Hexbyte Glen Cove Potential new gene editing tools uncovered

Hexbyte Glen Cove

Credit: CC0 Public Domain

Few developments have rocked the biotechnology world or generated as much buzz as the discovery of CRISPR-Cas systems, a breakthrough in gene editing recognized in 2020 with a Nobel Prize. But these systems that naturally occur in bacteria are limited because they can make only small tweaks to genes. In recent years, scientists discovered a different system in bacteria that might lead to even more powerful methods for gene editing, given its unique ability to insert genes or whole sections of DNA in a genome.

New research from The University of Texas at Austin dramatically expands the number of naturally occurring versions of this system, giving researchers a wealth of potential new tools for large-scale gene editing.

Other scientists had identified clusters of genes that use CRISPR to insert themselves into different places in an organism’s genome, dubbed CRISPR-associated transposons (CASTs). Earlier work has shown they can be used to add an entire gene or large DNA sequence to the genome, at least for bacteria.

Now a team led by Ilya Finkelstein and Claus Wilke at UT Austin have expanded the number of likely CASTs from about a dozen to nearly 1,500. They published their results this week in the journal Proceedings of the National Academy of Sciences.

“With CASTs, we could potentially insert lots of genes, called ‘gene cassettes,’ encoding multiple complicated functions,” said Finkelstein, associate professor of molecular biosciences, who conceived and headed the research. Among other things, this opens up the possibility of treating complex diseases associated with more than one gene.

CRISPR researcher and Nobel laureate Jennifer Doudna has predicted CASTs will be a critical element in expanding genetic engineers’ toolkit, making it possible to introduce “any change, at any genetic location, in any organism” within the decade, according to Genetic Engineering and Biotechnology News.

Using the Stampede2 supercomputer at the Texas Advanced Computing Center (TACC), the team combed through the world’s largest database of genome fragments from microbes that have not yet been cultured in the lab or fully sequenced.

“Without the resources of TACC, this would have been impossible,” said Wilke, professor and chair of the Department of Integrative Biology, who led the data-engineering part of the project.

He estimates that if the search was run on a powerful desktop computer, it would have taken years. Instead, with one of the university’s supercomputers, the final analysis was completed within a few weeks. Three graduate students—James Rybarski, Kuang Hu and Alexis Hill—worked full time on various aspects of the project for nearly two years.

“The term for this is bioprospecting,” Finkelstein said. “It was like sifting through a lot of silt and junk to find the occasional gold nugget.”

The UT Austin team found 1,476 new putative CASTs, including three new families, doubling the number of known families. They have already exerpimentally verified several of these and plan to continue testing more. Ultimately, Finkelstein predicts most will turn out to be true CASTs.

“If you have just a handful [of CASTs], it’s unlikely that you have the best ones in existence,” Wilke said. “By having more than a thousand, we can start to find out which ones are easiest to work with or most efficient or accurate. Hopefully there are new gene-editing systems that can do things better than the systems we had beforehand.”

In the short term, Finkelstein said many of these new systems should be adaptable to genetically engineering bacteria. The long-term challenge, Finkelstein said, is to “domesticate” the systems to work in our cells.

“The holy grail is to get this working in mammalian cells,” Finkelstein said.

More information:
James R. Rybarski et al, Metagenomic discovery of CRISPR-associated transposons, Proceedings of the National Academy of Sciences (2021). DOI: 10.1073/pnas.2112279118

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Hexbyte Glen Cove Potential plumes on Europa could come from water in the crust thumbnail

Hexbyte Glen Cove Potential plumes on Europa could come from water in the crust

Hexbyte Glen Cove

This illustration of Jupiter’s icy moon Europa depicts a cryovolcanic eruption in which brine from within the icy shell could blast into space. A new model proposing this process may also shed light on plumes on other icy bodies. Credit: Justice Wainwright

Plumes of water vapor that may be venting into space from Jupiter’s moon Europa could come from within the icy crust itself, according to new research. A model outlines a process for brine, or salt-enriched water, moving around within the moon’s shell and eventually forming pockets of water—even more concentrated with salt—that could erupt.

Europa scientists have considered the possible plumes on Europa a promising way to investigate the habitability of Jupiter’s icy moon, especially since they offer the opportunity to be directly sampled by spacecraft flying through them. The insights into the activity and composition of the ice shell covering Europa’s global, interior ocean can help determine if the ocean contains the ingredients needed to support life.

This new work that offers an additional scenario for some plumes proposes that they may originate from pockets of embedded in the icy shell rather than water forced upward from the ocean below. The source of the plumes is important: Water originating from the icy crust is considered less hospitable to life than the global interior ocean because it likely lacks the energy that is a necessary ingredient for life. In Europa’s ocean, that energy could come from hydrothermal vents on the sea floor.

“Understanding where these water plumes are coming from is very important for knowing whether future Europa explorers could have a chance to actually detect life from space without probing Europa’s ocean,” said lead author Gregor Steinbrügge, a postdoctoral researcher at Stanford’s School of Earth, Energy & Environmental Sciences.

Using images collected by NASA’s Galileo spacecraft, the researchers developed a model to propose how a combination of freezing and pressurization could lead to a cryovolcanic eruption, or a burst of frigid water. The results, published Nov. 10 in Geophysical Research Letters, may shed light on eruptions on other icy bodies in the solar system.

The researchers focused their analyses on Manannán, an 18-mile-wide (29-kilometer-wide) crater on Europa that resulted from an impact with another celestial object tens of millions of years ago. Reasoning that such a collision would have generated tremendous heat, they modeled how the melted ice and subsequent freezing of the water pocket within the icy shell could have pressurized it and caused the water to erupt.

“The comet or asteroid hitting the ice shell was basically a big experiment which we’re using to construct hypotheses to test,” said co-author Don Blankenship, senior research scientist at the University of Texas Institute for Geophysics (UTIG) and principal investigator of the radar instrument, REASON (Radar for Europa Assessment and Sounding: Ocean to Near-surface), that will fly aboard NASA’s upcoming Europa Clipper spacecraft. “Our model makes specific predictions we can test using data from the radar and other instruments on Europa Clipper.”

The model indicates that as Europa’s water partially froze into ice following the impact, leftover pockets of water could have been created in the moon’s surface. These salty water pockets can move sideways through Europa’s ice shell by melting adjacent regions of ice and consequently become even saltier in the process.

A Salty Driving Force

The model proposes that when a migrating brine pocket reached the center of Manannán Crater, it became stuck and began freezing, generating pressure that eventually resulted in a plume, estimated to have been over a mile high (1.6 kilometers). The eruption of this plume left a distinguishing mark: a spider-shaped feature on Europa’s surface that was observed by Galileo imaging and incorporated into the researchers’ model.

“Even though plumes generated by brine pocket migration would not provide direct insight into Europa’s ocean, our findings suggest that Europa’s ice shell itself is very dynamic,” said co-lead author Joana Voigt, a graduate research assistant at the University of Arizona, in Tucson.

The relatively small size of the that would form at Manannán indicates that impact craters probably can’t explain the source of other, larger plumes on Europa that have been hypothesized based on data from Galileo and NASA’s Hubble Space Telescope, researchers said. But the process modeled for the Manannán eruption could happen on other icy bodies—even without an impact event.

“The work is exciting, because it supports the growing body of research showing there could be multiple kinds of plumes on Europa,” said Robert Pappalardo of NASA’s Jet Propulsion Laboratory in Southern California and project scientist of the Europa Clipper mission. “Understanding plumes and their possible sources strongly contributes to Europa Clipper’s goal to investigate Europa’s habitability.”

Missions such as Europa Clipper help contribute to the field of astrobiology, the interdisciplinary research on the variables and conditions of distant worlds that could harbor life as we know it. While Europa Clipper is not a life-detection mission, it will conduct detailed reconnaissance of Europa and investigate whether the icy moon, with its subsurface ocean, has the capability to support life. Understanding Europa’s habitability will help scientists better understand how life developed on Earth and the potential for finding life beyond our planet.

More information:
G. Steinbrügge et al. Brine Migration and Impact‐Induced Cryovolcanism on Europa, Geophysical Research Letters (2020). DOI: 10.1029/2020GL090797