A new technology called PROTEUS could change that, enabling quicker development of new vaccines and a more rapid protein evolution. This cutting-edge technology quickly creates millions of different genetic variants in large cell populations. Because of this, scientists are better equipped to address seismic biological challenges. To help make the protein evolution process more efficient, PROTEUS was designed. It breaks down timelines from years to mere weeks—a total game changer for medical research and real-world applications.
PROTEUS system, which was recently featured in a study published in the open-access journal Nature Communications. This research unveiled the vast potential of PROTEUS to address such needs. It further provided open access to its data and sequences, a rich academic resource available to the public. PERL Directed Evolution PROTEUS enables directed evolution in a single cycle. This discovery is a mammoth leap in the field of synthetic biology, particularly for the evolution of proteins linked to important tasks, such as viral resistance and drug effectiveness.
How PROTEUS Works
PROTEUS starts by designing a single gene sequence for a desired protein and engineering it into the genome of an innocuous virus. This is just the first move, keep watching to see how the story unfolds. The development uses virus-like vesicles (VLVs), which can rapidly replicate their genomes within 24 hours. In the words of one of the lead researchers working closely with PROTEUS, Christopher Denes, here’s what makes this system so important.
“Within 24 hours, these VLVs copy their genome in readiness to grow, but this copying step frequently makes mistakes, introducing mutations along the gene we want to evolve,” – Christopher Denes.
The mutations introduced during the copying process aren’t simply mistakes. They are essential players in movement towards more evolved proteins. Denes describes the process similarly to viral adaptation observed in pathogens such as SARS-CoV-2.
“Think of this as similar to how SARS-CoV-2 adapted and evolved through variants from Alpha through to Delta and now Omicron, but the selection pressure applied by our genetic problem filters out any ‘bad’ variants, amplifying the good,” – Christopher Denes.
This cyclical process of directed evolution iteratively improves and screens winning genetic variants. To that end, it increases the functionalities of proteins implicitly over generations.
Cost-Effective and Rapid Protein Evolution
One of the most exciting facets of PROTEUS is its incredible cost-effectiveness. You can go through the whole evolution process for a few thousand dollars. This affordability allows for campaigns that hit many genes at once. Each cycle of evolution only takes 24 hours, greatly compressing the research timeline.
Hopefully, this increased speed will allow researchers to get the right vaccines into development sooner. It lets them play around with a whole suite of proteins tied to functions of membranes, a space that has been difficult due to the complexity of membranous proteins.
“If it succeeds in solving this puzzle, it’ll produce more of itself. We’ve effectively linked together protein fitness with VLV survival, pretty much enforcing the survival of the fittest,” – Christopher Denes.
Kate Adamala, a University of Minnesota synthetic biologist who practices artificial evolution, echoed her excitement about PROTEUS’s capabilities.
Her perspective highlights the need for faster and more streamlined approaches in developing these critical proteins for therapeutic use.
“There are a lot of targets on a membrane’s surface, and evolving those proteins has been a pain in the lower back because they’re difficult to work with and existing processes are slow,” – Kate Adamala.
Potential Applications in Medicine
Denes remarked on this important intersection between PROTEUS and CRISPR technology:
With PROTEUS, we can now rapidly engineer custom-made CRISPR tools. This breakthrough would be monumental for genetic therapies, helping create more targeted interventions for genetic disorders. Adamala is excited to apply PROTEUS toward studying membrane proteins. This fundamental research would significantly improve our understanding of drug-drug interactions at the cellular level.
“Evolved CRISPR tools would be really valuable for both research and medicine,” – Christopher Denes.
The ability to create tailored CRISPR tools through PROTEUS could enhance genetic therapies, allowing for more precise interventions in genetic conditions. Furthermore, Adamala emphasized her interest in employing PROTEUS for membrane proteins, which could have significant implications for understanding drug interactions within cells.
“If my lab had PROTEUS, I’d start with membrane proteins because that’s a huge area and incredibly attractive from a human health perspective,” – Kate Adamala.