Bacterial immune systems take the stage

The new discoveries are exciting because of the new windows they provide on the evolution of immune systems and the eternal battle between viruses and the organisms they infect.

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April 8, 2018 01:13
3 minute read.
Bacteria (illustrative)

Bacteria (illustrative). (photo credit: REUTERS)

Until a decade ago, scientists were not aware that bacteria had complex immune systems that could keep up with the pace of evolution in viruses called phages that infect bacteria. That changed with the discovery of what is now the most famous bacterial immune mechanism: CRISPR. This is a natural gene editor that has revolutionized the world of biological research in thousands of labs around the world. Researchers now understand that most microorganisms have sophisticated immune systems of which CRISPR is just one element; but there has been no good way to identify these systems.

In a massive, systematic study, Prof. Rotem Sorek and his team at the Weizmann Institute of Science in Rehovot have now revealed the existence of 10 previously unknown immune defense mechanisms in bacteria.

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“The systems we discovered are unlike anything we had seen before,” said Sorek. “But among them, we think there are one or two that might have the potential to increase the gene-editing toolbox and others that point to the origins of the human immune system.” The results of their study were recently published in the journal Science.

Bacteria cannot rely on CRISPR alone in the war against phages, explained Sorek, a member of the institute’s molecular genetics department. Indeed many phages have “anti-CRISPR” proteins that cancel CRISPR activity, suggesting that other systems take up the slack.

Sorek and his team began their search for these systems by creating a computer program to scan all the bacterial genomes that have ever been sequenced – around 50,000 genomes in all.

Rather than look for sequences with predefined characteristics, the algorithms they created searched for the “statistical signatures” of genes involved in defense – for example, their location in “defense islands” where several defense-related genes are found near one another. Then, because immune system genes rarely work alone – even in bacteria – the researchers developed complex computer analytic methods so as to understand which genes join forces and work together to form a defense system.

Once they had narrowed down the possible defense genes from millions to several hundred, the researchers needed to test the candidate mechanisms they had identified. Rather than attempting to isolate the genetic sequences from hundreds of different bacteria, the team turned to synthetic biology: getting the genes made to order. They sent the strings of gene code – totaling something like 400,000 bases, or “letters” of genetic code – to a commercial lab where dozens of different multi-gene systems were synthesized for testing.

These synthetic systems were inserted into lab bacteria whose natural immune systems were inactivated. The bacteria were then exposed to phages and other infective elements to see if the transplanted defense system was a viable one. Out of the various systems the researchers examined, 10 strongly protected the lab bacteria from infection, thus identifying them as new immune defense systems. The researchers still don’t know how the new bacterial immune systems function.

“The fact that we managed to find 10 new bacterial defense systems implies there are even more out there,” concluded Sorek.

“The new discoveries are exciting because of the new windows they provide on the evolution of immune systems and the eternal battle between viruses and the organisms they infect. Any one of the new systems we found might be the next gene-editing tool – or perhaps even the foundation of even more exciting molecular tools.”


LIGHTNING LESS LIKELY IN A WARMING PLANET

Lightning may strike less often in the future across the globe as the planet warms, a scientific study from the Universities of Edinburgh, Leeds and Lancaster suggests. The research, published in Nature Climate Change, forecasts a 15% drop in the average number of lightning flashes worldwide by the turn of this century if global temperatures turn out to be in the top range of forecasts.

A drop in the incidence of lightning strikes could impact on the frequency of wildfires, especially in tropical regions. It could also lower the incidence of lightning strikes to infrastructure and affect how greenhouse gases in the atmosphere contribute to climate change.

The team found a new way to calculate the likely incidence of lightning flashes from storm clouds. Unlike traditional calculations of lightning flashes at the global scale, which are based on the height of clouds, their approach takes into account the movement of tiny ice particles that form and move within clouds. Electrical charges build up in these ice particles, and in cold water droplets and soft hail formed inside clouds. These are discharged during storms, giving rise to lightning flashes and thunder. Scientists estimate there are 1.4 billion lightning flashes each year around the world.


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