Minimalism is an increasingly popular lifestyle choice that encourages individuals to decrease the overall number of possessions owned and live more simply. According to minimalist philosophy, the reduction of unnecessary clutter enables one to live a more functional and purposeful existence. IMP-IMBA Group Leader and CSSB scientist Thomas Marlovits*, in collaboration with colleagues from Massachusetts Institute of Technology (MIT), discovered that a minimalist approach can also be applied to complex biological systems, such as the type III secretion system. The findings of this collaborative study have been published in the scientific journal, Nature Communications.
The type III secretion system (T3SS) is a needle-like molecular machine found in gram negative bacteria that transports pathogenic proteins from the bacteria to the human host cell thus initiating infection. The proteins in this system are tightly regulated and the regulatory elements of TSS3 vary greatly depending on the surrounding environment of the bacteria.
For example, Salmonella, bacteria which cause food poisoning, secretes its pathogenic proteins into human gut cells. “The question we asked ourselves is: Can we remove all of the regulatory elements from this complex biological system and re-build (refactor) the needle complex using basic genetic principles?” explains Marlovits.
To accomplish this, scientists from MIT used synthetic biology to recreate the Salmonella needle complex. Using a bottom up approach, coding and non-coding DNA was replaced or altered with synthetic parts and the scientists were able to create an ultra-simplified ‘genetic island.’ The functionality of this island was then tested in laboratories in both Boston and Vienna using conventional bio-chemistry methods. The Marlovits lab then used electron microscopy to visualize the integrity of the entire system.
“Over the course of this three year study, many rounds of debugging were needed to generate a fully functional system,” explains Marlovits “this is the first time that synthetic biology has been used successfully on such a complex system. Previous systems that have been refactored contained just three or four proteins; TSS3 is comprised of over 20 proteins.”
The development of this simplified TSS3 reveals that none of the intrinsic regulatory features of the system are required to generate a functional needle complex and can be exchanged for others. Removing this regulatory “clutter” has not only resulted in the discovery of essential functional roles played by internal start site and small RNA in but has also unveiled key insights regarding the regulatory elements themselves. Regulation, while not directly involved in function, may exist to ensure the efficient utilization of cellular resources and could also increase the number of environmental conditions under which TSS3 can function.
The refactored TSS3 could serve as new tool in biotechnology. This simplified needle complex could be inserted into other bacteria and then turned-on via a built in regulatory element that acts as a molecular switch. “TSS3 could be used as a delivery device for novel agents or vaccines,” explains Marlovits “future studies will explore the possibility of placing this refactored TSS3 into new environments.”
This minimalistic approach to understanding complex biological systems could become an essential new tool for scientists at CSSB. “Understanding how the mechanisms of host pathogen interaction impact biological systems is one of the main goals at CSSB. This new approach provides us with a unique way of looking at systems that will help us discover novel elements,” stated Marlovits.
*Thomas Marlovits is a joint group leader at the the Research Institute of Molecular Pathology (IMP) and the Institute of Molecular Biotechnology (IMBA) in Vienna. He is also affiliated with the Centre for Structural Systems Biology (CSSB), the University Medical Center Hamburg-Eppendorf (UKE), and the ‘Deutsches Elektronen-Synchrotron’ DESY in Hamburg.
Control of type III protein secretion using a minimal genetic system. Song M, Sukovich DJ, Ciccarelli L, Mayr J, Fernandez-Rodriguez J, Mirsky EA, Tucker AC, Gordon DB, Marlovits TC, Voigt CA.
Nature Communications; 2017 May 9;8:14737. doi: 10.1038/ncomms14737.
About the IMP:
The Research Institute of Molecular Pathology (IMP) in Vienna is a basic biomedical research institute largely sponsored by Boehringer Ingelheim. With over 200 scientists from 37 nations, the IMP is committed to scientific discovery of fundamental molecular and cellular mechanisms underlying complex biological phenomena. Research areas include cell and molecular biology, neurobiology, disease mechanisms and computational biology.
IMBA - Institute of Molecular Biotechnology is one of the leading biomedical research institutes in Europe focusing on cutting-edge functional genomics and stem cell technologies. IMBA is located at the Vienna Biocenter, the vibrant cluster of universities, research institutes and biotech companies in Austria. IMBA is a subsidiary of the Austrian Academy of Sciences, the leading national sponsor of non-university academic research.
About the Vienna BioCenter:
The Vienna BioCenter (VBC) is a leading life sciences location in Europe, offering an extraordinary combination of research, education and business on a single campus. About 1,600 employees, more than 1,000 students, 93 research groups, 16 biotech companies, and scientists from more than 40 nations create a highly dynamic environment. See: http://www.viennabiocenter.org/
Media Contact at IMP:
Dr. Heidemarie Hurtl
Research Institute of Molecular Pathology
+43 (0)1 79730 3625
Media Contact at IMBA:
IMBA - Institute of Molecular Biotechnology
+43 (1) 790 44-3628
Dr. Heidemarie Hurtl | idw - Informationsdienst Wissenschaft
UNH researchers create a more effective hydrogel for healing wounds
21.11.2018 | University of New Hampshire
Removing toxic mercury from contaminated water
21.11.2018 | Chalmers University of Technology
Innsbruck quantum physicists have constructed a diode for magnetic fields and then tested it in the laboratory. The device, developed by the research groups led by the theorist Oriol Romero-Isart and the experimental physicist Gerhard Kirchmair, could open up a number of new applications.
Electric diodes are essential electronic components that conduct electricity in one direction but prevent conduction in the opposite one. They are found at the...
Max Planck researchers revel the nano-structure of molecular trains and the reason for smooth transport in cellular antennas.
Moving around, sensing the extracellular environment, and signaling to other cells are important for a cell to function properly. Responsible for those tasks...
Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.
Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
19.11.2018 | Event News
09.11.2018 | Event News
06.11.2018 | Event News
21.11.2018 | Life Sciences
21.11.2018 | Medical Engineering
21.11.2018 | Physics and Astronomy