Adding Letters to the DNA Alphabet

semi-synthetic bacterium

Credit: William B. Kiosses

The recipes for life, going back billions of years to the earliest single-celled organisms, are encoded in a DNA alphabet of just four letters. But is four as high as the DNA code can go? Or, as researchers have long wondered, is it chemically and biologically possible to expand the DNA code by a couple of letters?

A team of NIH-funded researchers is now answering these provocative questions. The researchers recently engineered a semi-synthetic bacterium containing DNA with six letters, including two extra nucleotides [1, 2]. Now, in a report published in Nature, they’ve taken the next critical step [3]. They show that bacteria, like those in the photo, are not only capable of reliably passing on to the next generation a DNA code of six letters, they can use that expanded genetic information to produce novel proteins unlike any found in nature.

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Can Artificial Cells Take Over for Lost Insulin-Secreting Cells?

artificial beta cells

Caption: Artificial beta cell, made of a lipid bubble (purple) carrying smaller, insulin-filled vesicles (green). Imaged with cryo-scanning electron microscope (cryo-SEM) and colorized.
Credit: Zhen Gu Lab

People with diabetes have benefited tremendously from advances in monitoring and controlling blood sugar, but they’re still waiting and hoping for a cure. Some of the most exciting possibilities aim to replace the function of the insulin-secreting pancreatic beta cells that is deficient in diabetes. The latest strategy of this kind is called AβCs, short for artificial beta cells.

As you see in the cryo-SEM image above, AβCs are specially designed lipid bubbles, each of which contains hundreds of smaller, ball-like vesicles filled with insulin. The AβCs are engineered to “sense” a rise in blood glucose, triggering biochemical changes in the vesicle and the automatic release of some of its insulin load until blood glucose levels return to normal.

In recent studies of mice with type 1 diabetes, researchers partially supported by NIH found that a single injection of AβCs under the skin could control blood glucose levels for up to five days. With additional optimization and testing, the hope is that people with diabetes may someday be able to receive AβCs through patches that painlessly stick on their skin.

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Creative Minds: Giving Bacteria Needles to Fight Intestinal Disease

Cammie Lesser

Cammie Lesser

For Salmonella and many other disease-causing bacteria that find their way into our bodies, infection begins with a poke. That’s because these bad bugs are equipped with a needle-like protein filament that punctures the outer membrane of human cells and then, like a syringe, injects dozens of toxic proteins that help them replicate.

Cammie Lesser at Massachusetts General Hospital and Harvard Medical School, Cambridge, and her colleagues are now on a mission to bioengineer strains of bacteria that don’t cause disease to make these same syringes, called type III secretion systems. The goal is to use such “good” bacteria to deliver therapeutic molecules, rather than toxins, to human cells. Their first target is the gastrointestinal tract, where they hope to knock out hard-to-beat bacterial infections or to relieve the chronic inflammation that comes with inflammatory bowel disease (IBD).

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Robotic Exoskeleton Could Be Right Step Forward for Kids with Cerebral Palsy

More than 17 million people around the world are living with cerebral palsy, a movement disorder that occurs when motor areas of a child’s brain do not develop correctly or are damaged early in life. Many of those affected were born extremely prematurely and suffered brain hemorrhages shortly after birth. One of the condition’s most common symptoms is crouch gait, which is an excessive bending of the knees that can make it difficult or even impossible to walk. Now, a new robotic device developed by an NIH research team has the potential to help kids with cerebral palsy walk better.

What’s really cool about the robotic brace, or exoskeleton, which you see demonstrated above, is that it’s equipped with computerized sensors and motors that can detect exactly where a child is in the walking cycle—delivering bursts of support to the knees at just the right time. In fact, in a small study of seven young people with crouch gait, the device enabled six to stand and walk taller in their very first practice session!

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Snapshots of Life: Biological Bubble Machine

plasma membrane vesicles

Credit: Chi Zhao, David Busch, Connor Vershel, Jeanne Stachowiak, University of Texas at Austin

As kids, most of us got a bang out of blowing soap bubbles and watching them float around. Biologists have learned that some of our cells do that too. On the right, you can see two cells (greenish yellow) in the process of forming bubbles, or plasma membrane vesicles (PMVs). During this blebbing process, a cell’s membrane temporarily disassociates from its underlying cytoskeleton, forming a tiny pouch that, over the course of about 30 minutes, is “inflated” with a mix of proteins and lipids from inside the cell. After the PMVs are fully filled, these bubble-like structures are pinched off and released, like those that you see in the background. Certain cells constantly release PMVs, along with other types of vesicles, and may use those to communicate with other cells throughout the body.

This particular image, an entrant in the Biophysical Society’s 2017 Art of Science Image Contest, was produced by researchers working in the NIH-supported lab of Jeanne Stachowiak at the University of Texas at Austin. Stachowiak’s group is among the first to explore the potential of PMVs as specialized drug-delivery systems to target cancer and other disorders [1].

Until recently, most efforts to exploit vesicles for therapeutic uses have employed synthetic versions of a different type of vesicle, called an exosome. But Stachowiak and others have realized that PMVs come with certain built-in advantages. A major one is that a patient’s own cells could in theory serve as the production facility.

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