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How the bacterial protective shell is adapted to challenging environments

Illustration JACS Publication Cavalab[2016-07-07] Researchers at Umeå University in Sweden have published new findings on the adaptation of the bacterial cell wall in the Journal of the American Chemical Society. The study reveals novel bacterial defence mechanisms against the immune system and how they can become resistant to antibiotics.

Bacteria are surrounded by a mesh-like structure which, similar to an external skeleton, defines the cell shape and provides protection against external attacks. This remarkable polymer cell wall called peptidoglycan, given its basic composition of sugars and amino acids, is well known for being a major target of beta-lactam antibiotics such as Penicillin.

Despite this structure having been the focus of extensive investigations on the long-lasting battle against bacterial pathogens (i.e. bacteria that cause infectious diseases), there is currently little understanding of its natural variability and the consequences of such changes on the ability of bacteria to adapt and survive in a threatening environment.

Read more: How the bacterial protective shell is adapted to challenging environments

Gene amplification – the fast track to infection

Wang et al Science[2016-06-30] Researchers at Umeå University are first to discover that bacteria can multiply disease-inducing genes which are needed to rapidly cause infection. The results were published in Science on 30 June 2016.

More than 22 years ago, researchers at Umeå University were first to discover an infection strategy of human pathogenic Yersinia bacteria – a protein structure in bacterial cell-walls that resembled a syringe. The structure, named “Type III secretion system” or T3SS, makes it possible to transfer bacterial proteins into the host cell and destroy its metabolism.

After the discovery, researchers have found T3SS in several other bacteria species and T3SS has proven to be a common infection mechanism that pathogens, i.e. an infectious agent such as a virus or bacterium, use to destroy host cells. Now, Umeå researchers are again first to find a link between infection and rapid production of the essential proteins needed to form “the poisonous syringe”.

Read more: Gene amplification – the fast track to infection

“Limited only by the Imagination” - Emmanuelle Charpentier awarded the Tang Prize 2016

Tang Prize Logo[2016-06-20] The 2016’s Tang Prize in Biopharmaceutical Science recognizes Emmanuelle Charpentier together with Jennifer Doudna and Feng Zhang “for the development of CRISPR/Cas9 as a breakthrough genome editing platform that promises to revolutionize biomedical research and disease treatment”.

Dr. Charpentier’s research focuses on mechanisms of regulation in infection and immunity. Her laboratory strives to understand how RNA and protein molecules work together to control gene expression and biological processes in bacterial pathogens. To identify new molecules and decipher their origins, functions and modes of action at the molecular and cellular level, Dr. Charpentier applies a combination of a wide range of methods, including -omics, genetics, molecular biology, biochemistry, physiology as well as cell infection approaches.

Read more: “Limited only by the Imagination” - Emmanuelle Charpentier awarded the Tang Prize 2016

Cpf1: CRISPR-enzyme scissors cutting both RNA and DNA

[2016-04-20] Scientists delineate molecular details of a new bacterial CRISPR-Cpf1 system and open possible avenue for alternative gene editing uses like targeting several genes in parallel. (Nature 20 April 2016)

Only a few years after its discovery, it is difficult to conceive of genetics without the CRISPR-Cas9 enzyme scissors, which allow for a very simple, versatile and reliable modification of DNA of various organisms. Since its discovery, scientists throughout the world have been working on ways of further improving or adjusting the CRISPR-Cas9 system to their specific needs. Researchers from the Max Planck Institute for Infection Biology in Berlin, the Umeå University in Sweden and the Helmholtz Centre for Infection Research in Braunschweig have now discovered a feature of the CRISPR-associated protein Cpf1 that has previously not been observed in this family of enzymes: Cpf1 exhibits dual, RNA and DNA, cleavage activity. In contrast to CRISPR-Cas9, Cpf1 is able to process the pre-crRNA on its own, and then using the processed RNA to specifically target and cut DNA. Not requiring a host derived RNase and the tracrRNA makes this the most minimalistic CRISPR immune system known to date. The mechanism of combining two separate catalytic moieties in one allows for possible new avenues for sequence specific genome engineering, most importantly facilitation of targeting multiple sites at once, the so-called multiplexing.

Read more: Cpf1: CRISPR-enzyme scissors cutting both RNA and DNA

Nelson Gekara awarded Fernström Prize 2016

Nelson Gekara photo by Mattias Pettersson lr[2016-06-08] The Fernström Committee at the Faculty of Medicine has awarded the Erik K. Fernström prize for 2016 to Nelson Gekara, Group Leader at MIMS and the Department of Molecular Biology. Gekara’s research focuses on the regulation of the innate immune system and the connection to infection and DNA damage.

Since 2010, Nelson Gekara has been Group leader at MIMS in Umeå. He has worked with several model organisms to study how microbes interact with their host and how innate immune responses are generated and regulated.

Nelson Gekara’s team recently demonstrated the importance of DNA damage in the innate immune system. Further they have identified new signalling molecules that control the innate immune system and are involved in the protection against responses from inflammatory diseases, such as rheumatism.

Read more: Nelson Gekara awarded Fernström Prize 2016

Postdoctoral Research Opportunities in Infection Biology and Molecular Infection Medicine available at MIMS and UCMR !

Up to nine positions are open for postdoctoral candidates interested to do research in the highly interactive and multidisciplinary research environment UCMR – Umeå Centre for Microbial Research at Umeå University, Sweden.
We aim to recruit new postdoctoral scientists with competence and ideas that will strengthen the research environment and contribute to its renewal.

The programme is open to all nationalities and features of the positions include:
• Development of a project proposal forms the basis for recruitment
• Funding for research within a multidisciplinary environment
• Two years of secure funding
• Access to UCMR-MIMS-affiliated core facilities and technical platforms.
The positions are full-time for 24 months.

Read the complete announcement (deadline for registration: 15 August 2016)

Targeting metals to fight pathogenic bacteria

Akbar Espaillat Felipe CavaFelipe Cava and Akbar Espaillat at the MIMS participated in the discovery of a unique system of acquisition of essential metals in the pathogenic bacterium Staphylococcus aureus. This research was led by scientists at the CEA in France, in collaboration with researchers at the University of Pau, the INRA and the CNRS. It represents a new potential target for the design of antibiotics. These results are being published in the journal Science on Friday 27th May.

Metals are necessary for life and pathogenic bacteria have developed elaborate systems to compensate for the low concentration of these essential metals in their environment, in particular within a host. The case of iron is particularly well documented with, in some bacteria, the production of molecules called siderophores that specifically capture iron in the medium. Researchers have now identified a new metal scavenging molecule produced in the bacterium Staphylococcus aureus and baptized it staphylopine.

Read more: Targeting metals to fight pathogenic bacteria

"The quiet revolutionary" - Emmanuelle Charpentier in Nature Feature

160428 Nature Feature EC[2016-04-27] Nature’s senior European correspondent Alison Abbott visited the Max-Planck-director and UCMR guest professor in her new office in Berlin and talked to her about how the CRISPR findings changed her life. Emmanuelle  Charpentier speaks also about her life before CRISPR-Cas9 and how her lab performed the first key experiments in Austria and Sweden. Statements from former colleagues, supervisors, collaborators and co-funders complete the nice portrait of a scientist who "always seems to be moving while keeping science on the go".

play Read the News Feature in Nature 522 (28 April 2016)

Cpf1: CRISPR-enzyme scissors cutting both RNA and DNA

[2016-04-20] Scientists delineate molecular details of a new bacterial CRISPR-Cpf1 system and open possible avenue for alternative gene editing uses like targeting several genes in parallel. (Nature 20 April 2016)

Only a few years after its discovery, it is difficult to conceive of genetics without the CRISPR-Cas9 enzyme scissors, which allow for a very simple, versatile and reliable modification of DNA of various organisms. Since its discovery, scientists throughout the world have been working on ways of further improving or adjusting the CRISPR-Cas9 system to their specific needs. Researchers from the Max Planck Institute for Infection Biology in Berlin, the Umeå University in Sweden and the Helmholtz Centre for Infection Research in Braunschweig have now discovered a feature of the CRISPR-associated protein Cpf1 that has previously not been observed in this family of enzymes: Cpf1 exhibits dual, RNA and DNA, cleavage activity. In contrast to CRISPR-Cas9, Cpf1 is able to process the pre-crRNA on its own, and then using the processed RNA to specifically target and cut DNA. Not requiring a host derived RNase and the tracrRNA makes this the most minimalistic CRISPR immune system known to date. The mechanism of combining two separate catalytic moieties in one allows for possible new avenues for sequence specific genome engineering, most importantly facilitation of targeting multiple sites at once, the so-called multiplexing.

Read more: Cpf1: CRISPR-enzyme scissors cutting both RNA and DNA

Battling antibiotic resistance

movie by Knut and Alice Wallenberg Foundation, with participation of scientists from MIMS and UCMR:
Or watch the original movie on:
https://kaw.wallenberg.org/

Research about infectious diseases:

Oliver Billker in movie of Knut and Alice Wallenberg Foundation:
Or watch the original movie on:
https://kaw.wallenberg.org/

footer all slides 2014-02-06


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