Jekyll2023-09-04T15:05:32+00:00http://unmr-nl.science.uu.nl/feed.xmluNMR-NLThis is the website of the ultrahigh-field NMR facility for the NetherlandsVlad CojocaruNewly discovered antibiotic kills bacteria in an unusual manner and may be hard to rezist2023-09-04T00:00:00+00:002023-09-04T00:00:00+00:00http://unmr-nl.science.uu.nl/news/Discovery_of_a_new_antibiotic<p><img src="/assets/images/posts/news/2023-09-04_news_image_01.jpg" alt="Post Image" /></p>
<p><em>Image: Mechanism of action of the newly discovered antibiotic Clovibactin</em></p>
<p>Researchers at Utrecht University lead by Markus Weingarth (https://www.weingarth-group.org/) and collaborators from Bonn University (Germany), the German Center for Infection Research (DZIF), Northeastern University of Boston (USA), and the company NovoBiotic Pharmaceuticals (Cambridge, USA) discovered a new powerful antibiotic, isolated from bacteria that could not be studied before, that seems to be capable of combating harmful bacteria and even multi-resistant ‘superbugs’. Named Clovibactin, the antibiotic appears to kill bacteria in an unusual manner, making it more difficult for bacteria to develop any resistance against it. The discovery of Clovibactin and its killing mechanism was published in the scientific journal Cell.</p>
<p><a href="https://www.uu.nl/en/news/new-antibiotic-from-microbial-dark-matter-could-be-powerful-weapon-against-superbugs">Read more</a></p>
<h3 id="publication">Publication:</h3>
<p><strong>An antibiotic from an uncultured bacterium binds to an immutable target</strong><br />
<em>Rhythm Shukla, Aaron J. Peoples, Kevin C. Ludwig, Sourav Maity, Maik G.N. Derks, Stefania De Benedetti, Annika M Krueger, Bram J.A. Vermeulen, Theresa Harbig, Francesca Lavore, Raj Kumar, Rodrigo V. Honorato, Fabian Grein, Kay Nieselt, Yangping Liu, Alexandre Bonvin, Marc Baldus, Ulrich Kubitscheck, Eefjan Breukink, Catherine Achorn, Anthony Nitti, Christopher J. Schwalen, Amy L. Spoering, Losee Lucy Ling, Dallas Hughes, Moreno Lelli, Wouter H. Roos, Kim Lewis, Tanja Schneider, Markus Weingarth</em><br />
Cell, 22 August 2023, <a href="https://doi.org/10.1016/j.cell.2023.07.038">doi: 10.1038/s41586-022-05019-y</a></p>Vlad CojocaruComputer simulations visualize how stem cell protein opens wrapped DNA2022-09-28T00:00:00+00:002022-09-28T00:00:00+00:00http://unmr-nl.science.uu.nl/news/Computer-simulations-visualize-how-stem-cell-protein-opens-wrapped-DNA<p>A key protein for converting adult stem cells into cells that resemble embryonic stem cells has been visualized in unprecedented detail by an international team of researchers. By combing experiments and computer simulations, the team visualized how the Oct4 protein binds and opens short pieces of DNA while wrapped around nuclear storage proteins (histones), just like in our genome. The team was led by Vlad Cojocaru from the University of Utrecht (the Netherlands) and the Babeş-Bolyai University of Cluj-Napoca (Romania) and Hans Schöler from the Max Planck Institute for Molecular Biomedicine in Münster (Germany). The researchers publish their results in the journal Nucleic Acids Research on 22 September 22.</p>
<p><a href="https://www.uu.nl/en/news/computer-simulations-visualize-how-stem-cell-protein-opens-wrapped-dna">Read more</a></p>
<h3 id="publication">Publication:</h3>
<p><strong>OCT4 interprets and enhances nucleosome flexibility</strong><br />
<em>Caitlin M MacCarthy, Jan Huertas, Claudia Ortmeier, Hermann vom Bruch, Daisylyn Senna Tan, Deike Reinke, Astrid Sander, Tim Bergbrede, Ralf Jauch, Hans R Schöler, Vlad Cojocaru</em><br />
Nuclei Acids Research, 22 September 2022.
DOI: <a href="http://dx.doi.org/10.1093/nar/gkac755">10.1093/nar/gkac755</a></p>
<p><em>Image: Native genomic nucleosomes bound (dark blue) by Oct4 (red) and in free form (yellow). The surfaces and ribbons illustrate the DNA and the core structured regions of the histones respectively. Oct4 stabilizes a partially open form of one nucleosome (on the right) and induces a large opening in the other (on the left). Oct4’s impact on the structures of these nucleosomes depends on the mobility of the flexible histone tails (gray and light blue in free and Oct4-bound nucleosomes respectively) and of its two subdomains (red) that bind to different faces of DNA. The background shows colonies of human induced pluripotent cells cultured on feeder cells (lower left corner) and derived from human skin cells by the induction of the indispensable Oct4 and three other proteins. The pictures were created with VMD (http://www.ks.uiuc.edu/Research/vmd/) by Vlad Cojocaru and the background image was kindly provided by Sergiy Velychko (MPI Münster).</em></p>Vlad CojocaruA key protein for converting adult stem cells into cells that resemble embryonic stem cells has been visualized in unprecedented detail by an international team of researchers. By combing experiments and computer simulations, the team visualized how the Oct4 protein binds and opens short pieces of DNA while wrapped around nuclear storage proteins (histones), just like in our genome. The team was led by Vlad Cojocaru from the University of Utrecht (the Netherlands) and the Babeş-Bolyai University of Cluj-Napoca (Romania) and Hans Schöler from the Max Planck Institute for Molecular Biomedicine in Münster (Germany). The researchers publish their results in the journal Nucleic Acids Research on 22 September 22.van Ingen lab and collaborators discover a new way to assemble chromatin2022-08-19T00:00:00+00:002022-08-19T00:00:00+00:00http://unmr-nl.science.uu.nl/news/vanIngen-lab-discovers_new_ways_to_wrap_DNA<p><img src="/assets/images/posts/news/2022-08-19_news_image_01.jpg" alt="Post Image" /></p>
<p><em>Image: The tructure of APLF (magenta), bound to the histone complex.</em></p>
<p>A team of researchers led by the <a href="www.vaningen-nmr.nl">group of Hugo van Ingen</a>, discovered a novel mechanism by which nucleosomes, the building blocks of chromatin, can be assembled. Nucleosomes are made by carefully controlled process in which different histone proteins are deposited step-by-step on the DNA through different chaperone proteins.</p>
<p>The chaperone protein APLF can assemble the nucleosome single-handedly in one step, the researchers write in the scientif journal <a href="www.science.org/journal/sciadv">Science Advances</a>. As the APLF protein is part of the DNA repair process, this unique mechanism could be means to maintain epigenetic information during DNA repair.</p>
<p>PhD student Ivan Corbeski in the van Ingen group used NMR and other experiment to discover that APLF can bind and assemble all four core histone proteins simultaneously,. Together with the Sixma group at the Netherlands Cancer Institute NKI the crystal structure of the APLF-histone complex could be solved, showing that APLF assembles the histones in their native fold as in the nucleosome.</p>
<p>The group of Francesca Mattiroli at teh Hubrecht Institute could then show that APLF can transfer the histones via this complex to the DNA to form nucleosomes. These findings were then confirmed in cellular experiments in the group of Haico van Attikum at Leiden University Medical Centre.</p>
<p><a href="www.vaningen-nmr.nl">Read more</a> about research in the lab of Hugo van Ingen</p>
<h3 id="publication">Publication:</h3>
<p><strong>Chaperoning of the histone octamer by the acidic domain of DNA repair factor APLF</strong><br />
<em>Ivan Corbeski, Xiaohu Guo, Bruna V. Eckhardt, Domenico Fasci, Wouter Wiegant, Melissa A. Graewert, Kees Vreeken, Hans Wienk, Dmitri I. Svergun, Albert J. R. Heck, Haico van Attikum, Rolf Boelens, Titia K. Sixma, Francesca Mattiroli, Hugo van Ingen</em><br />
SCIENCE ADVANCES, 27 Jul 2022, Vol 8, Issue 30
DOI: <a href="www.doi.org/10.1126/sciadv.abo0517">10.1126/sciadv.abo0517</a></p>Vlad CojocaruThe Weingarth lab discovers new ways ‘young’ antibiotics kill bacteria2022-08-05T00:00:00+00:002022-08-05T00:00:00+00:00http://unmr-nl.science.uu.nl/news/Weingarth-lab-discovers_a_new_way_antibiotics_kill_bacteria<p><img src="/assets/images/posts/news/2022-08-05_news_image_01.jpg" alt="Post Image" /></p>
<p><em>Image: Long fibrils of teixobactin (yellow arrows) and lipid II (red-blue dots) lead to weak spots in the cell membrane of the bacterium. Image: Barth van Rossum.</em></p>
<p>The <a href="https://www.weingarth-group.org/">Weingarth lab</a> at <a href="https://www.uu.nl">Utrecht University</a> discovered a new mechanism of how antibiotics kill bacteria. The antibiotic teixobactin uses a dual molecular strategy: it blocks the bacterial cell wall synthesis and destructs the cell membrane, the researchers write in the scientific journal Nature. The new insights could enable the design of powerful antibiotics against which bacteria do not readily develop resistance.</p>
<p>“Bacteria need a special lipid called lipid II to build their protective envelope around them. We show at atomic level that teixobactin targets and sequesters lipid II. Afterwards, teixobactin and lipid II together form long fibrils on bacterial cell membranes,” says Markus Weingarth. “Gradually, this creates a kind of valley in the landscape of the cell membrane, which then breaks down and damages the membrane.” The Utrecht researchers turned out to have found a biomolecular mechanism that was unknown to science until now. “It is a unique killing strategy.”</p>
<p><a href="https://www.uu.nl/en/news/youngest-antibiotic-kills-bacteria-via-a-new-two-step-mechanism">Read more</a></p>
<h3 id="publication">Publication:</h3>
<p><strong>Teixobactin kills bacteria by a two-pronged attack on the cell envelope</strong><br />
<em>Rhythm Shukla, Francesca Lavore, Sourav Maity, Maik G.N.Derks, Chelsea R. Jones, Bram J.A. Vermeulen, Adéla Melcrová, Michael A. Morris, Lea Marie Becker, Xiaoqi Wang, Raj Kumar, Joâo Medeiros-Silva, Roy A.M. Van Beekveld, Alexandre M.J.J. Bonvin, Joseph Lorent, Moreno Lelli, James Nowick, Harold D. MacGillavry, Aaron J. Peoples, Amy L. Spoering, Losee L. Ling, Dallas E. Hughes, Wouter H. Roos, Eefjan Breukink, Kim Lewis, and Markus Weingarth</em><br />
Nature, 3 August 2022, <a href="https://www.nature.com/articles/s41586-022-05019-y">doi: 10.1038/s41586-022-05019-y</a></p>Vlad CojocaruUtrecht University2022-07-05T00:00:00+00:002022-07-05T00:00:00+00:00http://unmr-nl.science.uu.nl/organization/partners/Utrecht_University<h2 id="utrecht-university"><a href="https://www.uu.nl/en/research/nmr">Utrecht University</a></h2>
<p>The NMR group at Utrecht University focuses on high-resolution solid-state (Baldus, Weingarth) and liquid-state NMR (van Ingen), as well as on computational studies of biomolecules and their interactions (Bonvin). The research aims at gaining fundamental insight into biological processes using NMR in combination with molecular biology and computational structural biology methods.</p>
<p>Novel research concepts are being developed and applied to complex biomolecular systems in the context of diseases such as cancer or Alzheimer’s disease and for the development of novel antibiotics or biomaterials including drug carriers or artificial tissues.</p>Vlad CojocaruUtrecht UniversityUniversity of Wageningen2022-07-04T00:00:00+00:002022-07-04T00:00:00+00:00http://unmr-nl.science.uu.nl/organization/partners/Wageningen-University<h2 id="wageningen-university"><a href="https://www.wur.nl/en/product/NMR-ESR-and-MRI-research-facilities-1.htm">Wageningen University</a></h2>
<p>Academic groups as well as applied research groups from the WUR operate in different fields of nuclear magnetic resonance: (low-field, time domain) relaxation, (micro-)imaging and (high-resolution) spectroscopy, as well as electron resonance spectroscopy. The key groups the Wageningen MAGNEtic resonance research FacilitY (MAGNEFY) are BioNanoTechnology (Velders) and BioPhysics (van Duynhoven). Both groups develop in-house MR-hardware parts such as dedicated gradient systems, rheo-MRI cells, as well as tailor-made pulse sequences.</p>
<p>Research expertise of the BioNanotechnolgy group reaches from characterization of nanomaterials and complex self-assembled superstructures to small volume NMR. The BioPhysics group has a track record in development and application of NMR/MRI methods to plant-MRI and complex food systems.</p>Vlad CojocaruWageningen UniversityRadboud University2022-07-03T00:00:00+00:002022-07-03T00:00:00+00:00http://unmr-nl.science.uu.nl/organization/partners/Radboud-University<h2 id="radboud-university"><a href="https://www.ru.nl/science/magneticresonance/">Radboud University</a></h2>
<p>The Nijmegen solid-state NMR group (Kentgens, van Eck, Tessari) combines the study of materials with NMR methodology and technology developments ranging from groundbreaking microfluidic probe technology and liquid-state DNP concepts, pulsed methods to study quadrupolar nuclei, to solid-state micro MAS technology. The materials under investigation are all placed in a societally relevant context, such as materials for the generation and storage of energy, solar cell materials, efficient catalysts, pharmaceuticals and drug-delivery systemsand polymeric materials from engineering plastics to high performance plastics.</p>Vlad CojocaruRadboud UniversityLeiden University2022-07-02T00:00:00+00:002022-07-02T00:00:00+00:00http://unmr-nl.science.uu.nl/organization/partners/Leiden-University<h2 id="leiden-university"><a href="https://www.universiteitleiden.nl/en/research/research-facilities/science/nmr-facility#tab-1">Leiden University</a></h2>
<p>Leiden University houses NMR groups with a focus on high resolution NMR on proteins and enzyme-ligand interactions (Ubbink), solid-state NMR on natural and artificial photosynthetic systems (de Groot, Pandit, Alia, Buda) and MRI and MR spectroscopy (Alia). The Ubbink group has a unique position in research and development of paramagnetic NMR to study structures, dynamics and interactions of biomacromolecules and since 2013, LU houses the paramagnetic NMR facility. Research at the solid-state NMR groups focuses on resolving principal mechanisms of photosynthesis. The group actively contributes to the development of HR-MAS, micro-imaging and in-situ NMR for a molecular view of energy regulation and storage in intact plants and algae.</p>Vlad CojocaruLeiden UniversityTI-COST2022-07-01T00:00:00+00:002022-07-01T00:00:00+00:00http://unmr-nl.science.uu.nl/organization/partners/TI-COST<h2 id="ti-cost"><a href="https://www.ti-coast.com/">TI-COST</a></h2>
<p>Analytical science plays a crucial role in economic and societal dynamics in the Netherlands. Positioned between fundamental sciences and final application, analytical science is at the heart of innovation. COAST aims to advance Dutch excellence in its topsectors by providing pivotal analytical knowledge and instruments based on fundamental science and by ensuring transfer of analytical expertise between application areas.</p>
<p>Innovating analytical science and technology, connecting education and unlocking state-of-the-art research facilities to serve application areas and promote new economic activities.</p>
<p>COAST participants are both public and private organisations that develop or apply innovative analytical techniques.</p>Vlad CojocaruTI-COSTAd Bax2022-06-30T00:00:00+00:002022-06-30T00:00:00+00:00http://unmr-nl.science.uu.nl/organization/board/board-members/Ad-BaxVlad Cojocaru