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Blast Off! Sending Human Tissue Chips into Space

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Tissue Chips in Space

Credit: Josh Valcarcel, NASA

A big challenge in unlocking the mysteries of aging is how long you need to study humans, or even human cells, to get answers. But, in partnership with NASA, NIH is hoping that space will help facilitate this important area of research.

It’s already known, from what’s been seen in astronauts, that the weightless conditions found in space can speed various processes associated with aging. So, might it be possible to use the space station as a lab to conduct aging experiments?

Tracking Peptides in Cell Soup

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Lipid Morphology

Credit: William Wimley, Tulane University, New Orleans

If you think this soup looks unappealing for this year’s Thanksgiving feast, you’re right! If you were crazy enough to take a sip, you’d find it to be virtually flavorless—just a salty base (red) with greasy lipid globules (green) floating on top. But what this colorful concoction lacks in taste, it makes up for as a valuable screening tool for peptides, miniature versions of proteins that our bodies use to control many cellular processes.

In this image, William Wimley, an NIH-supported researcher at Tulane University, New Orleans, has stirred up the soup and will soon add some peptides. These peptides aren’t made by our cells, though. They’re synthesized in the lab, allowing Wimley and team to tweak their chemical structures and hopefully create ones with therapeutic potential, particularly as smart-delivery systems to target cells with greater precision and deliver biological cargoes such as drugs [1].

MicroED: From Powder to Structure in a Half-Hour

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MicroED determines structure in 30 min

Credit: Adapted from Jones et al.

Over the past few years, there’s been a great deal of excitement about the power of cryo-electron microscopy (cryo-EM) for mapping the structures of large biological molecules like proteins and nucleic acids. Now comes word of another absolutely incredible use of cryo-EM: determining with great ease and exquisite precision the structure of the smaller organic chemical compounds, or “small molecules,” that play such key roles in biological exploration and drug development.

The new advance involves a cryo-EM technique called microcrystal-electron diffraction (MicroED). As detailed in a preprint on [1] and the journal Angewandte Chemie [2], MicroED has enabled researchers to take the powdered form of commercially available small molecules and generate high-resolution data on their chemical structures in less than a half-hour—dramatically faster than with traditional methods!

A Ray of Molecular Beauty from Cryo-EM

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Credit: Subramaniam Lab, National Cancer Institute, NIH

Walk into a dark room, and it takes a minute to make out the objects, from the wallet on the table to the sleeping dog on the floor. But after a few seconds, our eyes are able to adjust and see in the near-dark, thanks to a protein called rhodopsin found at the surface of certain specialized cells in the retina, the thin, vision-initiating tissue that lines the back of the eye.

This illustration shows light-activating rhodopsin (orange). The light photons cause the activated form of rhodopsin to bind to its protein partner, transducin, made up of three subunits (green, yellow, and purple). The binding amplifies the visual signal, which then streams onward through the optic nerve for further processing in the brain—and the ability to avoid tripping over the dog.

Tagging Essential Malaria Genes to Advance Drug Development

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Red blood cell infected with malaria-causing parasites

Caption: Colorized scanning electron micrograph of a blood cell infected with malaria parasites (blue with dots) surrounded by uninfected cells (red).
Credit: National Institute of Allergy and Infectious Diseases, NIH

As a volunteer physician in a small hospital in Nigeria 30 years ago, I was bitten by lots of mosquitoes and soon came down with headache, chills, fever, and muscle aches. It was malaria. Fortunately, the drug available to me then was effective, but I was pretty sick for a few days. Since that time, malarial drug resistance has become steadily more widespread. In fact, the treatment that cured me would be of little use today. Combination drug therapies including artemisinin have been introduced to take the place of the older drugs [1], but experts are concerned the mosquito-borne parasites that cause malaria are showing signs of drug resistance again.

So, researchers have been searching the genome of Plasmodium falciparum, the most-lethal species of the malaria parasite, for potentially better targets for drug or vaccine development. You wouldn’t think such work would be too tough because the genome of P. falciparum was sequenced more than 15 years ago [2]. Yet it’s proven to be a major challenge because the genetic blueprint of this protozoan parasite has an unusual bias towards two nucleotides (adenine and thymine), which makes it difficult to use standard research tools to study the functions of its genes.

Now, using a creative new spin on an old technique, an NIH-funded research team has solved this difficult problem and, for the first time, completely characterized the genes in the P. falciparum genome [3]. Their work identified 2,680 genes essential to P. falciparum’s growth and survival in red blood cells, where it does the most damage in humans. This gene list will serve as an important guide in the years ahead as researchers seek to identify the equivalent of a malarial Achilles heel, and use that to develop new and better ways to fight this deadly tropical disease.

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