Yale scientists model artificial energy cells

Chemical engineers design an artificial electrocyte that could be a power source for medical implants.

Researchers at Yale University have created a blueprint for artificial cells that are more powerful and efficient than the natural cells they mimic and could one day power tiny medical implants. Their findings were published online in Nature Nanotechnology on September 21.

The scientists began by exploring whether an artificial version of the electrocyte—the energy-generating cells in electric eels—could be designed as a potential power source. “The electric eel is very efficient at generating electricity,” said Jian Xu, Ph.D., a postdoctoral associate in the Department of Chemical Engineering. “It can generate more electricity than a lot of electrical devices.”

Xu came up with the first blueprint that shows how the electrocyte’s different ion channels work together to produce the fish’s electricity while he was a graduate student under David A. LaVan, Ph.D., a former assistant professor of mechanical engineering now at the National Institute of Standards and Technology.

But the scientists didn’t stop there. “We’re still trying to understand how the mechanisms in these cells work,” said LaVan. “But we asked ourselves: ‘Do we know enough to sit down and start thinking about how to build these things?’ Nobody had really done that before.”

Using the new blueprint—based on a mathematical model—as a guide, LaVan and Xu set about designing an artificial cell that could replicate the electrocyte’s energy production. “We wanted to see if nature had already optimized the power output and energy conversion efficiency of this cell,” said Xu. “And we found that an artificial cell could actually outperform a natural cell, which was a very surprising result.”

The artificial cell LaVan and Xu modeled is capable of producing 28 percent more electricity than the eel’s own electrocyte, with 31 percent more efficiency in converting the cell’s chemical energy—derived from the eel’s food—into electricity.

While eels use thousands of electrocytes to produce charges of up to 600 volts, LaVan and Xu have shown that it would be possible to create a smaller “bio-battery” using several dozen artificial cells. The tiny bio-batteries would need to be only about a quarter-inch thick to produce the small voltages used to power such tiny electrical devices as retinal implants or other prostheses.

Although the engineers came up with a design, it will still be some time before the artificial cells can be built—they will still need a power source. LaVan speculates that the cells could be powered in a way similar to their natural counterparts. Bacteria, he suggested, could be employed to recycle ATP—the molecule that transfers energy within cells—using glucose, a common source of chemical energy derived from food.

With an energy source in place, the artificial cells could one day power a medical implant and would provide a big advantage over battery-operated devices. “If it breaks, there are no toxins released into your system,” said Xu. “It would be just like any other cell in your body.”

—Suzanne Taylor Muzzin

A gene that helps blood vessels feed tumor growth also aids in brain plasticity

A gene that typically helps rogue blood vessels feed tumor growth also appears to play a helpful role in the body—in brain development. Slight genetic variations in the vascular endothelial growth factor (VEGF) gene sequence correlate with changes in the size of the hippocampus, the brain structure involved in memory, emotion and learning. These changes may be linked to a slew of neuropsychiatric disorders including major depression, schizophrenia and dementia.

“There may be subsets of individuals, for example with mood disorder or bipolar disorder, who have hippocampal differences, and they may be the ones who carry these variations in VEGF,” explained Hilary Blumberg, M.D., associate professor of psychiatry, director of the Mood Disorders Research Program and lead author of a paper published online in Biological Psychiatry on August 14.

The researchers used magnetic resonance imaging to determine hippocampus volumes in a group of healthy volunteers who had slight differences in the VEGF gene encoded in their DNA. They then employed statistical analysis to identify any correlation between hippocampus differences and VEGF differences. The study findings suggest that variations in VEGF might contribute to individual differences in hippocampus size and structure.

These findings build on pioneering work conducted by one of the paper’s co-authors, Ronald S. Duman, Ph.D., Elizabeth Mears and House Jameson Professor of Psychiatry, professor of pharmacology and director of the Division of Molecular Psychiatry and Abraham Ribicoff Research Facilities. Duman recently explored VEGF function in the brain and found that it helped new nerve cells grow, specifically in the hippocampus.

Playing a part in neurogenesis is an unconventional role for VEGF. The gene is known to help cancers grow by laying down new networks of blood vessels that feed malignant cells. Blocking VEGF function is a main goal in the treatment of breast, lung and colorectal cancers, among others.

Joel E. Gelernter, M.D., professor of psychiatry and director of the Division of Human Genetics in Psychiatry, who was examining genetic variations in VEGF, joined Blumberg and Duman for a collaborative effort.

“We’re trying to understand at a basic level of cell signaling how disruptions or alterations could contribute to the function of the hippocampus and circuits within the hippocampus, and how these disruptions influence behavior and illness,” said Duman. Toward that end, Gelernter offered up his genetic expertise, Duman contributed knowledge about the molecular role of VEGF in the brain from his animal studies and Blumberg brought her brain imaging know-how to bear.

The findings of the current study complement another recent discovery from the research trio. They found that, compared to healthy subjects, adults with bipolar disorder had significantly smaller hippocampus volumes, which were linked to variations in the brain-derived neurotrophic growth factor (BDNF) gene (published online on August 13 in Neuropsychopharmacology). Duman predicts that VEGF may behave similarly, in that VEGF variations may make individuals either more or less vulnerable to stress-related mood disorders.

To follow up on this prediction, Blumberg and co-lead author Fei Wang, M.D., Ph.D., plan to study VEGF genetic variations in individuals with mood disorders to understand how these gene changes may influence both brain structure and behavior. Ultimately, identifying genetic variants that predispose individuals to mood disorders could pave the way to patient screening for early disease detection and possibly smarter treatments.

—Kara A. Nyberg

et cetera

Fix-it kit for faulty genes

School of Medicine researchers led by Peter M. Glazer, M.D. ’87, Ph.D. ’87, HS ’91, department chair and the Robert E. Hunter Professor of Therapeutic Radiology and professor of genetics, have found a new approach to gene therapy, opening up the possibility of new treatments for inherited hematologic diseases.

In the September 9 issue of the Proceedings of the National Academy of Sciences, the researchers report that they developed genetic “repair kits” consisting of chemically altered pieces of DNA, which bind to human genes and trigger the cell’s own repair systems to fix such mutated genes as the one that causes thalassemia, an inherited blood disease. The faulty gene was fixed even in human bone marrow cells, meaning that the genetic repair could be inherited by newly generated blood cells.

The new technique employs small pieces of synthetic DNA that are easy to insert into cells and do not require viruses for delivery.

—John Curtis

Junk DNA and evolution

Humans can handle tools and walk upright thanks to a handful of letters in their genome, Yale scientists said in a report published in Science in September. Evolution, they suggest, may have been driven not only by changes in genes but also by changes in the sequences that control them.

Some sequences, previously thought of as “junk DNA” because they do not code for proteins, regulate genes that direct human development. With colleagues in California, Singapore and the United Kingdom, the Yale team characterized in mouse embryos a human sequence that had changed since humans and chimpanzees diverged. This sequence drove gene expression at the base of the mouse versions of the primordial “thumb” in the forelimb and the “great toe” in the hind limb.

“The long-term goal is to find many sequences like this and use the mouse to model their effects on the evolution of human development,” said James Noonan, Ph.D., assistant professor of genetics and senior author of the study.

—J.C.


			Originally published in Yale Medicine, Winter 2009. Copyright © 2009 Yale University School of Medicine. All rights reserved.