Sven enjoyed the NVBMB spring symposium

By: Sven Hennig

On Friday, 12.05.2023 the 2023 NVBMB Spring Symposium was held in Groningen. The topic of this spring centered around Recent Advances Structural Biology and included many scientific achievements using different techniques and sub-types of Crystallography, NMR and Electron Microscopy.  I was invited to give a talk on our developments in modulating transcription factor protein-protein interactions (Jeganathan & Wendt et al.) and was happy to join. The Spring Symposium also served as a kick-off meeting for the Structural Biology Platform (centered around Dirk Slotboom, Bert Janssen and Albert Gustkov), an interest group of Dutch structural biologist established in 2023 and serving as a platform to organize, discuss and exchange.

The NVBMB chair Luc Brunsveldt used the chance and valued the PhD work of Rebecca Halbach (Ronald van Rij and Pascal Miesen, Dept. Medical Microbiology and the Radboudumc Research Institute of Radboudumc) on piRNAs on vector mosquitos by awarding her the Westenbrink Price.

Overall a very nice event, well organized and full of scientific an structural interactions.

On the photo you see all people that provided a talk or otherwise contribution to the NVBMB spring symposium.

Report of ECM33 in Versailles by Loes

The 33 European Crystallographic Meeting (ECM33) was held in the Palais des Congres from 23-27 August in Versailles. As always, a broad range of microsymposia was offered that were proposed and organized by the SIGs and Gigs (special/general interest groups) of the ECA. In addition, there were 16 keynote and 2 plenary lectures. The subjects range from the X-ray investigation of batteries for energy storage, total scattering studies and diffuse scattering, crystal engineering, quantum crystallography,  software development, 3D electron diffraction, large scale facilities, serial crystallography and time resolved studies as well as fold prediction of proteins. The commercial exhibitions allow one to get informed on the latest developments in equipment and techniques. Many of the companies are indispensable sponsors for the ECM organization.

The building presented a challenge to find the lecture rooms, with many stairs leading to the wrong side of the building and even the wrong floor. Apart from that the location was superb, just opposite the Chateau de Versailles, which is amazingly large, even if you know that.

This year it was the celebration of 25th anniversary of the ECA. There was a special celebration session, where almost all of the past presidents said a few words about their experiences. The session started with our member Paul Beurkens who was one of the co-founders of ECA. It was a great achievement to remodel the somewhat loose ECC that had been responsible for organizing the ECMs before. As it happened it was (almost) 50 years ago that the first ECM was held in Bordeaux. The ECA has national members, which are usually national crystallographic associations, like our NVK. Aside from that, crystallographers can also become individual members, and these are entitled to become member of the SIGs and have some other privileges.

There were almost 900 participants, so that is a success for the organization. It was very rewarding to meet colleagues in person again, after all the corona restrictions.

By: Loes Kroon-Batenburg

Canan Durukan enjoyed summer school at MAX-IV

Hello from Amsterdam! My name is Canan Durukan. Right after obtaining my master’s degree in Chemistry in Istanbul, Turkey, I started my PhD in Sven’s Lab at VU Amsterdam in summer 2020. My research focus is on bimolecular interactions and their modifications, specifically for protein-protein interaction modifications of the NF-Y transcription factor. The major part of my work so far was the study of proteins and ligand binding. It is both interesting and fun to carry out research about proteins and discover this complex world of proteins and crystallography.

Last June I attended a summer school about data collection and structure determination in macromolecular crystallography at MAX IV which is organized by MAX IV Laboratory and Aarhus University. There were both theoretical lectures given by international experts and practical exercises. It was pretty exciting and inspiring to be among the participants and have a chance to meet a group of experts in their field with great insights and having heard about their knowledge and experiences as well as being at a synchrotron and meeting beamline scientists. I do believe that these organizations, in which scientists from different places come together for sharing and exchanging knowledge, are very encouraging and valuable. We are mostly focused on our own work and these occasions help us step back and consider the big picture by seeing what everyone else is doing.

I joined the  NVK Young Researchers Retreat last September. It was nice to meet researchers in Dutch crystallography association in person.

Bio: Canan graduated from Yildiz Technical University, Turkey with a bachelor’s degree in Chemistry. She then started her Master’s studies in polymer chemistry at Istanbul Technical University. After her graduation in the summer 2020, she started her PhD in Sven’s lab at the beginning of August 2020 to work on understanding protein-protein interactions and their modifications.

Merry Christmas & a happy new year!

We really enjoyed meeting our members again at the symposium, and are very happy that we have welcomed a group of new members! Looking forward to meeting you after the holidays!

 

Inaugural lecture Dr. Raimond Ravelli – Nov. 18. 2022

Former chair of the NVK, Dr. Raimond Ravellli, will provide his inaugural lecture to be appointed Professor in Structural Biology on Friday November 18th, 2022 at Maastricht University. The title of this lecture is “Musing on Nanobiology” and will also be broadcasted through a live-stream. Please find more information here.

On his inauguration, Raimond Ravelli showed a beautiful animation of the SARS-CoV-2 virus life cycle, watch it here.

 

We are looking for you!

We are looking for someone with affinity for social media, who is willing to contribute in keeping track of the Twitter and LinkedIn accounts of the NVK. Please contact us if you are interested, it would be of great help!

From the lab: ERC grant

We (Sven Hennig and his team) are very excited to be part of Tom Grossmann’s project of fighting colorectal cancer using peptidomimetics. Tom just received an ERC PoC grant which is accelerating the kick-off for this endeavor. Together we have identified a family of peptidomimetic agents that bind beta-catenin and inhibit its interaction with the TCF/LEF transcription factors . For the first time, it was possible to obtain a crystal structure of a synthetic molecule bound to a therapeutically very attractive site on beta-catenin. In addition, we have confirmed cellular activity of these inhibitors verifying selective inhibition of the Wnt signalling pathway (Wendt et al. Angewandte Chemie, 2021, https://doi.org/10.1002/anie.202102082). These findings provide the ideal starting point for the development of novel therapeutics for Wnt-dependent cancers, in particular for CRC. Press: https://www.eurekalert.org/news-releases/767299.

proCOLON: ERC Proof-of-Concept granted to investigate first-in-class beta-catenin inhibitors as treatment for colorectal cancer.

https://onlinelibrary.wiley.com/cms/asset/cea8b02f-4a06-4b65-a926-69b39c2048ca/anie202102082-toc-0001-m.jpg
Development of a bicyclic β-hairpin structure that binds the transcriptional coactivator β-catenin (Wendt et al. Angewandte Chemie, 2021).

Next up: NVK Young Researchers Retreat

On September 29th and 30th, 2022, we are organizing the NVK Young Researchers Retreat! Please find the preliminary program and registration details here.

All participants will present their work, both PhD students and early researchers working in industry or industry are welcome to contribute, which will result in a wonderful and inspiring program! Our key-note speaker, Dr. Yesid A. Ramirez, will talk about his research related to . Additionally there will be plenty of time to network with our sponsors from industry, and of course with your fellow young crystallographers. Also, the career session will provide a overview of career options and plenty of time to discuss these with people who have been in the field for a longer time, both industry and academic science.

In short: interesting science, plenty of options to network, think a bit about your future career, and of course we will have a lot of fun! We hope to see you there!

Get to know the board: Loes Kroon-Batenburg

I am working in crystallography for over 40 years. I came to our lab (Laboratorium voor Kristalchemie) in 1977 as a student and worked on solving carbohydrate crystal structures with Jan Kanters. We continued this work in my PhD (1980-1985, Prof. A.F Peerdeman), when I got also interested in modelling, both with quantum chemical methods and molecular mechanics/dynamics. After my PhD, I continued working on carbohydrates and in particular on cellulose, derivatives and wood fibers with my husband Jan Kroon (then the professor of our group), with whom I did many projects financed by industry (AkzoNobel), Economic Affairs (IOP-K and EET), EU-FAIR and STW (Fig. a&b). I was a post-doc during more than 15 years (impossible these days!), but I did not mind: we were always successful in getting grants for interesting projects and I was very happy to stay with Jan in his lab. That situation changed completely when Jan died unexpectedly in 2001. Piet Gros took over the lead of the group who already transformed it into a protein crystallography lab.  I was appointed assistant professor, not without the help of the dean of chemistry, Prof. J.F.G Vliegenthart, in 2003. My research changed to methods developments in data processing, an area that I already became interested in because of my work on fiber diffraction. More recently, I became interested in diffuse scattering in both chemical and macromolecular crystallography (Fig. c). I have been active in the Diffraction Data Deposition Working Group (DDDWG) of the IUCr (International Union of Crystallography) from 2011 onward, and which now turned into a standing committee CommDat. We are setting up a new section in IUCrData: the Raw Data Letter, with the aim describing interesting, unusual, intriguing or complicated diffraction data, that could be a challenge for methods or software developers, but also for creating visibility of the data, which should be deposited in an archive with a persistent identifier (e.g. a DOI). More news on this will follow in future News Letters.

a&b) Fibre diffraction pattern of regenerated cellulose yarn (Cordenka EHM) and the crystal structure. c) Diffuse scattering in the hk0 plane of Cyclophilin A crystals.

Crystallography 50 years ago: Utrecht

The period around 1972, 50 years ago was in hindsight a time of change. Much of the research lines of the crystallography group in Utrecht had been curiosity driven and were related to research started after WW-II by Professor Bijvoet. Among his many interests were the development of the isomorphous replacement techniques for solving crystal structures and the ground breaking use of anomalous dispersion to determine the absolute configuration of chiral molecules. The first such an absolute structure determination was done by Bijvoet and his PhD students Peerdeman (his successor) and van Bommel on a rubidium salt of tartaric acid using X-ray diffraction photographic film methods. This result, that was consistent with the arbitrary choice by Fisher, was first reported in 1949 at a meeting in the USA. This led to investigations of the crystal structures of other tartrates and similar small molecules such as malonic acid and the study of hydrogen bonding. Those were light atom compounds that needed different methods to solve the phase problem as those available for heavy atom structures. This spawned local interest in and development of so called Direct Methods, in particular of a technique called Symbolic Addition that worked well for solving centro-symmetric structures. X-ray diffraction data were collected with labour intensive film techniques and later on with semi-automatic three-circle single point detector based diffractometers for which in-house data collection software was developed. Computer based calculations and software development needed for the structure determination were done initially on a Dutch made in-house ZEBRA computer, being the first one at Utrecht University. That computing facility was, when I started in 1966 as a crystallography student, already replaced by a Dutch made Electrologica X8 computer at the university computer center elsewhere in the city. The latter was an Algol60 language, one job at a time, air-conditioned large room sized system with a computing power comparable to that of an early IBM PC. During daytime, small calculation jobs with data and program supplied on paper tape were run by computer operators at the computer center. Those tapes and the output results, again often in paper tape format and line printer output, were transported twice a day by a dedicated person, who also managed the Xerox copying machine, between the lab and the computing center. Turn-around time was often one day. A correction of input errors took another day. Larger jobs such as least-squares refinement were done mainly once a week during a 6 PM to 8 AM night shift where our crystallography group had the university computer for ourselves. Many users of the computer acted both as researcher, programmer and operator doing their calculations in turn. Coming back to the lab in the morning there was always coffee ready, provided by the housekeeping ladies to keep us awake that day. All that changed within a short period 50 years ago. The crystallography lab was housed in a free standing stately city house, also known as the ‘Crystal Palace’.  The building was until the retirement of Bijvoet in 1962 in part laboratory and in part the house of the Bijvoet family. The lab moved in 1973 to a new building in the new University campus outside of the city. The computer center had moved by that time also to that campus area (de Uithof). A new multi-user American state-of-the-art Control Data computer system running Fortran had replaced the single user X8 by then. Paper tape supplied data and software were suddenly old-fashioned and practically unusable. The new standard was now IBM punch cards. All local software that was developed and used for years suddenly became obsolete and was replaced by an also American Fortran based crystallographic software package named XRAY72. Calculation jobs were now carried out in batch mode and could be submitted with an in-house terminal/lineprinter input/output station connected to the computer center. Small jobs could even be run interactively in time sharing mode. The group had now also obtained a new CAD4 diffractometer that potentially allowed for the collection of diffraction data for in the order of 25 structure studies per year. Structure determinations that took multiple months could now be completed within several weeks. One of the bottlenecks of a successful structure determination, the solution of the phase problem, was now also addressed significantly with the availability of the Direct Methods program MULTAN.  Part of the research became also more collaborative, in particular with metal-organic and coordination chemistry groups. Research shifted in the direction of intermolecular interactions, structure prediction and probability based theory  aiming to improve the success of the Direct Methods. It was interesting to be part of all those developments that allows us today, when pushed, to have in a routine case a structure report ready within a day starting with a good crystal. Unfortunately, much of the details of the procedures used will be hidden in black box software for the current crystal structure analist.

Written by Ton Spek