Make it or break it: how bacteria balance production and degradation of the ‘magic spot’ signaling alarmone
[2020-05-11] When stressed or starved, bacteria regulate their metabolism by producing signalling molecules called alarmones or ‘magic spots’. In the majority of bacteria, the magic spot compounds are both made and destroyed by a large, complex enzyme called Rel. The question of how Rel switches from making the alarmone to degrading it was finally resolved by an international team from Sweden – Vasili Hauryliuk (MIMS & UCMR) – and Belgium: Jelle Hendrix (Hasselt University) and Abel Garcia-Pino (Université Libre de Bruxelles). The results of this study were published in the high impact journal Nature Chemical Biology ("A nucleotide-switch mechanism mediates opposing catalytic activities of Rel enzymes", 11 May 2020).
The team have studied a Rel enzyme from a thermophilic bacterium Thermusthermophilus using a combination of structural (X-ray), biochemical (enzymology) and biophysical (single molecule FRET assays and Isothermal Titration Calorimetry). Since the T.thermophilus has an optimal growth temperature of about 65 °C, by solving the structures at room temperature the researchers could slow down the enzyme enough to ‘catch’ it in the act of synthesising or degrading the alarmone. It turned out that binding of the substrates to the active site region (domain) that is responsible for synthesis of the ‘magic spot’ allosterically inhibits the domain responsible for its degradation – and vice versa, binding of the substrates to the degradation domain inhibits the synthesis domain. This simple but elegant mechanism ensures that bacteria avoid wasteful production and degradation of the magic spot signalling molecule. Biochemical characterisation of T.thermophilus was performed in Umeå by Dr. Hiraku Takada who is supported by a personal postdoctoral fellowship from the Umeå Centre for Microbial Research (UCMR).
When bacteria get stressed e.g. through antibiotic treatment or the lack of nutrients, they slow down their growth mechanism by small signaling molecules called Alarmones. The Atkinson and Hauryliuk labs at Umeå University have worked on the proteins that make and degrade alarmones for over a decade. They previously revealed the ubiquitous presence of small proteins that make alarmones, called small alarmone synthetases or SASs, encoded in bacterial genomes.
It was an unanswered question why bacteria carry SAS proteins in addition to their standard tool-set for alarmone synthesis and degradation. Now, Gemma C. Atkinson, Vasili Hauryliuk and their colleagues found an explanation. They showed that some SASs are components of so-called toxin-antitoxin (TA) systems.
Toxin-antitoxins genes are enigmatic components of microbial genomes. What toxins of TA systems all have in common is that they slam the brakes on growth and reproduction. This is counteracted by their antitoxins which are encoded by adjacent genes. Antitoxins can also work in different ways, either binding to the toxin to stop its action, or counteracting the effect of the toxin in an indirect way.
Immune testing for Coronavirus created by researchers in Västerbotten
[2020-04-15] Researchers at Umeå University and Norrland University Hospital have developed an antibody test for the new Corona virus
People who were once infected with the coronavirus also become immune to re-infection. By using tests that measure whether the body's immune system has reacted to the coronavirus, it is possible to identify people who are resistant to the infection. This is of particular importance for staff working in healthcare or working with risk groups, but also to determine so-called flock immunity, when enough people are immune to the spread of the virus.
On initiative of University Lecturer Mattias Forsell and through collaboration between researchers at Umeå University and the University Hospital in Umeå, a test has been developed in a short time, which could show immunity to coronavirus.
UCMR - a “jewel in the crown” of the Linnaeus Centres of Excellence in Sweden
The evaluation panel placed UCMR at the top in all categories
[2020-03-05] “Yes, do it again!”, was the short answer of Jürgen Mlynek, professor at Humboldt Universität zu Berlin, on the question if the Linnaeus Programme has been successful. The evaluation of the 40 Centres of Excellence (CoE) within the Linnaeus Programme was presented and discussed at the Swedish Centre of Excellence Investments Conference last Wednesday in Stockholm. The programme was set up by Swedish Research Council (VR) and the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS) after a governmental decision in 2005 and provided 10-years funding to each CoE.
The international Expert Panel, chaired by Jürgen Mlynek, and co-chaired by Marja Makarow, professor and director at the Biocenter in Helsinki, Finland, focused on three areas: Research performance, societal relevance and international competitiveness. UCMR was in all three areas ranked as one of the top three centres, as highlighted by Mlynek and Makarow during the conference.
“Build on what was already strong”
In its report, the reviewers especially mentioned the strategy of the UCMR leadership, namely the “distinguished first Director of UCMR”, professor Bernt Eric Uhlin, who had the aim “to build on what was already strong and then hire the best people”. UCMR was early out to develop model systems to identify new control strategies to combat antimicrobial resistance. The evaluation panel was so impressed by the centre’s research performance that it judged it as “one of the jewels in the crown” of the Linnaeus Centres.
“We are indeed very pleased with the panel´s rating of UCMR as a Centre of Excellence with top qualities. This gives us strong encouragement for the continued development of a vivid and strong research environment among UCMR researchers”, commented Bernt Eric Uhlin
The panel also was asked to identify the top three universities that can serve as good examples for both hosting CoE´s but also for using the investment to further their international competitiveness. Here, Umeå University was ranked among the top three universities, based on criteria which addressed organization, management, knowledge transfer, collaboration and communication, and added value of the CoE.
Umeå Centre for Microbial Research (UCMR) was awarded a Linnaeus Grant of 90 million SEK for the period of 2008-2018 from the Swedish Research Council. Initially, a consortium of 16 UCMR principle investigators stood behind an application that was strongly endorsed by the university’s vice-chancellor at that time, Göran Sandberg. UCMR was formed 2004-2005 as a bottom-up initiative with the vision to establish a world-leading and sustainable science environment promoting cutting-edge biomedical research in molecular infection medicine at Umeå University. It included a multi-disciplinary group of research faculty from both the faculty of medicine and the faculty for science and technology. A large number of additional researchers became affiliated to UCMR over the years and by 2019 the UCMR network consisted of more than 80 principle investigators and their research groups.
The UCMR research environment was the basis for establishment of MIMS
Thanks to the UCMR, many excellent scientists were internationally recruited to different departments with life science research in Umeå. And the establishment of The Laboratory for Molecular Infection Medicine Sweden (MIMS) was entirely based on UCMR and its aim towards a world-leading and sustainable science environment in molecular infection medicine. At the onset of MIMS was also the successful recruitment of Emmanuelle Charpentier who did her seminal work on the gene editing tool CRISPR-Cas9 during her time at MIMS and UCMR.
Congratulations! Swedish Research Council Funding to UCMR/MIMS Scientists!
[2019-10-25] Congratulations to six UCMR/MIMS PIs, who will receive funding from the Swedish Research Council!
Within the funding areas Medicine and Health, the Vetenskapsrådet granted SEK 71,9 Million to Umeå University. More than 36% of the funding to Umeå will UCMR /MIMS PIs receive for the following projects:
Niklas Arnberg, SEK 7.6 million for his project "Viral gastroenteritis: Models, molecules and mechanisms" (funding period 2020-2023)
Gemma Atkinson, SEK 3.6 million for her project "Molecular evolution, epidemiology and mechanism of ABCF-mediated antibiotic resistance" (funding period 2020-2022)
Jonas Barandun, SEK 6.6 million starting grant for his project "A molecular movie of ribosome biogenesis in Mycobacteria" (funding period 2020-2023)
Anders Hofer, SEK 2.4 million for his project "Drug development against human pathogens, which are dependent on nucleotides from the host organism" (pfunding period 2020-2022)
Vicky Shingler, SEK 3.6 million for her project "Control and disarming of the Type VI Nano Machine" (funding period 2020-2022)
Bernt Eric Uhlin, SEK 3.6 million for his project "Bacterial fitness mechanisms of the versatile pathogenic variants of Escherichia coli and the emerging opportunistic pathogen Acinetobacter baumannii" (funding period 2020-2022)
In total the Swedish Research council funded 254 projects with in total almost SEK 1.1 billion.