Dear Colleagues, when writing a new Editorial, it is quite peculiar to go back and browse the last CIISB Newsletter, published at the beginning of February 2020.

www.ciisb.org  |  2/2020
Sent 6 Aug 2020, 11:03

Newsletter

Editorial

Dear Colleagues,

when writing a new Editorial, it is quite peculiar to go back and browse the last CIISB Newsletter, published at the beginning of February 2020. Looking at the number of upcoming activities and meetings advertised for spring and summer 2020, and recapitulating now, six months later, what has actually happened, it looks that the world has turned upside-down and teared apart everything what we planned. But not our world is to blame. 

Only a tiny beast SARS-CoV-2, and its associated disease COVID-19, took temporarily control of our lives and everyday activities. And we, humans, allowed it. Life has changed, but not forever. Science will find a cure. Yet, the Covid pandemic gave us a lesson. Let’s take it as an opportunity to change what has to be changed to make our planet and our lives safer.

Many science related activities stopped across the globe and many research institutions shut down their labs. Fortunately, it was not the case of the CIISB hosting institutions BIOCEV and CEITEC. Although we had to restrict direct access for external users for a number of weeks, remote access for all users continued and remained uninterrupted. All possible measures have been adopted to keep our personal save and fully functional. In order to assist research helping to cope with the Covid pandemic, CIISB offered priority access to groups that needed to use CIISB structural biology services for projects directly related to studies of the virus and projects aiming to develop an effective vaccine or treatment. For successfully accepted proposals no financial contribution is requested for the measurement/service. There are currently five projects with the Covid topic. One of them has been already successfully finished and its results published in one of the top journals, Nature Communications. The results of Evžen Bouřa and Radim Nencka research groups from the Institute of Organic Chemistry and Biochemistry, Czech Academy of Science, Prague, are presented in the section Research Highlights below.

Despite the pandemic, the access to CIISB core facilities remained at the level comparable to previous years and number of reviewed and accepted proposals surpassed our expectations. Compared to the whole year 2019 with 232 project proposals, CIISB registers 195 access applications as of July 31, 2020. During the period January - July 2020, results obtained with the CIISB assistance were published in 53 peer-reviewed papers recorded by Web of Science, most of them in journals with high impact factors, including two papers in Nature Communications and other two in the Journal of the American Chemical Society. Two research highlights from Nature Communications and five selected publications from leading journals are listed below. All of them can be found on our web at the Research Highlights Archive and in the section Publications.

The project UP CIISB of the OP VVV Call 02-18-046 Research Infrastructures II for the period 2020-2022 started successfully in January 2020 and the first acquisitions of new instrumentation have already been installed and put in operation in CFs Proteomics and Cryo-electron Microscopy and Tomography. More details are presented in the sections News.

Training and workshops postponed in spring and summer are slowly appearing in calendar for autumn and winter. The first activities are listed in the section Save the date below and in Events on the CIISB web. I am sure that others will follow soon. Please, check the section Events on our web frequently to stay up-to date.

In the attempt to enhance the information content of our web and to emphasize the ongoing efforts to cope with the Covid pandemic, new section “Research Highlights of Coronavirus Structural Studies” has been added. We will highly appreciate if you point out any paper which you consider important to be presented on our web by sending a mail to readerscorner@ciisb.org

Despite all troubles connected with the current situation I wish you enjoyable summer and fall and endless energy to cope with Covid pandemic.

Vladimír Sklenář

News

COVID-19 measures at CIISB

All CIISB Core facilities are fully functional. Visits of external foreign users are regulated by the Measures concerning foreigners and border crossing of the Czech Government. Please, check the current status on the web and contact the staff for details.

CIISB offers priority access to groups that need to use CIISB structural biology services for projects directly related to studies of the virus and projects aiming to develop an effective vaccine or treatment. To request priority access, please submit a research proposal with „COVID-19“ in the title of the proposal, through the online application system HERE. Successfully accepted proposals will be free of charge, and no financial contribution will be requested for the measurement/service.

Upgrade of the workflow for cryo-electron tomography and microscopy

The CIISB Cryo-electron microscopy core facility at CEITEC Masaryk University is expanding its services in the sample preparation for electron microscopy. The facility has recently acquired high-pressure freezer Leica EM ICE for vitrification of bulky biological specimen (up to 200 mm thickness). In addition, the freeze-substitution unit Leica EM AFS2 for resin embedding of the high-pressure frozen samples and the ultramicrotom Leica EM UC7 with the adapter for cryo-ultramicrotomy were purchased in order to provide the facility users with the complete workflow for preparation of thin section samples for both room-temperature electron microscopy and cryo-electron microscopy.

Job opportunity - research scientist for the Centre of Molecular Structure, Biophysical methods facility

The Institute of Biotechnology of the Czech Academy of Sciences at BIOCEV Centre is looking for a research scientist with a significant experience in application of biophysical techniques and/or spectroscopic techniques.

New timsTOF Pro Mass Spectrometer installed at CEITEC

New timsTOF Pro Mass Spectrometer (Bruker) has been installed at the Proteomics Core Facility, CEITEC MU. The new instrument brings another separation dimension (according collisional cross sections) in qualitative and quantitative characterization of complex protein samples as it is equipped by trapped ion mobility spectrometry (TIMS) module.

Dual TIMS technology and PASEF (Parallel Accumulation Serial Fragmentation) acquisition method provide almost 100% duty cycle and up to 100 Hz acquisition speed without compromising sensitivity and mass resolution. It opens us a way to deeper insights in proteome even in case of low amounts of samples.

New section at CIISB website - Highlights of Coronavirus Structural Studies

The CIISB website introduced a new section entitled „Highlights of Coronavirus Structural Studies“. This section presents the latest and most important results of structural studies of SARS-CoV-2 and its constituents. Its content will be updated regularly. 

CIISB Access

Applications January - July 2020

  • 122 internal applications
  • 63 external applications
  • 10 applications from foreign users

Applications overview in total

  2016 2017 2018 2019 01-07/2020
CIISB Internal users 123 178 177 147 122
CIISB External users (Czech) 35 50 51 58 63
CIISB External users (foreign) 5 14 15 27 10

 

Save the date

(Bio) Atomic Force Microscopy (bioAFM) Basic Course

1 October 2020, 8:45 AM

CEITEC Masaryk University Brno, Building A35, Seminar room 211

Hands-on workshop organised by Nanobio Core Facility and Measurement Technic Moravia.

The workshop will offer lectures on basics of atomic force microscopy, sample preparation and data processing and also a lab tour connected with short hands-on session.

The workshop will be streamed online. It is possible to register only for online attendance.

Advanced methods in macromolecular crystallization IX

12 – 17 October 2020
Nové Hrady, Czech Republic

The course (for undergraduate, postgraduate students and postdocs with an interest in macromolecular crystallization) is a continuation of eight previous successful FEBS-supported crystallization courses. The main aim and big advantage of this course compared to other established protein crystallization courses is consideration of theoretical aspects of crystal growth process as well as practical work: there will be a healthy mix of advanced discussions of the theory and of laboratory experiments and the possibility for participants to crystallize their own proteins. Direct contact between participants and experts in the field acting as teachers and tutors ensures the possibility of discussing and solving a participant's own scientific problems.

This course, originally planned for May 2020, is postponed to October 2020.

The registration deadline is currently extended until August 10, 2020.

 

Research highlights

the best of science obtained using CIISB Core Facilities

Nature Communication

Evžen Bouřa and Radim Nencka Research Groups

COVID-19 pandemic is caused by the SARS-CoV-2 virus that has several enzymes that could be targeted by antivirals including a 2'-O RNA methyltransferase (MTase) that is involved in the viral RNA cap formation; an essential process for RNA stability. This MTase is composed of two nonstructural proteins, the nsp16 catalytic subunit and the activating nsp10 protein. We have solved the crystal structure of the nsp10-nsp16 complex bound to the pan-MTase inhibitor sinefungin in the active site. Based on the structural data we built a model of the MTase in complex with RNA that illustrates the catalytic reaction. A structural comparison to the Zika MTase revealed low conservation of the catalytic site between these two RNA viruses suggesting preparation of inhibitors targeting both these viruses will be very difficult. Together, our data will provide the information needed for structure-based drug design.

Krafčíková, P., Šilhan, J., Nencka, R., and Bouřa, E.: Structural analysis of the SARS-CoV-2 methyltransferase complex involved in coronaviral RNA cap creation, Nat. Commun. (2020) 11, 3717, https://doi.org/10.1038/s41467-020-17495-9

Nature Communication

Pavel Plevka Research Group

Alphaproteobacteria, which are the most abundant microorganisms of temperate oceans, produce phage-like particles called gene transfer agents (GTAs) that mediate lateral gene exchange. However, the mechanism by which GTAs deliver DNA into cells is unknown. Here we present the structure of the GTA of Rhodobacter capsulatus (RcGTA) and describe the conformational changes required for its DNA ejection. The structure of RcGTA resembles that of a tailed phage, but it has an oblate head shortened in the direction of the tail axis, which limits its packaging capacity to less than 4,500 base pairs of linear double-stranded DNA. The tail channel of RcGTA contains a trimer of proteins that possess features of both tape measure proteins of long-tailed phages from the family Siphoviridae and tail needle proteins of short-tailed phages from the family Podoviridae. The opening of a constriction within the RcGTA baseplate enables the ejection of DNA into bacterial periplasm.

Bárdy,P., Füzik, T., Hrebík, D., Pantůček, R., Beatty, T.J. and Plevka, P: Structure and mechanism of DNA delivery of a gene transfer agent, Nat. Commun. (2020) 11, 3034.doi.org/10.1038/s41467-020-16669-9

Selected publications

V. Henrichs, et al.: Mitochondria-adaptor TRAK1 promotes kinesin-1 driven transport in crowded environments, Nature Communications, 11 (2020) 13, 10.1038/s41467-020-16972-5 

G. Kalnins, et al.: Encapsulation mechanisms and structural studies of GRM2 bacterial microcompartment particles, Nature Communications, 11 (2020) 13, 10.1038/s41467-019-14205-y 

L. Steiningerova, et al.: Different Reaction Specificities of F420H2-Dependent Reductases Facilitate Pyrrolobenzodiazepines and Lincomycin To Fit Their Biological Targets, Journal of the American Chemical Society, 142 (2020) 3440-3448, 10.1021/jacs.9b11234 

P. Vojackova, et al.: Stereocontrolled Synthesis of (-)-Bactobolin A, Journal of the American Chemical Society, 142 (2020) 7306-7311, 10.1021/jacs.0c01554 

A. Styskalik, et al.: Mildly acidic aluminosilicate catalysts for stable performance in ethanol dehydration, Appl. Catal. B-Environ., 271 (2020) 11, 10.1016/j.apcatb.2020.118926 

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Masaryk University