New publication with Vasili Hauryliuk on "Make it or break it: how bacteria balance production and degradation of the ´magic spot´ signaling alarmone"

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).

Read more: New publication with Vasili Hauryliuk on "Make it or break it: how bacteria balance production and...

MIMS Clinical Research Fellowships awarded to two virologists

Molecular Infection Medicine Sweden (MIMS) has this week announced the annual winners of its national Clinical Research Fellowship (CRF) program. An international panel of clinical researchers has awarded fellowships to Sara Gredmark Russ at the Karolinska Institute and Anne-Marie Fors Connolly at Umeå University to conduct research into how different viruses infect human cells and cause disease.

Sara Gredmark Russ is a specialist doctor in infectious diseases at Stockholm’s Karolinska University Hospital. Following her medical degree and PhD in experimental medicine at the Karolinska Institute, she conducted research at the Whithead Institute at MIT (USA), before she established her own research group within the area of immunology, focusing on how viruses interact with the human immune system. Dr. Gredmark Russ studies tick-borne encephalitis (TBE), a serious viral infection of the central nervous system caused by tick-borne encephalitis virus (TBEV). Her team will now answer how the virus causes disease. In her fellowship project, she will work with MIMS scientist Anna Överby Wernstedt to identify human host cell factors important for TBE virus infection and replication. Her ultimate aim is to discover novel therapeutic targets to treat TBE, which are urgently required. 

Anne-Marie Fors Connolly is a clinician researcher at the Department of Clinical Microbiology and University Hospital of Umeå. Originally from Denmark, Anne-Marie Fors Connolly earned a PhD from Karolinska Institute in Stockholm, before she completed her medical degree in Umeå. She will establish a translational research group to understand the disease caused by Puumala Orthohantavirus, hemorrhagic fever with renal syndrome (HFRS), known in Sweden as “sorkfeber”. Compared to other hantavirus infections, HFRS is rarely lethal, but Dr. Fors Conolly has previously shown that it is a risk factor, for instance for heart attack and stroke. There are no drugs to eliminate the virus, and the aim now is to identify treatment strategies, which may also point the way for treating other viral hemorrhagic fevers. 

Read more: MIMS Clinical Research Fellowships awarded to two virologists

Vasili Hauryliuk (MIMS) and Gemma Atkinson (UCMR) lead milestone paper in PNAS on new kind of regulatory toxin-antitoxin system

Bacteria use small molecules to slam the brakes on their own growth

An international research team under the lead of scientists at Molecular Infection Medicine Sweden (MIMS) and the Umeå Center for Microbial Research (UCMR) have uncovered a new kind of regulatory system of toxin and antitoxin proteins in bacteria that could be a defense system against viral attack. The bioinformatic identification of the proteins and their experimental validation are now published in the high impact journal Proceedings of the National Academy of Sciences of the US (PNAS, 28 April 2020, entitled "A widespread toxin-antitoxin system exploiting growth control via alarmone signaling").

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.

Read more: Vasili Hauryliuk (MIMS) and Gemma Atkinson (UCMR) lead milestone paper in PNAS on new kind of...

New work from the Cava group provides novel insights into the genetics and physiology behind the peptidoglycan-recycling pathway

Most bacteria are surrounded by a protective cell wall consisting of a strong yet elastic polymer called peptidoglycan. The peptidoglycan cell wall is an essential structure for bacteria and thus, its biosynthesis and remodeling have always been in the spotlight when it comes to the development of antibiotics.

During bacterial growth, large amount of peptidoglycan fragments (also known as muropeptides) are released to the extracellular environment where they play roles in bacteria-bacteria and bacteria-host communication. However, in many species these fragments are predominantly re-internalized and recycled, a cellular process whose biological meaning has been elusive until now. 
Felipe Cava's research group at the Molecular Infection Medicine Sweden (MIMS) studied the genetics and physiology behind the peptidoglycan-recycling pathway using as experimental model the causative agent of cholera, Vibrio cholerae. The study was performed in collaboration with Tobias Dörr (Cornell University, USA) and Matthew K. Waldor (Harvard Medical School, USA) and the results have been published in the journal Cell Reports on 28th April.
The scientists have revealed an unnoticed link between PG recycling and synthesis to promote optimal cell wall assembly and composition.

Read more: New work from the Cava group provides novel insights into the genetics and physiology behind the...

Congratulations to Nordic EMBL Partnership for awarded NordForsk funding!

Grant awarded as part of Nordic Research Infrastructure Hubs call

The Nordic EMBL Partnership for Molecular Medicine, in which MIMS serves as the Swedish node, has been awarded 2.5 million NOK by NordForsk as part of their ‘Nordic Research Infrastructure Hubs’ initiative. The decision came after review by an international expert panel, who rated the Nordic EMBL Partnership’s application as “outstanding”.

Today, the Partnership serves as an exchange platform for students, postdocs, group leaders and support personnel to transform their working environments and career development. The current hub program will further realise this potential.

Read more: Congratulations to Nordic EMBL Partnership for awarded NordForsk funding!