Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New Protein Manufacturing Process Unveiled

17.09.2015

Scientists now have a way to study special proteins associated with disease

Researchers from Northwestern University and Yale University have developed a user-friendly technology to help scientists understand how proteins work and how to fix them when they are broken. Such knowledge could pave the way for new drugs for a myriad of diseases, including cancer.


Michael Jewett

The human body has a nifty way of turning its proteins on and off to alter their function and activity in cells: phosphorylation, the reversible attachment of phosphate groups to proteins. These “decorations” on proteins provide an enormous variety of function and are essential to all forms of life. Little is known, however, about how this dynamic process works in humans.

Using a special strain of E. coli bacteria, the researchers have built a cell-free protein synthesis platform technology that can manufacture large quantities of these human phosphoproteins for scientific study. This will enable scientists to learn more about the function and structure of phosphoproteins and identify which ones are involved in disease.

“This innovation will help advance the understanding of human biochemistry and physiology,” said Michael C. Jewett, a biochemical engineer who led the Northwestern team.

The study was published Sept. 9 by the journal Nature Communications.

Trouble in the phosphorylation process can be a hallmark of disease, such as cancer, inflammation and Alzheimer’s disease. The human proteome (the entire set of expressed proteins) is estimated to be phosphorylated at more than 100,000 unique sites, making study of phosphorylated proteins and their role in disease a daunting task.

“Our technology begins to make this a tractable problem,” Jewett said. “We now can make these special proteins at unprecedented yields, with a freedom of design that is not possible in living organisms. The consequence of this innovative strategy is enormous.”

Jewett, associate professor of chemical and biological engineering at Northwestern’s McCormick School of Engineering, and his team worked with Yale colleagues led by Jesse Rinehart. Jewett and Rinehart are co-corresponding authors of the study.

As a synthetic biologist, Jewett uses cell-free systems to create new therapies, chemicals and novel materials to impact public health and the environment.

“This work addresses the broader question of how can we repurpose the protein synthesis machinery of the cell for synthetic biology,” Jewett said. “Here we are finding new ways to leverage this machinery to understand fundamental biological questions, specifically protein phosphorylation.”

Jewett and his colleagues combined state-of-the-art genome engineering tools and engineered biological “parts” into a “plug-and-play” protein expression platform that is cell-free. Cell-free systems activate complex biological systems without using living intact cells. Crude cell lysates, or extracts, are employed instead.

Specifically, the researchers prepared cell lysates of genomically recoded bacteria that incorporate amino acids not found in nature. This allowed them to harness the cell’s engineered machinery and turn it into a factory, capable of on-demand biomanufacturing new classes of proteins.

“This manufacturing technology will enable scientists to decrypt the phosphorylation ‘code’ that exists in the human proteome,” said Javin P. Oza, the lead author of the study and a postdoctoral fellow in Jewett’s lab.

To demonstrate their cell-free platform technology, the researchers produced a human kinase that is involved in tumor cell proliferation and showed that it was functional and active. Kinase is an enzyme (a protein acting as a catalyst) that transfers a phosphate group onto a protein. Through this process, kinases activate the function of proteins within the cell. Kinases are implicated in many diseases and, therefore, of particular interest.

“The ability to produce kinases for study should be useful in learning how these proteins function and in developing new types of drugs,” Jewett said.

The National Institutes of Health (grants NIDDK-K01DK089006 and P01DK01743341), the Defense Advanced Research Projects Agency (grant N66001-12-C-4211) and the David and Lucille Packard Foundation Fellowship supported the research.

The title of the paper is “Robust production of recombinant phosphoproteins using cell-free protein synthesis.” The other co-first author is Hans R. Aerni, of Yale.

Megan Fellman | Northwestern University
Further information:
http://www.northwestern.edu/newscenter/stories/2015/09/jewett-new-protein-manufacturing-process-unveiled.html

More articles from Life Sciences:

nachricht Bare bones: Making bones transparent
27.04.2017 | California Institute of Technology

nachricht Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Bare bones: Making bones transparent

27.04.2017 | Life Sciences

Study offers new theoretical approach to describing non-equilibrium phase transitions

27.04.2017 | Physics and Astronomy

From volcano's slope, NASA instrument looks sky high and to the future

27.04.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>