Resurrecting Ancient Proteins To Fight Back Against Modern Viruses
A Science Enthusiast
Viruses have a variety of tactics they employ in their attacks on bacteria, plants, and animals like us. Their ultimate goal is to hijack the systems of the cell and convert them into producing more of themselves. Some viruses simply reconfigure construction molecules to directly make viral parts, others insert their own viral genes into the host cell’s genome to have the normal transcription and translation machinery construct proteins for making viral systems.
The former is one of the most common, however, and usually involves hijacking an existing cellular protein and turning them into what are called proviral factors. There are also other proteins, called antiviral factors, that exist to take out their counterpart if they encounter a hijacked version. Thus, an arms race is created between bacteria and the viruses that seek to invade them.
We have methods that can assist in this resistance, such as knocking out the genes that create the hijackable proteins in the first place. But this is only an option if the proteins in question are not important for cellular function. If they are, then stopping their formation could harm the cell just as much.
Researchers at the University of Granada in Spain came up with another solution. Instead of preventing the proteins from being created, what if we instead swapped them out for proteins that cover the same function, but aren’t able to be hijacked by viruses? Where would we find such proteins, especially if we’re trying to find ones that cover the exact same function, but aren’t identical enough to just suffer the same fate as the originals?
Going Way Back
For this reason, scientists at Granada have been specializing in researching ancient bacterial genomes and the proteins those genes code for. And, by ancient, we are talking on the level of billions of years old.
Of course, DNA can’t survive that long. Heck, it can’t really survive even 10,000 years without becoming extremely degraded and damaged, no matter the preservation method. Instead, the researchers constructed phylogenetic trees for the development of certain genes and their proteins, allowing them to derive, as they put it, “plausible approximations” of the original genes used by the ancient bacterial ancestors.
Whether these sequences actually match those found in genomes of bacteria billions of years ago is more or less impossible to ascertain for sure until the day we develop time travel. But they still serve as our best guess for what kind of genes the bacteria would have had in that ancient age. It is for that reason that these have been termed as “resurrected ancestral proteins”.
Functionality Is Key
These proteins directly match the function of their modern day equivalents, since they are the same ones just passed down over billions of years. That time frame did fundamentally change them though. Even if this ancient protein is still a form of modern thioredoxin, the particular gene and protein being investigated by the Granada scientists, its form is essentially unrecognizable to viruses today.
Thus, if swapped out for the current thioredoxin protein, the cell is still capable of producing it and using it for the same function (though it should be noted that this functionality isn’t at 100%, it is still somewhat different and that lessens its effectiveness) and the bacteriophage viruses that plagued it before can no longer find a way to hijack the protein to begin their own replication process.
The researchers were, after their experiment, able to declare their E. coli with resurrected Precambrian-era thioredoxin proteins resistant to bacteriophage T7 attacks a success. This was just a first step though, a simple effort to confirm that the overall concept of reconstructing ancestral proteins was plausible and workable at all.
On To Bigger Projects
The founding goal of the research for the university was to create ancestral proteins for plants that would give them resistance to deadly viruses that harm crop harvests around the world. With proviral factors in different plants already known from other studies, their next step will be to manufacture a phylogenetic tree for whichever crop they decide to start with and begin constructing, or “resurrecting”, an ancestral protein sequence.
Improvements in bioinformatics modeling over the next few years should help to increase the speed with which they are able to construct these sequences and allow them to get to work on the real biotechnology work of swapping out the genetic sequences for their older form. The recent developments in CRISPR-Cas systems, as noted by the scientists, should make it easier to do the genetic swap-out, which was always expected to be more difficult in plants than in bacteria.
Though it’s not a slam dunk procedure just because it worked in a few tests in bacteria. It is still quite possible that the ancestral proteins will have enough lacking functionality that it will impair the overall fitness of the plant, making it unfit for actual agricultural usage. They need to find the sweet spot that allows the protein to be different enough that the viruses can’t hijack it, while also being similar enough that the functionality remains high.
Even so, the fact that they were even able to get the functionality as high as they did in bacteria is a great sign for future research. The scientists were fully expecting the proteins to not function at all and doom the experiment from the start.
But the opposite occurred, giving hope that the process of resurrecting ancestral proteins may become a new field in its own right in the fight against viral diseases.
[Study Link ](http://www.cell.com/cell-reports/fulltext/S2211-1247(17%2930531-4)
Photo CCs: Cellular-virus-wallpaper from Wikimedia Commons