboard, an analogy that some have used to describe these bioelectrical signals, Levin likened the system to a computer. The signals themselves act like software programs, delivering instructions and information between cells at precisely the right time—even cells at great distance from one another.

Using tadpole embryos as a model, the team identified that the pattern of changes in voltage levels between cell membranes, called cellular resting potential, is the source of these bioelectrical signals, which are crucial to cellular development.

Specifically, the team mapped the changing voltage levels in embryonic stem cells in regards to the formation of the brain. In addition to discovering that these bioelectric signals instruct the formation of organs such as the brain, their discovery also hints at how scientists could manipulate these signals to repair tissues or organs that have been damaged—or even to grow new, healthy tissues.

“This latest research also demonstrated molecular techniques for ‘hijacking’ this bioelectric communication to force the body to make new brain tissue at other locations and to fix genetic defects that cause brain malformation,” Levin explained. “This means we may be able to induce growth of new brain tissue to address birth defects or injury, which is very exciting for regenerative medicine.”

In addition, the authors argue that modifying the bioelectrical signals to generate tissue—rather than modifying the genes themselves—may reduce the risk of adverse effects that may crop up by modifying genes directly.

While it’s early days for this work, Levin and his team foresee ways to apply this knowledge directly to medicine, for example by developing electricity-modulating drugs—which they call ‘electroceuticals’—that can repair damaged or defective tissue, and induce tissue growth.