Nordic Life Science 1
SCIENCE REPORT RESEARCH NEWS FROM THE NORDIC REGI
ON the CSX1 starts cutting up the intruder. We can see how CSX1 is activated, rotates and starts defending the cell once COA is activated,” says Guillermo Montoya, Professor at the Novo Nordisk Foundation Center for Protein Research at the Faculty of Health and Medical Science. The researchers have also managed to successfully activate the process themselves. They sent a COA molecule after the protein complex, so to speak, and thus started the defense mechanism. “In short, we have found a switch that turns on the cell’s defense system when we want it to, and so we can diffuse possible attacks,” says Montoya. “It is the first time ever that researchers have managed to map and activate a bacterial immune system.” The defense system in bacteria resemble in many ways the human innate immune system. “Therefore, it is also a step along the way to understanding the human immune system better, as well as knowing how to fight bacteria and defend oneself against viruses, and in the long run even multiple resistance,” says Montoya. CRYO-EM The discovery of a bacteria defense system was made possible using X-ray crystallography at an establishment in Switzerland and one of the world’s most powerful microscopes, the synchrotron MAX IV in Lund, Sweden. The image of the CSX1protein complex was made possible by the advanced cryogenic electron microscope at the University of Copenhagen’s CryoEM facility. “Cryo-EM played a very important role, as we could not solve the phase problem by the standard methods to solve the atomic structure of this protein. We used cryoEM to determine an initial model of this complex. This initial model could be used in a technique called molecular replacement to solve the crystal structures. Without the cryoEM map it was near to impossible to solve the crystal structures. I think this is a good example of how to combine X-ray crystallography with cryoEM,” says Montoya. There are many possible angles for continuing this research, says Montoya. “In principle, we would like to explore the possibility of using this RNase in molecular diagnostics, but the fact that it can be switched on by a small molecule (cyclic oligoadenylate), which can be also degraded by ring nucleases, might open the door to using these protein modules as part of a gene expression circuit. We will also continue to explore the molecular mechanisms of other CRISPR-Cas proteins, as the sequencing of different prokaryotes is discovering a plethora of new members of these types of polypeptides.” THE MONTOYA RESEARCH GROUP AT THE NOVO NORDISK FOUNDATION CENTER FOR PROTEIN RESEARCH AT THE FACULTY OF HEALTH AND MEDICAL SCIENCE GUILLERMO MONTOYA SWEDEN THE SCHEELE AWARD GOES TO THE DISCOVERER OF CRISPR/CAS9 THE SCHEELE AWARD 2019 PRIZE-WINNER IS PROFESSOR EMMANUELLE CHARPENTIER, MAX PLANCK UNIT FOR THE SCIENCE OF PATHOGENS, BERLIN. N HONOR OF the worldrenowned Swedish chemist and pharmacist Carl Wilhelm Scheele, the Swedish academy of Pharmaceutical Sciences has since 1961 bestowed the Scheele Award on prominent scientists in the field of drug research or related disciplines. By tradition the award ceremony is accompanied by a symposium carrying the signature of the prize-winner. In 2012 Jennifer Doudna at the University of California, Berkeley, and Emmanuelle Charpentier at the University of Vienna and the University of Umeå, published their groundbreaking findings about the mechanisms behind the CRISPR/ Cas 9 system. CRISPR/Cas9 is a machinery that naturally occurs inside certain bacteria. Its purpose is to destroy foreign DNA chains. This discovery has enabled possibilities to change the DNA of organisms. This is a revolution within gene technology that provides possibilities among other things to cure diseases and alter plants so that they are more resistant. Emmanuelle Charpentier NORDICLIFESCIENCE.ORG 89 PHOTO HALLBAUER&FIORETTI PHOTO NOVO NORDISK FOUNDATION PHOTO SIMOM SKIPPER