Israeli scientists to work together, using ultrasensitive nuclear magnetic resonance (NMR) technology to speed up the new crown pneumonia virus RNA research

Lucio Frydman professor in nuclear magnetic resonance (NMR) has excellent practical experience, 15 years ago in his career, he has been built to use their instruments.Even worked in this field for more than 30 years, professor Frydman enthusiasm for NMR technique.As he puts it: "I'm always excited to see what each day will bring different."Last year, as part of a study of SARS - CoV - 2 (the virus that causes the new crown pneumonia) RNA structure research alliance, professor Frydman and his team have a lot of new discovery.

Nuclear magnetic resonance (NMR) a common language in the industry

In Israel's Weizmann Rehevot science institute, with 250 team, covering everything from biology, biochemistry and chemical, to all the disciplines in the physics, mathematics and computer science.The institute has been the earliest use of instruments and equipment of the new progress of one of the institutions.These instruments including superconducting 270 MHz () in different periods of a nuclear magnetic resonance (NMR), a spectrometer, 800 MHz system, a 7 T mri scanner, a 15.2 T mri scanner, animal, and the most relevant working with professor Fryman RNA 1.0 GHz brooke nuclear magnetic resonance spectrometer.

Professor Frydman described his work as including two complementary areas.One of the first field is the nuclear magnetic resonance (NMR) as a discipline to study.For example, nuclear spin behavior in certain situations, and how to improve the analytical sensitivity, resolution and speed.Another aspect is the practical application of this technology, professor Frydman team in different domains such as materials, medicines, RNA and cancer work [1].

As professor Fryman points out, however, whatever the application, all of the nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) the experiment is based on the same basic physical processes, through radio frequency (rf) pulse, cleverly disrupt the nucleus and the electron spin will achieve balance in the strong magnetic field.Such as professor Fryman puts it, this kind of "common language" intersection of ideas in a special way.For example, he said: "you can apply for imaging and the development idea to · · · · · · chemical or apply for solid experiment development methods to the molecules in cells."

A concerted effort to study new crown pneumonia

The concept of "intersection" core of professor Fryman work recently, also as part of Covid - 19 nuclear magnetic resonance (NMR) [2].This consists of more than 50 research groups from all over the world alliance to determine new crown pneumonia virus RNA structure, to determine whether the protein can use nuclear magnetic resonance (NMR) spectrum analysis, and in this process by its small molecular characterization provide insight into the "medicinal property (drugability)".

Frydman professor has joined Covid - 19 nuclear magnetic resonance (NMR), originated from his previous contact of the johann Wolfgang Goethe university of Frankfurt, Germany.This work mainly involves improving sensitivity and speed of RNA analysis, therefore, when Goethe university Harald Schwalbe professor Dr Founded in March 2020, the alliance, he naturally become collaborators.To join the team, professor Frydman quickly will shift the focus to research the SARS - CoV - 2 large RNA genome, using 2018 installed at the Weizmann institute of 1 GHz brooke nuclear magnetic resonance spectrometer, and other instruments.

The work is essentially a collaborative, Frydman, said professor this cooperation has brought the very positive impact: "we have been sharing samples, method, database, the experimental results, and so on...All these help us develop a user friendly way, in order to extract high sensitivity data more quickly."

All of these highly sensitive data to make us for SARS - CoV - 2 have a better understanding of the genome, including many parts of the level and structure of RNA secondary structure has carried on the qualitative [3], and found several can combine with RNA targets of potential drugs.In terms of his own, professor Frydman emphasized on the benefits of such a challenging task: "in the face of difficulties brought by the new crown pneumonia let's attention to the performance of the existing tools.In addition to help us understand the SARS - CoV - 2 RNA structure, these tools are likely to eventually find applications in other fields, and that is the nature of the nuclear magnetic resonance (NMR)."

Using the high sensitivity of nuclear magnetic technology exquisite detail processing

Professor Frydman particularly keen on a tool is nuclear hyperpolarization [4, 5].In short, it involves the radical groups during the height of the electron spin polarization transfer to water or small molecules of 13 c nuclear spin.This is in low temperature, high magnetic field and carried out under microwave irradiation.As a result, the nucleus is polarization, the degree of several orders of magnitude larger than under normal circumstances, this, in turn, means that they can be in in vitro and in vivo experiments carried out under very low concentration needed for research.

Frydman professor emphasized that it is scientific discovery, eventually realize the application value of an unexpected example: "nuclear hyperpolarization known for 60 years, in 40 years before, it is to a great extent, but the scientists a curiosity.But now, it has found some specific applications, and this is only one instance out of many, this area very basic knowledge about behavior of elementary particles eventually led to the biological macromolecules and metabolism in study practical insights."

The team found in the research work in the new crown pneumonia another technique involves a series of magnetization transfer experiment [6, 7, 8], it overcomes the trying to use NOESY and related technologies to determine amino or the proximity of amino and adjacent proton encountered during peak resolution problem of low sensitivity and bad.High resolution of the method, especially in the field, with the traditional sampling method, but its sensitivity is greatly enhanced.Based on the method of magnetization transfer also enables the experiment at higher temperature, to study the physiological conditions of RNA structure opens up prospects.

To do a good job, must first sharpen his device

"The technology is a new technology to promote social better results of two examples," professor Frydman added, "in the field of science has a" pyramid "- better tools can bring better sensitivity and faster speed, enable people to research in more realistic conditions more diverse sample, this, in turn, to promote a better understanding of natural systems."

So the future will be how?So far, professor Frydman within the alliance's priority is to get the basic understanding of RNA genome, by RNA cut into smaller pieces and independent research."The challenge now is to know the decodes the mechanism of action of drugs, and study the RNA of the larger, more dynamic.Especially, we want to see whether their structure, activity and drug combination mode be preserved, especially at higher temperatures, professor Frydman said."

Brooke to provide expert technical support

Frydman, says professor in Covid - 19 before and during the project, brooke's contribution is crucial: "the Weizmann institute since the 1970 s has been brooke's customers, but for the first time I use their instruments was about 8 years ago.My experience is very good, very thank brooke have done.From the beginning, they gave me a lot of help, let my old machines and brooke's new instrument integrated workflow, in the next few years, they also continued to provide professional technical support."

Professor Frydman went on to say: "nuclear magnetic resonance (NMR) is gradually becoming a more mature science, at any time may slow speed of technological development.In order to keep the nuclear magnetic resonance (NMR) spectroscopy, evergreen, continue to benefit society, we must constantly strive for more achievements.In this regard, it is meaningful to have cooperation with brooke.They have a first-class scientists, excellent equipment, their work is also the highest standards.Together we solve the new problems, and to keep each other in the forefront of science.They are indeed 'the experts'."

Contingency, curiosity and common goals

Professor Frydman keen to emphasize another theme is the cooperation in the field of scientific value."Covid - 19 league for sharing data, results, and idea provides a strong reason, which means that often takes years to achieve development has became more and more fast."He added this cooperation is quite natural: "compared with other research areas, nuclear magnetic resonance (NMR) is actually a pretty college spirit field.I think the transparency in the league has been further strengthened, I hope we in the past year some of the works will always continue, even if the new crown pneumonia gradually disappear."

Nevertheless, he work for the future or realistic attitude: "research progress in the new crown pneumonia will need a lot of hard work, at least for me, need powerful magnets and a large amount of data processing.But we must also admit that chance and curiosity in the field of research, we must be willing to accept surprising observed, or thinking problems in unconventional ways.Covid - 19 league is wonderful in that it makes it easier, because our hearts have a clear goal, and we are ready to share our best ideas to make progress."

Fryman professor put forward about the cooperation value is derived from the past year life brought him the ultimate thinking: "as a scientist, of course, we have a lot in common, but let's see, as humans, we also have a lot in common.Therefore, we in this league using nuclear magnetic resonance (NMR) research new crown pneumonia virus cooperation way should motivate us to co-operate in other areas, in order to solve the problem of affects everyone on earth.

For more Covid - 19 NMR union information, please visit:https://covid19-nmr.de/You can also watch more members interview://www.videcame.com/en/products-and-solutions/mr/make-mr-more-relevant/covid19-nmr-consortium.html

For more information about Fryman group, please visit:https://www.weizmann.ac.il/chembiophys/Frydman_group/

Lucio FrydmanProfessor is located in Rehovot, Israel's Weizmann institute of science of chemical and biological, director of the department of physics, he has been working there since 2001.He is also located in the United States in Tallahassee, Florida chemistry and biology, chief scientist of the country's high field laboratory.

Professor Frydman has published more than 250 peer-reviewed papers, and from 2011 to 2020, served as chief editor of the journal of magnetic resonance (NMR).He is currently the JMR - founding editor of Open, this is the form a complete set of journal of magnetic resonance (NMR).

1. For more about the work of the initial Frydman group, visithttps://www.weizmann.ac.il/chembiophys/Frydman_group/home
2. For more about the Covid - 19 consortium, visithttps://covid19-nmr.de/
3. A. Wacker et al., Secondary structure determination of conserved SARS - CoV - 2 RNA elements by NMR spectroscopy, Nucleic Acids Research, 2020, 48, 12415-12435.
4. Fages, s. Markovi level, a. t. Roussel, r. Hadas, a. Brandis, m. Neeman and l. Frydman, Maternal - fetal exchanges and placenta metabolism followed in real - time by dynamic 13 c hyperpolarized MRSI, Proc. Natl. Acad tools. Sci. USA, 2018;115 (10) E2429 - E2436.
   
5. M. Novakovic, g. g. Olsen, Pinter, d. Hymon, b. Furtig, h. Schwalbe and l. Frydman, > 300 - fold enhancement of imino nucleic acid resonances via hyperpolarized water: A new window for probing RNA refolding by 1 D and 2 D NMR;By Proc. Natl. Acad. Sci. USA, 2020;117, 5, 2449-2455.
6. J. Kim et al., 3 d Heteronuclear magnetization transfers for the establishment of secondary structures in SARS - CoV - 2 - derived RNAs, Journal of the American Chemical Society, 2021, 143:4942-4948.
   [7] m. Novakovic et al., Magnetization transfer to enhance NOE cross - peaks among labile protons: Applications to imino - imino sequential walks in COVID - derived RNAs, Angewandte Chemie International Edition, 2021 (accepted article).
7. M. Novakovic, e. Kupce, a. Oxenfarth, m.d., Battistel, D.I. Freedberg, h. Schwalbe., and l. Frydman, Hadamard magnetization transfers your this sensitivity to enhancements in homonuclear multidimensional NMR correlations of labile sites in proteins, polysaccharides and nucleic acids, Nat Comm, 2020;11, 5317, (2020).
   
   

The Weizmann institute in Rehovot, Israel since 1952 has been at the forefront of nuclear magnetic resonance (NMR) research, then by Saul Meiboom leadership team built the world's first batch of one of nuclear magnetic resonance spectrometer.Now, the study of all 12 nuclear magnetic resonance (NMR) research team, involved in areas such as from the detection of single molecule to the brain functional magnetic resonance imaging (fmri).

Brooke is committed to supporting scientists acquire the groundbreaking scientific discoveries and new applications are developed to improve the quality of life of human beings.Brooke's science and technology of high performance instruments and high value analysis and diagnosis of solution, allow scientists to the molecules, cells and micro level to explore the mysteries of life and material.In close cooperation and user, brooke devotes to the scientific and technological innovation, improve productivity and achieve the success of the user.Our business areas include molecular life science research, and drug application, microscope and nanometer analysis, industrial application, cell biology, preclinical imaging, clinical phenotype omics, proteomics research and clinical microbiology and so on.