Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Princeton scientists construct synthetic proteins that sustain life

In a groundbreaking achievement that could help scientists "build" new biological systems, Princeton University scientists have constructed for the first time artificial proteins that enable the growth of living cells.

The team of researchers created genetic sequences never before seen in nature, and the scientists showed that they can produce substances that sustain life in cells almost as readily as proteins produced by nature's own toolkit.

"What we have here are molecular machines that function quite well within a living organism even though they were designed from scratch and expressed from artificial genes," said Michael Hecht, a professor of chemistry at Princeton, who led the research. "This tells us that the molecular parts kit for life need not be limited to parts -- genes and proteins -- that already exist in nature."

The work, Hecht said, represents a significant advance in synthetic biology, an emerging area of research in which scientists work to design and fabricate biological components and systems that do not already exist in the natural world. One of the field's goals is to develop an entirely artificial genome composed of unique patterns of chemicals.

"Our work suggests," Hecht said, "that the construction of artificial genomes capable of sustaining cell life may be within reach."

Nearly all previous work in synthetic biology has focused on reorganizing parts drawn from natural organisms. In contrast, Hecht said, the results described by the team show that biological functions can be provided by macromolecules that were not borrowed from nature, but designed in the laboratory.

Although scientists have shown previously that proteins can be designed to fold and, in some cases, catalyze reactions, the Princeton team's work represents a new frontier in creating these synthetic proteins.

The research, which Hecht conducted with three former Princeton students and a former postdoctoral fellow, is described in a report published online Jan. 4 in the journal Public Library of Science ONE.

Hecht and the students in his lab study the relationship between biological processes on the molecular scale and processes at work on a larger magnitude. For example, he is studying how the errant folding of proteins in the brain can lead to Alzheimer's disease, and is involved in a search for compounds to thwart that process. In work that relates to the new paper, Hecht and his students also are interested in learning what processes drive the routine folding of proteins on a basic level -- as proteins need to fold in order to function -- and why certain key sequences have evolved to be central to existence.

Proteins are the workhorses of organisms, produced from instructions encoded into cellular DNA. The identity of any given protein is dictated by a unique sequence of 20 chemicals known as amino acids. If the different amino acids can be viewed as letters of an alphabet, each protein sequence constitutes its own unique "sentence."

And, if a protein is 100 amino acids long (most proteins are even longer), there are an astronomically large number of possibilities of different protein sequences, Hecht said. At the heart of his team's research was to question how there are only about 100,000 different proteins produced in the human body, when there is a potential for so many more. They wondered, are these particular proteins somehow special? Or might others work equally well, even though evolution has not yet had a chance to sample them?

Hecht and his research group set about to create artificial proteins encoded by genetic sequences not seen in nature. They produced about 1 million amino acid sequences that were designed to fold into stable three-dimensional structures.

"What I believe is most intriguing about our work is that the information encoded in these artificial genes is completely novel -- it does not come from, nor is it significantly related to, information encoded by natural genes, and yet the end result is a living, functional microbe," said Michael Fisher, a co-author of the paper who earned his Ph.D. at Princeton in 2010 and is now a postdoctoral fellow at the University of California-Berkeley. "It is perhaps analogous to taking a sentence, coming up with brand new words, testing if any of our new words can take the place of any of the original words in the sentence, and finding that in some cases, the sentence retains virtually the same meaning while incorporating brand new words."

Once the team had created this new library of artificial proteins, they inserted those proteins into various mutant strains of bacteria in which certain natural genes previously had been deleted. The deleted natural genes are required for survival under a given set of conditions, including a limited food supply. Under these harsh conditions, the mutant strains of bacteria died -- unless they acquired a life-sustaining novel protein from Hecht's collection. This was significant because formation of a bacterial colony under these selective conditions could occur only if a protein in the collection had the capacity to sustain the growth of living cells.

In a series of experiments exploring the role of differing proteins, the scientists showed that several different strains of bacteria that should have died were rescued by novel proteins designed in the laboratory. "These artificial proteins bear no relation to any known biological sequences, yet they sustained life," Hecht said.

Added Kara McKinley, also a co-author and a 2010 Princeton graduate who is now a Ph.D. student at the Massachusetts Institute of Technology: "This is an exciting result, because it shows that unnatural proteins can sustain a natural system, and that such proteins can be found at relatively high frequency in a library designed only for structure."

In addition to Hecht, Fisher and McKinley, other authors on the paper include Luke Bradley, a former postdoctoral fellow in Hecht's lab who is now an assistant professor at the University of Kentucky, and Sara Viola, a 2008 Princeton graduate who is now a medical student at Columbia University.

The research was funded by the National Science Foundation.

Emily Aronson | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Don't Give the Slightest Chance to Toxic Elements in Medicinal Products
23.03.2018 | Physikalisch-Technische Bundesanstalt (PTB)

nachricht North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Space observation with radar to secure Germany's space infrastructure

Satellites in near-Earth orbit are at risk due to the steady increase in space debris. But their mission in the areas of telecommunications, navigation or weather forecasts is essential for society. Fraunhofer FHR therefore develops radar-based systems which allow the detection, tracking and cataloging of even the smallest particles of debris. Satellite operators who have access to our data are in a better position to plan evasive maneuvers and prevent destructive collisions. From April, 25-29 2018, Fraunhofer FHR and its partners will exhibit the complementary radar systems TIRA and GESTRA as well as the latest radar techniques for space observation across three stands at the ILA Berlin.

The "traffic situation" in space is very tense: the Earth is currently being orbited not only by countless satellites but also by a large volume of space...

Im Focus: Researchers Discover New Anti-Cancer Protein

An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.

The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...

Im Focus: Researchers at Fraunhofer monitor re-entry of Chinese space station Tiangong-1

In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.

Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...

Im Focus: Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.

They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

New solar solutions for sustainable buildings and cities

23.03.2018 | Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

Latest News

For graphite pellets, just add elbow grease

23.03.2018 | Materials Sciences

Unique communication strategy discovered in stem cell pathway controlling plant growth

23.03.2018 | Agricultural and Forestry Science

Sharpening the X-ray view of the nanocosm

23.03.2018 | Physics and Astronomy

Science & Research
Overview of more VideoLinks >>>