Researchers have figured out a way to make it safer to use and experiment with E. coli bacteria. They have altered these germs so that they are not affected by existing viruses and they can’t escape or spread outside of their controlled environment. This is great news for medicine and industry!
A new study published in the journal Nature on March 15 wants to keep bacterial-produced drugs such as insulin and biofuels clean from viruses. Corrupting viruses can ruin these products, which is really costly. The experiment uses a method known as codon deletion to make sure that bacteria stay safe. To see how it works, you can watch this video produced by the Church lab in 2016.
Scientists working in a lab have announced that they have invented something that could make any kind of virus unable to infect. Akos Nyerges, who works for the Blavatnik Institute at Harvard Medical School and the Wyss Institute, is the one who made this discovery.
Scientists discovered something that makes it difficult for viruses to attack it. Plus, they even made sure no modified parts can go into normal cells. So far all the tests and computer simulations show that this discovery is really secure from viruses.
The scientists created a new way of making any living thing free from viruses and to stop the transfer of genes into or out of something called GMOs (Genetically Modified Organisms). These strategies are becoming more important as researchers explore using GMOs for growing food, stopping diseases, creating fuels or getting rid of pollution in nature.
Scientists are trying to make a special type of bacteria that won’t get sick and won’t carry viruses.
In 2022, some people from Cambridge University believed they had made a type of bacteria called E. coli unable to get sick from viruses. But researchers at Harvard Medical School then joined forces with them and went around to collect samples from places like chicken coops, rat nests and even sewers by the Thames River near their campus. They found that there were still viruses that could infect the modified bacteria despite previous beliefs.
Nyerges was disappointed to find out that the bacteria weren’t completely virus-proof after all.
Their plan involved changing the E. coli bacteria so that it could only use 61 different pieces of genetic code (called codons) instead of their usual 64. It was hoped that this would make it harder for viruses to take control, since they wouldn’t have the missing codes needed for replication.
The HMS team were not satisfied by just deleting codons, as some viruses were still finding ways to work without them. So, Nyerges and his colleagues discovered a new approach: changing the code given by each codon so that organisms can’t make what they used to – something nobody had done with living cells before.
Scientists Trick Viruses with Clever Trickster Molecules
Transfer RNAs (tRNAs) have an important job – they help attach the correct amino acids to the proteins that are being made. For example, when a tRNA recognizes the code TCG, it attaches the amino acid serine.
The Cambridge team deleted codes TCG and TCA (which also requires serine), as well as their matching tRNAs.
The HMS team have now replaced some of the molecules with new trickster ones. Whenever these ‘tricksters’ recognise that they’ve seen TCG or TCA, they add leucine instead of serine. Leucine is incredibly different to serine physically and chemically, according to Nyerges. This means when an invading virus comes along and tries to force the E. coli bacteria to make its own proteins, those clever tricksters mess up the instructions!
If the wrong type of amino acids get added, then proteins in the virus will not form correctly. This means that the virus cannot make more copies of it to use in infecting other cells.
Most viruses have their own special tRNAs which can successfully turn “TCG” and “TCA” into serine. However, some researchers inserted a new, better version of tRNA which actually works so well that it defeats even the original tRNA used by the virus itself.
Nyerges said that it was a tough but worthwhile accomplishment to prove it is possible to change an organism’s genetic material, and only works if they use this special technique. The research might have solved the last major issue that stops bacteria from being completely safe from viruses. But, there still may be something out there that could break the protection.
The team feels better because they know that a virus must change its many parts all together to stop the swapped codons.
“It’s extremely improbable for it to happen naturally,” said Nyerges.
Scientists Unearth New Methods to Protect Against Bacteria and Viruses
This work covers two things to protect us.
The first one guards against a situation where pieces of the genetic code and its properties, like antibiotic strength, can be passed from one living thing to another. This situation occurs all the time.
The scientists changed all of the parts in the modified E. coli cells that usually form leucine and replaced them with two other kinds of building blocks (TCG or TCA). The bacteria were still able to build leucine using certain cheat molecules called tRNAs.
If another organism copies certain modified pieces of its genetic code, the tRNAs within that organism are more likely to interpret it as serine even if it is not. That’s because the translation would result in junk proteins which doesn’t benefit the organism in any way.
According to Nyerges, these mutations will just leave us with a bunch of meaningless information.
Scientists showed that if one of the bacteria’s ‘trickster’ molecules is transferred to another organism, it will be toxic and kill the cell. This prevents any modified molecules from spreading further. It is the first technology ever discovered which helps stop gene transfer from genetically-modified organisms into living things in nature.
To ensure that any escapees of the bacteria won’t survive, the team designed them to be unable to live outside a controlled lab environment. They used technology from Church Lab to make them dependent on an artificial amino acid that can only found in labs, not in nature. This allowed workers raising these bacteria – like for producing insulin -to give them this specific amino acid which they need. If anything ever got out and escaped, it wouldn’t last long since it would not be able to access things it needs to survive in open air.
So, no humans or animals will catch the so-called “superbacteria,” Nyerges explained. Nyerges is interested in using code reprogramming as a way to encourage bacteria to make special materials that would be too expensive to make through normal chemical processes. He wonders what else we’ll find out when continue exploring this area.
Robert Winthrop is a professor of genetics at the Blavatnik Institute of Harvard Medical School. Other people who worked on this project include Svenja Vinke, Regan Flynn, Kamesh Narasimhan, Jorge Marchand, Maximilien Baas-Thomas and Anush Chiappino-Pepe from HMS, Bogdan Budnik from the Wyss Institute, Eric Keen from Washington University School of Medicine, and Min Liu, Kangming Chen and Fangxiang Hu from GenScript USA Inc.
HMS recently made an official request to own a patent. Nyerges, Vinke, and Church are shown as the inventors in this application. GenScript didn’t help create any experiments for this work. Church created three different companies including GRO Biosciences, EnEvolv, and 64x Bio from which he can financially benefit.
This research was funded by the US government and a special support called ’EMBO LTF 160-2019’. They studied two things: 1. The genes of an illness that birds get, called H9N2 Avian Influenza in one particular area of China. 2. How the same flu virus acts differently in different birds around the world.
Researchers are trying to create a vaccine that can protect people from brucellosis. They are also studying rat hepatitis E virus, and they identified six strains of H5N6 highly pathogenic avian influenza virus. All of these studies will help them figure out how to best immunize against all these diseases.
