Fighting against multi-resistant bacteria
In their search for new therapeutic strategies, Würzburg research groups employ modern digital technologies. The Free State of Bavaria provides millions for this purpose.
Developing fundamentally new approaches against multi-resistant germs: This is the goal of the new Bavarian research network bayresq.net. The Free State of Bavaria is providing over ten million euros for this purpose. Research groups from the Julius-Maximilians-Universität (JMU) Würzburg are involved in two of the six funded projects. They will receive around 2.7 million euros over the next five years.
Using digital methods for designing RNA antibiotics
Conventional antibiotics are usually effective against a broad spectrum of bacteria. As effective as they may be, they unfortunately also promote the development of multi-resistant germs. They also destroy the protective microbiota – including bacteria that have useful effects in the human intestine.
Using an interdisciplinary approach, a JMU team led by Professor Jörg Vogel, junior Professor Lars Barquist and junior research group leader Dr. Franziska Faber will investigate new antibiotics that can be used to treat specific types of bacteria. In principle, such novel antibiotics based on the nucleic acid RNA can be "programmed" according to simple chemical principles and can also be reprogrammed if resistance occurs.
"Digitalisation has arrived in the life sciences since quite a while ago and the problem of antibiotic resistance must be tackeled/approached from different angles," says Jörg Vogel. "The funding provided by bayresq.net will allow us to develop digital strategies to combat multi-resistant germs that go hand in hand with our work in the laboratory".
The aim of the project at the JMU Institute of Molecular Infection Biology / Research Center for Infectious Diseases (IMIB / ZINF) is to develop universal rules for programming effective antibiotics and to decipher the underlying mechanisms. For this purpose, the team uses a combination of high-throughput sequencing and machine learning. The aim is to create a very powerful digital platform for the future application of RNA-based antibiotics against a variety of bacteria.
Salmonella and Campylobacter under pressure
Pathogens are exposed to diverse chemical stimuli and stress conditions during the infection process. These stimuli originate from the host organism, the microbiota and food, as well as from antibiotics and other drugs. Pathogens have various survival and adaptation strategies to adapt to these changing conditions. However the molecular mechanism of how a given stimuli activates particular adaptation responses is largely unknown.
This is where the StressRegNet consortium comes in, which is led by Professor Cynthia Sharma from the IMIB / ZINF and junior research group leader Dr. Ana Rita Brochado from the ZINF / Biocenter together with Professor Christian Müller from the Institute of Statistics of the Ludwig-Maximilians-Universität Munich. The team will investigate different chemical stimuli and regulatory signaling pathways that control host adaptation of Salmonella and Campylobacter. Both are two widespread food-borne pathogens that have recently been classified by the World Health Organization (WHO) with high priority for research and development of new antibiotics.
Feldberg prize awarded to Jörg Vogel
Jörg Vogel has been awardewd the 2019 Feldberg prize. The Feldberg Foundation aims to promote scientific exchange between German and British researchers and is awarded annually to a scientist from each country based on their outstanding contribution to their respective research areas.
Poster prize at the 71st Annual Conference of the German Society for Hygiene and Microbiology
Congratulations to Austin Mottola (AG Morschhäuser), who won one of the five awarded poster prizes at the recent 71st Annual Conference of the German Society for Hygiene and Microbiology (DGHM), which took place from 25-27 February 2019 in Göttingen. Austin received the award for the following poster, which was selected from a total of more than 150.
Austin Mottola, Bernardo Ramírez-Zavala, Joachim Morschhäuser: “Identification of targets of the essential protein kinase Snf1 in Candida albicans”.
Drug-induced mating competence enables Candida albicans cells to combine individually acquired resistance mechanisms
The pathogenic yeast Candida albicans can develop resistance to the widely used antifungal drug fluconazole by various mechanisms, with clinically relevant high resistance levels requiring a combination of these mechanisms. Joachim Morschhäuser’s group from IMIB now report in mBio that under selective pressure by the drug, those cells in a population that have acquired resistance mutations undergo genetic recombination events that further increase drug resistance and simultaneously make this normally asexual fungus mating-competent. Mating of resistant cells and subsequent reassortment of their combined chromosome sets generates progeny that is highly drug-resistant.
Infections by C. albicans are usually treated with fluconazole, an antifungal agent that inhibits the biosynthesis of ergosterol, the main sterol in fungal membranes. C. albicans can acquire fluconazole resistance by mutations in the target enzyme that decrease drug binding or by gain-of-function mutations in transcription factors that result in the constitutive overexpression of ergosterol biosynthesis genes and multidrug efflux pumps. Combinations of these resistance mechanisms potentiate drug resistance and are commonly found in highly fluconazole-resistant clinical isolates. Such isolates are generally homozygous for the resistance mutations, because loss of heterozygosity for a mutated allele enhances drug resistance in this diploid fungus. The group has now shown that loss of heterozygosity for resistance mutations, which can occur by mitotic recombination events or whole-chromosome loss and duplication, is frequently accompanied by homozygosity at the mating type locus (MTL). This enables the drug-resistant cells of a population to switch to the mating-competent opaque morphology and mate with each other to combine their resistance mechanisms (link to video). The tetraploid mating products then reassort their merged genomes to return to the diploid state by a non-meiotic mechanism. In this way, they can further increase their drug resistance under selective pressure by losing the wild-type alleles and retaining the advantageous mutated alleles. Therefore, fluconazole treatment not only selects for resistance mutations but also promotes genomic alterations that confer mating competence, which allows cells in an originally clonal population to exchange individually acquired resistance mechanisms and generate highly drug-resistant progeny.
Popp C, Ramírez-Zavala B, Schwanfelder S, Krüger I, Morschhäuser J (2019) Evolution of fluconazole-resistant Candida albicans strains by drug-induced mating competence and parasexual recombination. mBio 10:e02740-18. The paper has been selected as Paper of the Month by the DGHM. DGHM paper of the month
Legend to the video (avi format): Mating of C. albicans cells with different fluconazole resistance mutations (a GFP-labeled MTLa strain with a mutation in the transcription factor Mrr1 and an RFP-labeled MTLαlpha strain with a mutation in the drug target enzyme). The video shows shmoo formation by the mating-competent opaque cells, followed by cell fusion (illustrated by the mixing of the cytosolic fluorescent markers), and production of progeny cells from the zygote. Video taken by Bernardo Ramírez-Zavala.
ZINF and IMIB 25th Anniversary
The Research Centre for Infectious Diseases (ZINF) and the Institute of Molecular Infection Biology (IMIB) at the University of Würzburg celebrated their 25th Anniversary with a scientific symposium on November 14th, 2018, covering the past and future of infectious diseases research. The day also celebrated Dr. Tobias Ölschläger’s many contributions and achievements over the years upon his retirement.
The ZINF was founded in 1993 to be the first integrative centre in Germany studying infectious diseases caused by bacteria, fungi and parasites. The ZINF builds an interdisciplinary and cross-faculty network that is dedicated to the research of several infectious diseases that severely impact human health. It includes researchers from the Medical faculty, including the University Hospital, as well as Biology, Chemistry, and Pharmacy. Recently, the ZINF grew further by inclusion of new members from the recently established Helmholtz Institute for RNA-based Infection research (HIRI) and the Max-Planck-Research Groups on Systems Immunology in Würzburg. An important element of the ZINF are the independent Young Investigator groups, whose work focuses on current emerging topics in microbiology and infectious diseases.
The ZINF 25th anniversary celebrations included reflections on the achievements of the ZINF by current ZINF Spokesperson Prof. Cynthia Sharma, President of the University Prof. Alfred Forchel, the Mayoress of Würzburg Marion Schäfer Blake, Prof Tone Tonjum representing the ZINF Scientific Advisory Board and former ZINF Young Investigator Dr. Daniel Lopez as well as former ZINF spokespersons Prof. Jörg Vogel and Prof. Jörg Hacker, the president of the German National Academy of Sciences Leopoldina.
The day included a variety of scientific presentations, including Prof. Staffan Normark (Karolinska Institute) the 2018 recipient of the Robert Koch Gold medal. Current ZINF Young Investigators Sina Bartfeld, Sebastian Geibel (Bavarian Elite Network), Christian Perez (ZINF/IZKF), Franziska Faber and Ana Rita Brochado (Biocentre/ZINF) provided overviews of their groups work.
Current frontiers in infectious disease research were outlined by ZINF Scientific Advisory Board member Prof. Eric Pamer (Memorial Sloan-Kettering Cancer Center), describing the use of commensal bacterial to combat antibiotic resistant infections, Prof. Dirk Brockmann (Robert Koch Institute/Humboldt University Berlin) on digital epidemiology and network perspectives of disease dynamics and Dr. Noam Stern-Ginossar (Weizmann Institute) on how RNA modifications shape the response to viral infection.
The Symposium ended with a celebration of the career of Dr. Tobias Ölschläger, who retired during 2017. His long standing research interests on pathogenic E. coli and the use of probiotic E. coli strain Nissle to treat infections was reflected in talks by his former postdoc advisor Dr. Dennis Kopecko (Combivax) and Prof. Dirk Haller (TU Münich).
For further information:
Genome organisation and structure controls antigenic variation
How parasites modulate their surface proteins to evade recognition and elimination by the immune system remains poorly understood. Research at the ZINF by the team of Nicolai Siegel and reported in Nature, provides molecular insight into the role of genome structure and organisation in controlling antigenic variation in the parasite Trypanosoma brucei.
Pathogens that constantly encounter the mammalian immune system have developed complex strategies to avoid elimination. One strategy is to cover their surface with multiple copies of a hypervariable surface protein, the identity of which can be periodically switched, enabling them to temporally multiply undetected within the body. Despite decades of research the predominant factors that enable the mutually exclusive expression of a single surface protein and which determine the identity of the variant that is expressed after the switch in expression are currently unknown in any organism.
Nicolai Siegel, Laura Müller, Raul Cosentino and coworkers, asked if the 3-dimensional (3-D) organisation of the parasite genome could play a role in controlling the identity and expression of the surface coat protein. Using Hi-C to identify genomic loci that are in close 3-D proximity revealed that the sites from which surface coat genes could be expressed spatially clustered together in the nucleus despite being located on different chromosomes. Disruption of this higher order genome structure and increasing DNA accessibility by deletion of the histone variants H3.V and H4.V, which have previously been shown to demark transcription start and termination sites, increases switching in the expressed surface protein. Single-cell RNA-seq studies, performed in collaboration with Emmanuel Saliba at the Helmholtz Institute for RNA-based Infection Research, also revealed a loss in mutually exclusive expression as seen by the simultaneous expression of multiple variants in individual parasites. The mechanism of switching occurs via DNA recombination with the absence of histone variants leading to increased interactions between two genomic loci as well as increased DNA accessibility.
The identification of the molecular events involved in antigenic variation in Trypanosomes sheds new light on the role of genome structure and organisation and may in the future lead to new strategies for disrupting a pathogen’s ability to evade the immune system.
Laura Müller*, Raúl Cosentino*, Konrad Förstner, Julien Guizetti, Carolin Wedel, Noam Kaplan, Christian Janzen, Panagiota Arampatzi, Jörg Vogel, Sascha Steinbiss, Thomas Otto, Antoine-Emmanuel Saliba, Robert Sebra & T. Nicolai Siegel Genome organization and DNA accessibility control antigenic variation in trypanosomes. DOI: http://dx.doi.org/10.1038/s41586-018-0619-8
Cas9 also cleaves RNA
The discovery and development of the CRISPR-Cas9 system into a molecular tool that cleaves chosen DNA sequences is dramatically changing our ability to modify genomes. IMIB researchers led by Cynthia Sharma together with the lab of Chase Beisel now report in Molecular Cell that Cas9 can also cleave RNA – adding a new dimension to this flexible system for manipulating cells.
CRISPR-Cas is a bacterial adaptive immune system. DNA sequences of previous infectious agents, such as viruses, are stored within the bacterium’s genome where they function as a molecular memory of previous infections. These sequences are transcribed into RNA (called guide RNA), which associate with an endonuclease such as Cas9, this guide RNA-Cas9 complex interrogates nucleic acids within the bacterium until in finds a sequence match and therefore an indication of an ongoing infection. The RNA-Cas9 complex cleaves the recognised foreign DNA halting the infection.
Gaurav Dugar, Cynthia Sharma and coworkers from IMIB, together with the group of Chase Beisel from North Carolina State University and the Helmholtz Institute for RNA-based Infection Research (HIRI), asked if Cas9 from the food-bourne pathogen Campylobacter jejuni could also target RNA as well as DNA. Unexpectedly, Cas9 not only associates with around 100 bacterial RNAs but also cleaves them in the vicinity of specific sequences specified by its guide RNA. The authors seized upon this opportunity to show that the Cas9 complex could be guided to other RNAs by changing the sequence of its guide, providing the basis for a number of different applications to target cellular RNAs. These open new avenues for the flexible isolation of specific RNAs, RNA imaging as well as eradicating RNA viruses and even cellular RNAs to study their function.
For further information see also:
Gaurav Dugar, Ryan T. Leenay, Sara K. Eisenbart, Thorsten Bischler, Belinda U. Aul, Chase L. Beisel, Cynthia M. Sharma: CRISPR RNA-dependent binding and cleavage of endogenous RNAs by the Campylobacter jejuni Cas9; Molecular Cell, DOI: doi.org/10.1016/j.molcel.2018.01.032
How a pathogenic fungus overcomes host defenses
The yeast Candida albicans can be an opportunistic pathogen and also develop resistance to antimycotic drugs. IMIB researchers Irene Hampe and Joachim Morschhäuser report in PLoS Pathogens that the fungus becomes resistant to both drug therapy and innate host defenses by a related mechanism to establish itself in the oral cavity.
Candida albicans is normally a harmless commensal in the oral cavity and the gastrointestinal and urogenital tracts of most healthy people. Nevertheless, this fungus can also cause symptomatic infections, especially when host defenses are weakened. Although such infections are usually effectively treated with antimycotic drugs, C. albicans can develop drug resistance, particularly after long-term therapy of oral candidiasis with azole antifungals. Azole resistance is often caused by activating mutations in zinc cluster transcription factors, a family of transcriptional regulators that is specific to the fungal kingdom. Such gain-of-function mutations result in the constitutive overexpression of their target genes, including genes encoding efflux pumps that remove the drugs from fungal cells.
Irene Hampe and Joachim Morschhäuser from IMIB, together with collaborators from Buffalo/USA, investigated if C. albicans can use a similar mechanism to acquire resistance against defense molecules produced by the human host itself. They took advantage of a comprehensive library of C. albicans strains containing artificially activated forms of all its zinc cluster transcription factors, which was previously generated in the Morschhäuser lab. Using this approach, they found that a hyperactive form of a transcription factor termed Mrr1 (multidrug resistance regulator 1) conferred increased resistance to the antimicrobial peptide histatin 5, which is produced in the saliva of humans to protect the oral cavity against pathogens and acts intracellularly to kill C. albicans. Intriguingly, C. albicans strains that have acquired resistance against the azole antifungal drug fluconazole often contain mutations in Mrr1 that activate the transcription factor. The research team showed that such strains not only have acquired fluconazole resistance but also increased resistance to histatin 5, which was partially caused by Mrr1-mediated overexpression of the multidrug efflux pump MDR1. This represents an additional advantage for the fungus in the oral cavity that may compensate for the fitness costs caused by the deregulated gene expression in the absence of the drug. These findings demonstrate that antimycotic therapy can promote the evolution of strains that have simultaneously acquired increased resistance against an innate host defense mechanism and are thereby better adapted to specific host niches.
Hampe IAI, Friedman J, Edgerton M, Morschhäuser J (2017) An acquired mechanism of antifungal drug resistance simultaneously enables Candida albicans to escape from intrinsic host defenses. PLoS Pathog 13(9): e1006655. https://doi.org/10.1371/journal.ppat.1006655.
Heinz P.R. Seeliger prize for Prof. Dr. Joachim Morschhäuser
IMIB professor Joachim Morschhäuser has been awarded the Heinz P.R. Seeliger prize for his research on the pathogenic yeast Candida albicans, especially for his pioneering work on antifungal drug resistance mechanisms.
The prize is named after Prof. Dr. Seeliger, who was the Chair of the Institute for Hygiene and Microbiology of the University of Würzburg from 1965-1989. After his death in 1997, his widow, Dr. Brigitte Seeliger, established the Heinz P.R. Seeliger foundation, whose aim is to promote scientific research in the areas of listeriosis, medical mycology and enteric infections. The prize is awarded annually in turn to outstanding researchers in these fields. This year’s prize was awarded by the head of the foundation, Prof. Dr. med. Herbert Hof, at the 51st Annual Meeting of the German-speaking Mycological Society (DMykG) on 31st August, 2017, in Münster.
Parasite gene expression – where to begin?
Parasites such as Trypanosoma brucei use highly unusual strategies to regulate gene expression and despite intensive research it remains an enigma how control the initiation of transcription. New research from Carolin Wedel and ZINF Young Investigator Nicolai Siegel published in The EMBO Journal reveals a link between genome sequence, packaging and organisation in ensuring efficient gene expression.
The three evolutionary related protozoan parasites, Trypanosoma brucei, Trypanosoma cruzi and Leishmania ssp are the causative agents of human sleeping sickness, Chagas diseases and leishmaniasis, respectively, and are responsible for human deaths in large parts of the world. These highly evolutionarily diverged eukaryotes seem to use different principles of gene organisation and control to regulate gene expression. For example, in these pathogens functionally related protein-coding genes are organized in long polycistronic transcription units and primary transcripts are co-transcriptionally processed into individual mRNAs by unusual coupled trans splicing and polyadenylation reactions. Most surprisingly, unlike any eukaryote studied thus far, these protozoan parasites appear to completely lack the ability to regulate transcription and RNA pol II promoter sequence motifs have been elusive, meaning that it remains unclear how transcription is initiated.
The Siegel lab used complementary molecular and genome-wide approaches to identify the principles that define and facilitate transcription as well as modulate the local chromatin composition in T. brucei. Systematic investigation of specific DNA elements to drive transcription initiation and to modulate chromatin structure in vivo identified a GT-rich promoter motif that was able to drive unidirectional transcription and to promote the targeted deposition of the histone variant H2A.Z. In addition, high-resolution nucleosome occupancy maps generated in this study, suggest that nucleosome positioning may affect RNA maturation pointing to a previously unrecognized layer of gene regulation
New IMIB Professor
Prof. Cynthia Sharma is the new Chair of Molecular Infection Biology II and member of the medical faculty at the Institute of Molecular Infection Biology
Cynthia Sharma obtained her PhD from the Max Planck Institute for Infection Biology and University of Bielefeld and performed her doctoral studies at the same Max Planck Institute and the National Institutes of Health in the USA. She became an independent Young Investigator at the Research Centre for Infections Diseases (ZINF) at the University of Würzburg. Her work focuses on the identification and characterisation of non-coding RNAs and RNA-binding proteins in pathogenic bacteria, more recently in Helicobacter pylori and Campylobacter jejuni. Her lab uses innovative deep-sequencing based approaches and 3-D infection models based on tissue engineering to study the role of RNAs in pathogenesis
New RNA-centric Research Institute
The Helmholtz Institute for RNA-based Infection Research (HIRI) in Würzburg, which will be led by IMIB Director Jörg Vogel, was officially established on 24th May 2017. (Photo Rudi Merkl)
The new Institute, which is a collaboration between the Helmholtz Centre for Infection Research in Braunschweig and the University of Würzburg, will be located on the university’s medical campus. Its research will focus on the role of ribonucleic acids (RNA) in bacterial and viral infections as well as their functions in the host immune response. The aim is to convert the relatively new understanding of the cellular role of RNA, which has emerged over the last two decades, into a better molecular understanding of infections, and to exploit RNA’s chemical properties to devise new therapeutic intervention strategies.
The event for the establishment of the institute was attended by the Bavarian Minister for Economic Affairs, Media, Energy and Technology, Ilse Aigner, Managing Director of the Helmholtz Society Franziska Broer, Bärbel Brumme-Bothe from the Federal Ministry of Education and Research, the President of the University of Würzburg Professor Alfred Forchel, the Scientific Director of the HZI Professor Dirk Heinz, founding HIRI Director Jörg Vogel the as well as more than 100 other guests. The official signing of the agreement took place in the Fürstensaal of the Würzburg Residence Palace.
For further information (in German):
Zonta prize for ZINF Young Investigator Sina Bartfeld
The ZINF Young Investigator Sina Bartfeld has been awarded the Zonta Prize of the Zonta Club Würzburg. This prize is awarded annually to a highly qualified female scientist of the University of Würzburg.
The Zonta Club is an international organization of professional women with the goal to empower women through service and advocacy. The Zonta Club Würzburg awards the prize since 1995 to support women in the faculties of medicine, biology, chemistry and pharmacy, mathematics and informatics as well as physics and astronomy. The prize is endowed with 2000 Euros. Sina Bartfeld wants to use this prize to support festivities at the ZINF and IMIB so that parents are stimulated to bring their kids, hoping that this will enhance the visibility of mothers in science. Jörg Vogel, speaker of the ZINF, gave the laudation at the award ceremony.
DGHM and VAAM Poster Prize
Congratulations to Bernardo Ramírez-Zavala (AG Morschhäuser), who won one of the ten awarded poster prizes at the recent 5th Joint Con-ference of the German Society for Hygiene and Microbiology (DGHM) & Association for General and Applied Microbiology (VAAM), which took place from 5-8 March 2017 in Würzburg.
Bernardo received the award for the following poster, which was selected from a total of more than 600 :
Bernardo Ramírez-Zavala, Austin Mottola, Sabrina Schneider, Julia Haubenreißer, Stephanie Allert, Sascha Brunke, Bernhard Hube, Knut Ohlsen, Joachim Morschhäuser: “The Snf1-activating kinase Sak1 is essential for metabolic adaptation and in vivo fitness of Candida albicans”.
IMIB scientists visit private donor Baldwin Knauf
Jörg Vogel and ZINF Young Investigator Sina Bartfeld have visited Baldwin Knauf at the gypsum factory "Knauf Werke" in Iphofen. Baldwin Knauf generously supports research at the Institute of Molecular Infection Biology of the University Würzburg through donations.
Knauf gypsum is a worldwide company with more than 26000 employees and a business volume of about 6 billion Euros. Baldwin Knauf, the son of one of the founders, Karl Knauf, gave Jörg Vogel and Sina Bartfeld a private tour through the families plant in Iphofen. Baldwin Knauf currently supports the research of IZKF Young Investigator Christian Perez who is trying to better understand Candida albicans infections and research by ZINF Young Investigator Sina Bartfeld and Emmanuel Saliba to characterize the changes that the carcinogenic pathogen Helicobacter pylori induces in stem cells.
Jörg Vogel awarded the Gottfried Wilhelm Leibniz Prize
Jörg Vogel has been awarded the Gottfried Wilhelm Leibniz Prize, the most prestigious research award in Germany.
ERC Starting Grant
ZINF Young Investigator Nicolai Siegel has been awarded a highly prestigious European Research Council (ERC) Starting Grant for 1.5 million Euros over 5 years to study how genome organisation influences antigenic variation in parasites.
Many pathogens, including parasites, bacteria and fungi, switch the identity of their surface molecules so that they are able to continuously evade the host immune system, a process called antigenic variation. Parasites such as Trypanosoma brucei, the causative agent of sleeping sickness, express a single version of a surface protein at any one time. This protein is recognized as foreign by the immune system, which produces antibodies to help eradicate the pathogen. However, the parasite is able to periodically switch the identity of the surface coat protein, to a version that is no longer recognized by the current repertoire of antibodies in the body. This enables it to evade the immune response until antibodies are generated against the new surface protein.
Despite the phenomenon of antigenic variation being recognized over a century, it is not well understood how a parasite ensures a single surface protein is expressed at a time and how it ‘decides’ which surface protein should be subsequently produced. Using a number of state-of-the-art approaches, Nicolai Siegel will investigate how the parasite’s genome is organized in three-dimensional space and if the relative location of surface protein genes in the nucleus is a determining factor of which surface protein is expressed and visible to the immune system at any one time. Elucidating the general principles of nuclear architecture and its role in antigenic variation will provide new therapeutic strategies that will interfere with a fundamental immune evasion strategy of the parasite and help facilitate its clearance.
The EU-funded ERC Starting Grants aim to support up-and-coming research leaders who are establishing an independent research group in Europe. This year just under 3000 applicants applied for the prestigious grants in the sections Physical Sciences & Engineering, Life Sciences and Social Sciences & Humanities and 325 projects were funded through the scheme, 9 of which went to researchers in the field of infection and immunity.
For more information please visit the website of Nicolai Siegel:
Double awards for Mona Alzheimer
Mona Alzheimer, a PhD student in the Sharma group, has scooped two prizes at recent scientific meetings, the 12th International Workshop on Pathogenesis and Host Response in Helicobacter Infections and IZKF retreat.
Mona received an award for one of the best short talks (from a total 3 awarded) at the "12th International Workshop on Pathogenesis and Host Response in Helicobacter Infections" in Helsingør, Denmark, from June 29 – July 2, 2016. As part of her prize she received a nice glass plate containing an engraved Helicobacter, please see her for a viewing. Her presentation was entitled "Novel tissue-engineered human 3D infection models to study pathogenesis of Helicobacter pylori and Campylobacter jejuni.
In addition she was also awarded one of the two poster awards at the 2016 IZKF retreat in Kloster Banz on June 10/11, 2016
Jörg Vogel is elected to the European Academy of Microbiology
The European Academy of Microbiology is closely aligned with the Federation of European Microbiological Societies (FEMS) and consists of senior microbiologists within Europe. Its objectives include providing advice for the Federation and a united advisory source for governmental and other bodies. Additionally, the European Academy of Microbiology promotes excellence in microbiology in Europe through targeted programs and activities. Members of the academy are elected through a highly selective, peer-reviewed process, based on their records of scientific achievement and original contributions that have advanced microbiology.
Campylobacter post-transcriptional regulatory networks and RNA localization
New research published in Nature Communications from the ZINF group of Cynthia Sharma and the group of Markus Sauer from the Biocenter describes the role of the post-transcriptional regulatory CsrA-FliW network in flagellar regulation of the human pathogen Campylobacter jejuni – a major cause of bacterial gastroenteritis.
Post-transcriptional regulation in bacteria is often the result of a complex cross-talk between mRNAs, small RNA (sRNAs) and protein regulators. The widespread CsrA (Carbon storage regulator) protein is a global regulator that binds to the 5’ region of bacterial mRNAs and represses their translation. In many species its activity is controlled by two antagonizing sRNAs that sequester CsrA. How this global regulatory circuit is controlled in species that lack these sRNAs is unclear. Gaurav Dugar and colleagues globally analysed the RNAs that associate with CsrA in the Epsilonproteobacterium Campylobacter jejuni and found that the mRNA encoding the major flagellin acts both as a target and a regulatory “sponge” for CsrA together with the main CsrA-antagonist, the protein FliW. Using confocal and super-resolution imaging, they also show that the flagellin mRNA localizes to the cell poles in a translation-dependent manner that is impacted by the CsrA-FliW post-transcriptional regulatory system.
Dugar G, Svensson SL, Bischler T, Wäldchen S, Reinhardt R, Sauer M, Sharma CM (2016) The CsrA-FliW network controls polar localization of the dual-function flagellin mRNA in Campylobacter jejuni. Nature Communications 7:11667. doi: 10.1038/ncomms11667
Two PhD students from AG Morschhäuser, Irene Hampe and Christina Popp, received awards at the recent 13th ASM Conference on Candida and candidiasis, in Seattle, USA.
Irene received an ASM student travel grant and her contribution was selected for an oral presentation at the conference. Christina received one of four poster prizes that were selected from a total of 190 posters.
The titles of their presentations were:
- Irene Hampe: Simultaneous acquisition of drug and antifungal peptide resistance in Candida albicans by Mrr1-mediated overexpression of two different efflux pumps.
- Christina Popp: Fitness costs of drug resistance in clinical Candida albicans isolates.
Heidrun Moll and Nicolai Siegel have been awarded the Rudolf Leuckart Medal and Karl Asmund Rudolphi Medal, respectively, of the German Society of Parasitology.
The Rudolf Leuckart Medal is awarded to researchers for their long-standing efforts to promote Parasitology within Germany. The Karl Asmund Rudolphi Medal is awarded to young scientists who have made outstanding scientific contributions to parasitology. Both medals were presented during the Annual Meeting of the German Society of Parasitology held in Göttingen (9th – 12th March 2016).
For more information www.presse.uni-wuerzburg.de/einblick/single/artikel/preise-fuer-parasitologen/
New approach to understanding host-pathogen interactions
New research published in Nature from the IMIB group of Jörg Vogel describes a new method, dual RNA-seq, which provides insight into how pathogens change their gene expression patterns upon invading a eukaryotic cell and how the host cell responds to the infection.
Elucidating the molecular events by which a pathogen infects a host cell and the corresponding response is crucial to understanding of host – pathogen interactions and the development of intervention strategies. Many genes can be identified that are required for the efficient infection of an animal, however, in many cases the difficulties arise in trying to understand the precise role of the encoded protein or RNA in the infection process. Many examples exist where deletion of the gene fails to provide an observable effect in cell-based laboratory assays. This is especially true for many of the recently identified non-coding RNAs – whose function is to fine-tune gene expression - rendering their functions obscure.
Members of the Vogel lab, notably PhD student Alexander Westermann and several bioinformaticians at the IMIB, explored the feasibility of using next generation sequencing technologies to describe the RNAs present in both Salmonella and infected human cells at different time points during the infection. The resulting changes in both the bacterial and host transcriptomes suggest a dynamic host-pathogen interplay at the level of gene expression. Importantly, a bacterial small RNA, PinT, was highly upregulated upon internalization by the host cell. Deletion of the PinT gene revealed dramatic changes in both the host and pathogen transcriptomes, despite not showing an effect in cellular based assays, with subsequent molecular analysis identifying it to be an important regulator of virulence programs. The loss of the sRNA also caused corresponding significant changes in the host cytokine response and signaling pathways in the human cells.
Therefore, dual RNA-seq can be used to comprehensively chart the dynamic RNA expression landscape of both a bacterial pathogen and its eukaryotic host during the course of infection. The one-step nature of dual RNA-seq should enable high-throughput studies to unravel such hidden gene functions in pathogen and host simultaneously, during infection with Salmonella and many other pathogens.
For more information please follow these links:
Raúl Cosentino (AG Siegel) has been awarded a Georg Forster Research Fellowship from the Alexander von Humboldt Foundation.
The Georg Forster Research Fellowship is a programme that supports excellent post-docs and experienced scientists from developing countries. It aims to facilitate the exchange of knowledge and methods between Germany and the country of origin.
Christian Perez has received funding from the Volkswagen Foundation’s Experiment! program.
The Experiment! program seeks to support entirely new research approaches involving the establishment of counterintuitive hypotheses as well as unconventional methodologies or technologies. Christian received funding for his project “A feast within us: Targeting microbial interactions inside us to discover smarter therapeutic strategies”.
EMBO Young Investigator
Ana Eulalio (BioSysNet Young Investigator) has been selected as an EMBO Young Investigator.
Ana is one of 23 young investigators joining the EMBO YIP network that represents some of the best young group leaders contributing to research in Europe and beyond. The programme targets researchers under forty years of age who have established their first laboratories in the past four years.
The Young Investigators receive a range of benefits, including an award of 15,000 Euros and the opportunity to apply for additional funds to help start their first independent research laboratories. Laboratory management and non-scientific skills training as well as PhD courses offer the young group leaders and their students the chance to develop professional skills. The scientists also receive access to core facilities at EMBL and funding for themselves and their group members to attend conferences.
For more information please read more EMBO news
Editorial Board Appointment
Prof. Heidrun Moll has been appointed to the Editorial Board of the new open access journal Parasite Epidemiology and Control.
The World Federation for Parasitologists (WFP) has launched the new open access journal Parasite Epidemiology and Control. The journal will publish articles on all aspects of parasite and vector epidemiology. Professor Marcel Tanner of the Swiss Tropical & Public Health Institute leads the journal as its Editor-in-Chief.
In addition to being a founding editorial board member of the new journal, Heidrun Moll also serves on the editorial boards of the European Journal of Cell Biology and Current Immunology Reviews.
Poster Prize News
Congratulations to Lena Böhm (AG Perez) and Irene Hampe (AG Morschhäuser), who both won poster prizes at the recent joint 49th Scientific Conference of the German Speaking Mycological Society and 1st International Symposium of the CRC/Transregio FungiNet.
The conference took place from 16th - 19th September 2015 in Jena. Irene and Lena won two of the seven prizes from a total of 85 posters.
Their titles were:
Lena Böhm: A recently evolved transcriptional repressor governs Candida albicans cell surface remodeling and determines the outcome of interactions with host immune cells.
Irene Hampe: Regulation of an efflux pump that mediates antimicrobial peptide resistance in Candida albicans.
Best talk prize at the ISMB/ECCB
Malvika Sharan (AG Eulalio and Vogel) has been awarded the best talk prize in the Automated Function Prediction Proceedings at the joint annual international conference on Intelligent Systems for Molecular Biology (ISMB) and the European Conference on Computational Biology (ECCB), which took place in Dublin, Ireland. Malvika presented APRICOT, which is the tool that she has developed for identifying RNA-binding proteins and protein-RNA interactions.
Graduate School of Life Sciences Fellowships
Congratulations to IMIB PhD candidates Laura Müller and Sarah Eisenbart who have been awarded PhD fellowships from the University of Wurzburgâ€™s Graduate School of Life Sciences.
Laura obtained her undergraduate and Master degrees in Biomedicine from the University of Würzburg. She will join the Siegel lab where she will focus on the impact of nuclear architecture on gene expression in Trypanosomes.
Sarah also obtained her undergraduate and her Masters degree in Biomedicine from the University of Würzburg. Sarah will join the Sharma lab where she will investigate how small RNAs and RNA-binding proteins control virulence in Helicobacter.
Both were successful in a highly competitive fellowship selection process. The graduate school received over 350 applications from which 60 candidates were selected for interviews for a total of 12 fellowships.
Cynthia Sharma from the Research Center for Infectious Diseases (ZINF) is one of ten researchers to be awarded the most important prize for young investigators in Germany. The prize is awarded annually by the German Research Foundation (DFG) and the Federal Ministry of Education and Research (BMBF) as a distinction for outstanding achievement.
Evolution of cellular circuits
Christian Perez has received funding from the Bavaria California Technology Center (BaCaTeC) to facilitate his work with Prof. Polly Fordyce at Stanford University on the molecular mechanism involved in the evolution of gene regulatory circuits in Candida albicans.
The ability to control gene expression is essential for most cells to function properly. At its core, this control is provided by sequence-specific DNA binding proteins. Recent work has shown that small changes in the binding specificities of these proteins over evolutionary timescales can drive the emergence of new traits in many organisms. This finding raises fundamental questions about the mechanisms that make this possible: What type of modifications can these proteins undergo and how do these changes impinge upon the regulatory circuitry of an organism? In collaboration with Dr. Fordyceâ€™s group at Stanford University, the Perez lab will determine the full profile of DNA sequences that a family of yeast transcription factor proteins can recognize along with their specificity and binding affinity. This information will allow them to infer a logical series of steps that led to the divergence of this family of proteins and the novel functions that they acquired.
The mission of BaCaTeC is to increase and promote cooperation between researchers located in Bavaria and California. It provides a basis for identifying potential partners and assists with initial contacts if necessary. BaCaTeC also sponsors projects with seed money to start up new collaborations.
Antibiotic Resistance Research
Antibiotic resistant bacteria are a matter of increasing medical and public concern. The issue is highlighted in DIE ZEIT (20th Nov) and covers the link between industrialised animal husbandry and the occurrence of multidrug resistant human pathogens such as methicillin-resistant S. aureus (MRSA) – a topic of research at IMIB.
The article includes recent work from the BMBF-funded MedVetStaph consortium which brings together experts from microbiology, epidemiology and veterinarian sciences to study the epidemiology of livestock-associated (LA)-MRSA. The research has identified an association between high antibiotic use in intensive mass animal farming and the selection and spread of LA-MRSA. These multiresistant bacteria are detectable in food samples, but also colonise companion animals and humans, finally finding their way into hospital settings where they add to the increasing burden of healthcare associated infections.
The IMIB contributes to the MedVetStaph programme through a project led by Dr. Wilma Ziebuhr, dealing with the early detection and analysis of novel resistance genes against last resort antibiotics in environmental samples from farm holdings. The goal of the project is to assess the risk potential of bacterial populations in animal husbandries as reservoirs for the generation and spread of novel antibiotic resistance genes.
Robert Koch Postdoctoral Prize
Kai Papenfort has been awarded the Robert Koch Postdoctoral Prize for his work on the role of small RNAs in Salmonella performed during his time at the IMIB.
The Robert Koch Postdoctoral Prize is awarded each year for outstanding post-doctoral work by the next generation of scientists in the areas of Microbiology, Immunology and Virology. Prof. Jörg Hacker, President of the German Academy of Sciences - Leopoldina, presented the award. Several IMIB and ZINF researchers have previously received the prize including Cynthia Sharma, Christoph Schoen, Ulrich Dobrindt, Christof Hauck and Sven Hammerschmidt. For more information please click here
EMBO Practical Course Non-coding RNA in Infection
The first EMBO Practical Course Non-coding RNA in Infection was held at the Institute for Molecular Infection Biology during October. The course included lectures from many leading scientists in RNA Biology
Many leading researchers volunteered their time to participate in the teaching of the course including Shoshy Altuvia, Ana Eulalio, Matthias Hentze, Michael Kiebler, Miguel Mano, Hanah Margalit, Nikolaus Rajewsky, Pascale Romby, Cynthia Sharma, Rotem Sorek, Jörg Vogel, Olivier Voinnet and Gerhart Wagner. Many IMIB staff also took part in helping running the practical aspects of the course ensuring its success.
The aim of the course was to provide a limited number of students with hands-on training in the techniques required to identify and characterise eukaryotic and prokaryotic RNAs involved in the infection process. The motivation for the course was the recognition that regulatory RNA molecules from pathogenic bacteria have important functions in virulence control while host non-coding RNAs are involved in the response to infection. However, for many relevant pathogens a systematic and comprehensive understanding of the role of non-coding RNAs in the infection process has not been achieved. Moreover, in many of the cases where non-coding RNAs have been identified, their targets and functions are yet to be determined. In the end it was a lively and fun week attended by eighteen mid-to-late-stage PhD students and early postdocs from both the prokaryotic and eukaryotic fields.
RNase Controls Malaria Parasite Antigen Expression
The molecular basis for how the malaria parasite Plasmodium falciparum evades the host immune system is not well understood. Work from ZINF Young Investigator Nicolai Siegel together with researchers at the Pasteur Institute published in Nature reveals an unanticipated role for an RNase in the process.
Plasmodium falciparum periodically switches expression between different var genes that code for the erythrocyte membrane protein 1 (PfEMP1). While the Plasmodium genome contains 60 var genes, only a single var-family member is expressed at any one time on the surface of infected erythrocytes and the change in expression enables the parasite to evade the adaptive immune response. The mechanism by which this monoalleic expression occurs is poorly understood but evidence suggests that it involves various epigenetic mechanisms involving histone modifications. In the current study, researchers at the Pasteur Institute in Paris asked the question whether other post-transcriptional mechanisms are involved. They identified a non-canonical exoribonuclease, which they called PfRNase II. The enzyme localises to the nucleus, where it degrades single stranded RNA. Monoallelic expression of var genes is disrupted in parasites expressing a deficient version of the exoribonuclease leading to the simultaneous expression of several family members. Importantly, there is an inverse relationship between levels of PfRNase II and the upsA-type var genes in parasites from severe malaria patients, indicating an important role for the enzyme in the infectious disease.
Evolution of Antibiotic Resistance
Reporting in the journal Cell, the laboratory of ZINF Young Investigator Daniel Lopez has revealed a new route by which the bacterial pathogen Staphylococcus aureus can evolve vancomycin resistance in the absence of the antibiotic but involving interactions between different subpopulations of cells.
The prevalence of antibiotic resistance is currently an important issue, which threatens our ability to treat infectious diseases. Consequently, the World Health Organisation has recently stated that we could be entering the post-antibiotic era. It is therefore important to understand how antibiotic resistance evolves to enable us to identify potential new strategies to combat these resistant pathogens.
Traditionally antibiotic resistance has been seen as the acquisition of mutations or new genes that render a microbe less susceptible to antibiotic treatment. These genetic variants are selected and propagated in the presence of broad-spectrum antibiotics due to a strong selection pressure. However, Gudrun Koch and colleagues from the Lopez lab have revealed that decreased susceptibility can occur even in the absence of antibiotic due to interactions between different bacterial strains within a population.
Working with a virulent antibiotic resistant strain of the Gram-positive pathogen Stapylococcus aureus, methicillin resistant Staphylococcus aureus (MRSA), they have observed the strain evolve over time in conditions that favour serious chronic infections in patients. The initial strain evolves to secrete more toxins and natural antibiotics to obtain a growth advantage, in response to this the original strain adapts to become resistant to these secreted products. As a consequence the final strain has the characteristics of pathogens that are resistant to multiple antibiotics including the last resort antibiotic vancomycin, which is the last line of defense against drug-resistant S. auerus. This has serious potential implications for the treatment of such infections and suggests that interactions between bacteria at the sites of infections could also be important to understanding the process of pathogenesis as well as the development of antibiotic resistance.
Poster Prize for Sara Eisenbart
Congratulations to master student (M.Sc. Biomedicine) Sara Eisenbart from AG Sharma who was recently awarded one out of three poster prizes at the "11th International Workshop on Pathogenesis and Host Response in Helicobacter Infections" in Helsingor, Denmark. Her poster was entitled "A nickel-regulated small RNA represses expression of major virulence factors in Helicobacter pylori ".
At this Helicobacter meeting all posters are presented as 3 to 5 min long short presentations within special poster sessions.
Jörg Vogel elected to the German Academy of Sciences
Jörg Vogel has been inaugurated into the German Academy of Sciences – Leopoldina. He received his certificate from the President of the Society Jörg Hacker during a ceremony in Halle.
Founded in 1652, the Leopoldina is one of the oldest academies of science in the world. It is dedicated to the advancement of science for the benefit of humankind and to the goal of shaping a better future. With some 1,500 members, the Leopoldina brings together outstanding scientists from Germany, Austria, Switzerland and many other countries. For more information please visit its website (http://www.leopoldina.org/de/home/)
Funding Renewal for Collaborative Research Centre 34
The Collaborative Research Centre 34 - Pathophysiology of Staphylo-
cocci in the Post-Genome-Era has been successfully evaluated and approved for the final round of funding by the DFG. IMIB members direct four projects in the network.
Within the Collaborative Research Centre Transregio 34 network, functional genomics approaches are being used to provide fundamental insight into the physiology and infection biology of the pathogenic bacterium Staphylococcus aureus. Its objective is to substantially increase our knowledge of the biology of S. aureus, for the future improvement of prevention and treatment of infections. The network involves researchers from the University of Würzburg, University of Greifswald, University of Tübingen and the University Hospital Münster.
Several IMIB members have projects in the network these include:
Knut Ohlsen, Phosphoproteomic analysis of Staphylococcus aureus: Functional characterization of kinases and identification of their substrates and In vivo imaging of Staphylococcus aureus infections.
Wilma Ziebuhr, Regulation of methionine metabolism in staphylococci: Impact on fitness and virulence.
Jörg Vogel, Post-invasion events in Staphylococcus aureus infected host cells – A combined transcriptomics/ proteomics in vivo approach.
ESCMID Grant for Cynthia Sharma
ZINF Young Investigator Cynthia Sharma has been awarded a European Society of Clinical Microbiology and Infectious Diseases (ESCMID) grant
The ESCMID research grants are aimed to help young and excellent investigators to pursue groundbreaking research in the fields of clinical microbiology and infectious diseases. Cynthia received the funding to support her IZKF collaborative research project on new 3D-infection models based on tissue-engineering to study pathogenicity of Helicobacter pylori and Campylobacter jejuni
For further information please follow this link https://www.escmid.org/index.php?id=1291
Helicobacter host adaptation
Understanding how bacterial pathogens adapt and take advantage of changing environmental conditions not only provides new insight into the cause and persistence of infectious diseases but also identifies new potential intervention strategies. New research published in the recent issue of the Proceedings of the National Academy of Sciences (PNAS 111(4):E501-10) from the ZINF young investigator group of Cynthia Sharma demonstrates how variable DNA sequences in the gastric pathogen Helicobacter pylori determine the outcome and fine-tuning of small RNA-mediated post-transcriptional gene expression control.
Many pathogens endure extreme variations in environmental conditions such as temperature, nutrient availability, and acidity or different niches within the host. Rapidly adapting to these changes is important for the colonisation, persistence, and spread of a pathogen within the host. This is especially important for the human pathogen Helicobacter pylori , which can persistently colonize the extreme acidic environment of the stomach in about 50% of the worldâ€™s population leading to gastritis, ulcers, and even gastric cancer. Similarly to other pathogens, it is important for H. pylori to be able to generate a level of phenotypic variability within a population through phase-variation. This process increases genomic variation, thereby facilitating the selection of beneficial mutations that enable the pathogen to adapt to new conditions. For example, H. pylori possess more than 50 genes with hypervariable simple sequence repeats (SSRs) which can undergo length variation as a consequence of replication errors. Length variation within SSRs can affect the expression of virulence associated genes and the mechanism by which this occurs been mainly viewed as mutations in DNA sequences that disrupt the coding regions of genes or their regulatory elements. However, their impact on RNA regulation is less understood. In the current study, PhD student Sandy Pernitzsch and Cynthia Sharma have identified a new mechanism of how variable SSRs can affect small RNA-mediated post-transcriptional regulation of a chemotaxis receptor in H. pylori.
Pernitzsch and Sharma describe how a highly expressed small RNA, RepG, from H. pylori interacts with the mRNA and thereby represses the expression of the pH-sensing chemotaxis receptor tlpB, a virulence factor involved in colonisation and inflammation of the stomach. Interestingly, the RepG sRNA, which was identified in a previous global transcriptome study by the authors, directly binds to a stretch of 12 guanines in the 5â€™ untranslated region of the tlpB mRNA, which corresponds to one of the variable SSRs in H. pylori. However, due the unusual location of this SSR its mechanism and impact on gene expression was unclear since it did not easily fit with previous models of phase variation. Analysis of the genome sequences of more than 30 Helicobacter strains revealed that while the sequence of the small RNA is highly conserved, the length of the SSR in the tlpB mRNA varies between 6-16 guanines. Based on this observation Pernitzsch and Sharma could show using a variety of in-vivo and in-vitro experiments that the length of this homopolymeric repeat determines the outcome of small RNA-mediated regulation (activation or repression) by affecting the translation of tlpB mRNA.
Therefore, this study links for the first time small RNA-mediated regulation and phenotypic variation via variable repeats. Rather than the phase variable ON-OFF switch of regulation observed for frame-shift mutations within genes, changes in the length of these homopolymeric G-rich motifs in the 5â€™ untranslated region of mRNAs can fine-tune the expression of genes important for the colonisation of the host. Given the number of SSRs in pathogen genomes this mechanism is likely to a more widespread phenomenon leading to rapid adaptation.
Pernitzsch SR, Tirier SM, Beier D, Sharma CM (2014)
A variable homopolymeric G-repeat defines small RNA-mediated posttranscriptional regulation of a chemotaxis receptor in Helicobacter pylori
Proc Natl Acad Sci U S A. 2014 111(4):E501-10
DGHM Förderpreis 2013
Congratulations to Cynthia Sharma who has recently received the Förderpreis 2013 of the DGHM foundation at the Annual Meeting of the Deutsche Gesellschaft für Hygiene und Mikrobiologie.
The German Society for Hygiene and Microbiology (DGHM) e. V. is the oldest society in the field of Medical Microbiology being founded in 1906. The annual prize is awarded to excellent young scientists in biomedical science. Cynthia received the award for her outstanding work on riboregulation in pathogenic bacteria and impressive international reputation established during her young career. Her research focuses on the identification of small regulatory RNAs and associated RNA-binding proteins and their functions during stress response and virulence of the human pathogens, Helicobacter pylori and Campylobacter jejuni.
For further information please click the following links:
Congratulations to Patrick Tan (AG Sharma) and Malvika Sharan (AG Vogel and AG Eulalio) who both won poster prizes at the recent Scientific Crosstalk, 8th International Symposium.
Scientific Crosstalk is an international meeting organized by the students of the Graduate School of Life Sciences at the University of Würzburg, it took place on the 9th and 10th of October, 2013. Patrick and Malvika won two of the four prizes from a total of 80 posters and received a Nikon Coolpix camera as a prize. Their titles were:
Patrick: A small RNA which is regulated by the acid responsive ArsRS two-component system in Helicobacter pylori.
Malvika: Computational identification of RNA interacting bacterial effectors based of functional domains
Congratulations to Tobias Ölschläger and his lab for winning a Poster Prize at the recent Deutsche Gesellschaft für Hygiene und Mikrobiologie (DGHM) Conference.
The 65th Annual Meeting of the DGHM took place from 22nd - 25th September 2013 in Rostock. The winning poster was titled “Probiotic Escherichia coli strain Nissle 1917 binds to gluconate of mucin 2 / human mucus not via pili but its flagellum“ and included work from Anja Troge and Stefan Rund from the Ölschläger lab
Congratulations to Mona Alzheimer (AG Sharma) and Sandy Pernitzsch (AG Sharma) who both won poster prizes at the recent International Workshop on Campylobacter, Helicobacter and Related Organisms.
The "CHRO 2013: 17th International Workshop on Campylobacter, Helicobacter and Related Organisms" took place from 15th - 19th September 2013 in Aberdeen, UK. Mona and Sandy won two of the fifteen prizes from a total of 297 posters.
Their titles were:
Mona Alzheimer: New 3D-infection models based on tissue-engineering to study pathogenesis of Helicobacter pylori and Campylobacter jejuni
Sandy Pernitzsch: Targeting of a homopolymeric G-repeat by a small RNA mediates repression of a chemotaxis receptor in Helicobacter pylori
ERC Starting Grant
Congratulations to Daniel Lopez who has been awarded a highly prestigious European Research Council (ERC) Starting Grant for 1.5 million Euros over 5 years to study the role of cell signalling in bacterial pathogenesis.
The EU-funded ERC Starting Grants aim to support up-and-coming research leaders who are establishing an independent research group in Europe. This year over 3000 applicants applied for the prestigious grants in the sections Physical Sciences & Engineering, Life Sciences and Social Sciences & Humanities and 287 projects were funded through the scheme, 46 of which went to researchers in Germany.
Daniel Lopez will study the assembly and organization of discrete lipid microdomains that are present in the membranes of bacterial pathogens such as Staphylococcus aureus. These â€˜lipid-raftâ€™ membrane domains are important for the organization of signaling pathways and their disruption leads to changes in the physiology of the pathogen. For example, treatment of bacteria with small molecule drugs that disassemble these microdomains leads to a concomitant decrease in processes associated with bacterial virulence. Therefore, a better understand of the organisation of signalling pathways and how they affect pathogenesis may provide an alternative strategy for generating antimicrobial drugs.
For more information please visit the website of Daniel Lopez : http://www.imib-wuerzburg.de/research/lopez/group-leader/
And news on the University Website :
Congratulations to Erik Holmqvist (Vogel lab) who has been awarded a highly prestigious Wenner-Gren Fellowship by the Wenner-Gren Foundation in Sweden.
The Wenner-Gren Foundations (WGF) seek to promote international cooperation in the area of scientific research. They award up to five fellowships per year, the stipend provides young biomedical researchers with an opportunity to receive a high quality post-doctoral education abroad before returning to conduct research in Sweden. The stipend is for a maximum of three years and it is required that at least one year is spent in a foreign country. After the end of the stipend, each fellow has the possibility to apply for two further years of funding to work as a researcher in a Swedish institution.
Non-coding RNAs Hit The Sweet Spot
New research published in Cell from the IMIB group of Jörg Vogel provides new insight into how bacteria rapidly respond to sugar stress by using a novel RNA-based mechanism of gene activation to rapidly export toxic sugars.
Control of glucose homeostasis is a key regulatory function that has been described in all kingdoms of life. The uptake of glucose is accompanied by a phosphorylation event that is vital for its intracellular retention. However, while phosphosugars are key metabolic intermediates, their intracellular levels must be tightly regulated since high levels are toxic and strongly impair cell growth and cause DNA damage. To relieve the sugar-induced stress, bacteria prevent further expression of sugar transporters in the membrane, which is achieved by extensive transcriptional and post-transcriptional control. However, given the protein stability of the membrane transporter, which only decreases by 50% in three generations, this mechanism cannot be responsible for immediate relief. Therefore, how cells contend with acute sugar stress is not known.
Bacteria contain a large number of regulatory small RNAs (50-250nts) that are involved in the post-transcriptional regulation of gene expression. These small RNAs (sRNAs) typically repress the expression of mRNAs by either base-pairing with their targets and preventing the binding of ribosomes or facilitating the recruitment of RNA decay factors. For the few sRNAs that positively affect gene expression these function by relieving previous inhibitory structures that prevent the translation of specific RNAs.
SgrS is a small RNA that accumulates under conditions of sugar stress and has been shown to negatively regulate the expression of the glucose transporter PtsG, however, when the Vogel lab analysed the SgrS regulon, among the know targets, they identified an unknown gene that was induced by the sRNA. Further analysis of this gene, YigL, identified it as the long sought after phosphatase that dephosphorylates glucose-6-phosphate and thereby facilitates sugar export, providing a rapid way to relieve sugar stress. Importantly the induction of YigL occurred by a novel mechanism, whereby SgrS binds to a sequence just upstream of the YigL gene and inhibits the constitutive turnover of the mRNA by the ribonuclease RNase E, resulting in a rapid increase in yigL mRNA levels. Furthermore, the binding of the sRNA to yigL containing transcript was shown to be essential for sugar efflux and the recovery from sugar-stress.
The novel mechanism by which an sRNA inhibits the constitutive turnover of an mRNA provides an extremely rapid mechanism to alter gene expression in response to changing environmental conditions. Current studies suggest that it may be more wide-spread since other sRNAs have already been identified that activate gene expression by stabilising transcripts. Importantly, this activation mechanism of gene expression does not require the synthesis of new regulators, thereby rapidly relieving environmental stress without relying on the turnover of the stable sugar transporters in the membrane, which may be important for long term environmental adaptation to chronic high sugar levels.
FEBS Young Investigator Award
Congratulations to Ana Eulalio who has received the FEBS Young Investigator Award for her post-doctoral work on the role of miRNAs in cardiac regeneration which was recently published in the journal Nature. (LINK)
The Federation of European Biochemical Societies (FEBS) is one of the largest organizations in European life sciences, with more than 36,000 members distributed among over 35 national biochemistry and molecular biology societies across Europe and neighbouring regions.
The aim of the Young Investigator Award is to provide recognition to FEBS Long-Term Fellows who have conducted excellent research during the tenure of their Fellowship. The Award takes the form of a certificate and a single sum of money to contribute to the running of the laboratory.
Fellow of the American Academy of Microbiology
Jörg Vogel has been elected a Fellow of the American Academy of Microbiology. The Academy recognizes excellence, originality, and creativity in the microbiological sciences.
The Academy is the honorific leadership group within the American Society for Microbiology (ASM). The mission of the Academy is to recognize scientists for outstanding contributions to microbiology and provide microbiological expertise in the service of science and the public. The Academy administers ASMâ€™s awards and certification programs, convenes several colloquia a year for in-depth analysis of critical issues in microbiology, and honors distinguished scientists by electing them to Fellowship in the Academy.
In 2013, eighty-seven microbiologists have been elected to Fellowship in the American Academy of Microbiology. Fellows of the Academy are elected annually through a highly selective, peer-review process, based on their records of scientific achievement and original contributions that have advanced microbiology. There are over 2,000 Fellows representing all subspecialties of microbiology, including basic and applied research, teaching, public health, industry, and government service.
For a full list of newly elected fellows, please follow the below link:
Postdoctoral Fellowship Award
Congratulations to Masatoshi Miyakoshi (Vogel Lab) who has been awarded a prestigious post-doctoral fellowship from the Japanese Society for the Promotion of Science (JSPS). The fellowships are awarded to young Japanese researchers to conduct research at foreign universities or research institutions for a period of two years.
The Japanese Society for the Promotion of Science (JSPS) was originally established to facilitate the advancement of science in all fields of the natural and social sciences and the humanities. The society is funded by the Japanese Government to foster young researchers and to promote international scientific cooperation.
Fishing for complement aids malaria parasite survival
Malaria is a major health burden causing 655,000 deaths annually. During its lifecycle, transmission of the malaria parasite from an infected human requires that the Anopheles mosquito takes up erythrocytes that contain gametocytes, sexual precursor cells of the parasite, during its blood meal. Once in the mosquito, sexual reproduction of the parasite occurs in the midgut before subsequent entry into a new human host during feeding. Throughout itâ€™s lifecycle the parasite must evade components of the immune response found in the human blood. Until now it was not clear how Plasmodium evades the complement response, which involves the sequential assembly of a membrane bound complex that induces lysis of foreign infecting cells.
Previously, the sexual stages of the parasite had been shown to be sensitive to lysis by the complement system, which enters the mosquito midgut together with the blood meal. The Pradel lab were interested in how the parasite could avoid lysis to enable transmission to a new host. Initial observations agreed with previous work - that the alternative pathway of complement impaired gametogenesis, however, they were able to show that this was antagonized by a human host complement regulatory factor, FH. Normally, this regulatory factor inactivates complement components preventing them from targeting and lysing the hostâ€™s own cells. However, during infection the parasite expresses a protein, PfGAP50, which relocalises from an inner compartment to the plasma membrane once the gametocyte enters the mosquito midgut. This protein acts as the receptor for FH recruiting it to the parasites surface thereby protecting it from lysis and increasing the transmission of Plasmodium to the mosquito.
The Pradel lab, which has recently moved to RWTH Aachen University, is now aiming to utilise this complement evasion mechanism to block transmission of malaria parasites by the mosquito. They are evaluating complement evasion as a target for transmission blocking vaccines together with the nearby Fraunhofer Institute of Molecular Biology and Applied Ecology, who recently launched the Fraunhofer Future Foundation Malaria Project to develop and manufacture new malaria vaccines.
Graduate School of Life Sciences Fellowships
Congratulations to IMIB PhD candidates Benjamin Mielich-Süß and Caroline Tawk who have been awarded PhD fellowships from the University of Wurzburgâ€™s Graduate School of Life Sciences.
Benjamin was born in Ellwangen, Germany and obtained his undergraduate and Master degrees in Biology from the University of Würzburg. He will undertake his PhD in the Lopez lab where he will focus on the role of lipid rafts in the pathogen Staphylococcus aureus.
Caroline was born in Moscow, before studying for her Biology and Biochemistry degree at the Université Saint Joseph in Lebanon, this was followed by obtaining her Masters from the American University of Beirut in Molecular and Cellular Biology. Caroline recently joined the Vogel lab where she is investigating if bacterial effector proteins are able to target host RNAs.
Both were successful in a highly competitive fellowship selection process. The graduate school received over 200 applications from which 50 candidates were selected for interviews for a total of 10 fellowships.
DFG supports Staphylococcus research at IMIB and ZINF
The Deutsche Forschungsgemeinschaft (DFG) has funded two research projects in the Lopez and Ziebuhr labs that aim to provide new insight into Staphylococci infections.
Staphylococci are a prominent cause of acute and chronic infections, the persistence of infection is linked to the ability of these bacteria to form biofilms. Biofilms are surface-attached bacterial communities that are encased in an extracellular matrix, these structure render the bacteria refractive to the action of antimicrobials and the immune system. Therefore, the inhibition of biofilm formation has been targeted as a therapeutic strategy for the treatment of chronic infections.
The Lopez lab will focus on investigating the role of cellular differentiation and if distinct cell subpopulations play specific roles in biofilm formation and virulence in S. aureus. The Ziebuhr lab will examine the variability in gene expression and metabolism in different cell types during the formation and establishment of S. epidermidis biofilms.
The goal of the studies is to better understand the biofilm formation process and to identify new targets for antimicrobials.
Alex Westermann in double prize glory
The first week of October turned out to be particular productive for PhD student Alex Westermann (Vogel lab) as his poster won top prize at two consecutive meetings.
Alex presented his poster “Dual RNA-seq of Host and Pathogenâ€ at the 64th Annual Meeting of the German Society for Hygiene and Microbiology in Hamburg, before travelling directly to the 7th Meeting of the GBM Study Group RNA Biochemistry in Bonn. At both meetings he was awarded the prize for the best poster.
European Meeting on Gene Expression in T. brucei
The meeting is organized by Nicolai Siegel (ZINF) and Susanne Kramer (Dept. Cell and Developmental Biology) from the University of Würzburg. It brings together leading scientists from around Europe who have a joint interest in understanding the different mechanisms involved in the regulation of gene expression in the parasite Trypanosoma brucei, the causative agent of sleeping sickness which affects tens of thousands of people worldwide. Prof. Christine Clayton, from the University of Heidelberg, will present the keynote lecture.
For further question contact Nicolai Siegel at email@example.com
Further Funding for GSLS
The Graduate School of Life Sciences, University of Würzburg has been awarded further funding during the second phase of the German Excellence Initiative, which runs from 2012-2017.
The Excellence Initiative is run by the German Research Foundation (DFG) and the German Council of Science and Humanities with the goal of improving the quality of German Universities and promoting top-level research in the country. One approach is to fund dedicated graduate schools to promote early career researchers. Initially in 2006-2007 the Initiative funded 39 graduate schools throughout Germany and the federal and state governments decided in 2009 to continue the Excellence Initiative for a second phase. Upon submitting a proposal for the continued funding of the GSLS, the success of the school was evaluated by the DFG in a meeting in Bonn during Feb 2012. The GSLS sent a delegation of 25 representatives for the evaluation which include Prof. Vogel, Prof. Moll and Iris Gonzalez Leal from IMIB, the hard work and preparation of the team clearly paid off, since the presentations were well received and it was announced in June that the GSLS would be funded by the Excellence Initiative until 2017.
Stipend award for Alex Westermann
Alex Westermann (Vogel lab) has been awarded an Elite Advancement PhD. stipend from the Universität Bayern e.V. The Universität Bayern e.V. is an organization representing the group of leading Bavarian Universities. It awards up to 50 PhD. stipends a year to students covering all aspects of natural sciences and is partly based on the research proposal of the PhD student. Alex is using next generation sequencing technology and RNA deep sequencing to reveal the gene expression changes in both host and pathogen during the infection process.
Funding for Cynthia Sharma by the Bavarian Academy of Sciences and Humanities
Congratulations to Cynthia Sharma on being recognised by the Bavarian Academy of Sciences and Humanities and admitted to their Förderkolleg for her work on Helicobacter pylori.
The Bavarian Academy of Sciences and Humanities is one of the oldest scientific academies in Germany. In 2010 it launched its Förderkolleg, which is a program to support young talented scientists, and every year the academy selects and admits six talented young scientists. Cythniaâ€™s work on gene expression and non-coding RNAs in H. pylori was selected on the basis of the academies criteria for highly innovative research and she will receive additional funding over the next three years.
Long-term fellowship for Kai Papenfort
Kai Papenfort (Vogel lab) has been awarded a prestigious Human Frontiers Science Program (HFSP) long-term fellowship that will further support his career during his time in Princeton in the USA.
The HSFP long-term fellowships support successful applicants who propose a highly innovative project in a different field from their previous work. Kai will apply a systems biology approach to understand the role of stochasticity and its molecular basis during quorum sensing at the single cell and population levels. He will perform this work in the labs of Bonnie Bassler and Ned Wintergreen at Princeton University, USA.
W2 professorship for Alex Boehm
Congratulations to Alex Böhm on accepting an offer of the W2 Professorship of Synthetic Microbiology at the LOEWE-Centre for Synthetic Microbiology at the University of Marburg, to where he will move his lab in July 2012.
Alex joined IMIB in 2010 as an independent group leader where he focused his work on how bacteria sense and respond to altering environmental conditions. A key aspect of this response is how signaling pathways control the formation of surface associated bacterial communities, which is of great medical importance in combating specific chronic infections. In Marburg Alex will switch the emphasis of his research and take a synthetic microbiology approach to the de novo assembly of designer biofilms that can be used as an architectural scaffold for applied uses in areas such as tissue engineering.
W2 professorship for Sven Krappmann
Congratulations to Sven Krapmann on accepting an offer for the W2 Professorship of Clinical Microbiology and Immunonolgy at the University of Erlangen, Sven will move his lab to the University at the start of May 2012.
Sven has held the position of Young Investigator group leader at the Research Centre for Infectious Diseases (ZINF) in Würzburg since 2007. During this time his work has focused on understanding the processes associated with Aspergillus fumigatus pathogenicity, including the metabolic and signaling pathways involved in virulence and sexual development. Sven plans to shift the focus his work in Erlangen to the immune response of the host upon Aspergillus infection.
Scientific Coordinator at the IMIB
Dr. Stan Gorski has joined IMIB as a Scientific Coordinator from February 2012. He is affiliated with the Vogel lab, the IMIB and the Research Centre for Infectious diseases, ZINF.
Stan obtained his PhD from the Astbury Centre for Structural Molecular Biology at the University of Leeds, UK for mechanistic studies of protein folding reactions, before moving on for a post-doctoral position in the lab of Tom Mistleli at the National Cancer Institute at the NIH in Bethesda, USA where he used biochemical and live cell imaging approaches to study protein dynamics associated with chromatin structure and transcription in living cells. From 2006 to 2011, Stan was then a Scientific Editor at The EMBO Journal in Heidelberg where he was responsible for the chromatin, transcription and RNA content in the journal.
Junior Research Group Position (BioSysNet)
March 19, 2012: Anna Eulalio has been awarded and accepted a junior research group position based on funding from the Bavarian Molecular Biosystems Research Network (BioSysNet). She will start her lab at IMIB in April 2012 and will focus on the consequences of bacterial infection on host cell RNA metabolism.
Ana obtained her PhD from the University of Coimbra and Center for Neuroscience and Cell Biology in Portugal. Her subsequent post-doctoral studies at the EMBL, Max Planck Institute for Developmental Biology, Max Planck Institute for Infection Biology and the ICGEB in Trieste focused on miRNA mediated silencing mechanisms and the role of these small RNAs during bacterial infection and in cardiomyocyte biology. She is supported with 1.5 million Euros fromthe Bavarian Research Network for Molecular Biosystems, which is funded by the Bavarian State Government to provide a basis for closer research alliance between Bavarian Universities. As a part of this goal the program funds a number of regular junior research groups in addition to associated junior and senior research groups.
Her new research project is aimed at investigating the consequences of pathogenic bacteria on RNA metabolism pathways in infected host cells, as well as the reciprocal effect of these pathways on the life cycle of pathogenic bacteria, issues that remain largely unexplored. The ensuing knowledge will lead to an unprecedented understanding of fundamental aspects of host – pathogen interactions, which may constitute the basis for the development of novel therapeutic approaches against infection by bacterial pathogens.
New ZINF Young Investigator
February 15, 2012: Nicolai Siegel has arrived in Würzburg and started his new lab as a ZINF Young Investigator. The lab will focus on regulatory aspects of gene expression in African trypanosomes, the establishment of chromatin domains and potential links to antigenic variation.
Nicolai obtained his PhD from the Rockefeller University in New York in the lab of George Cross, where he mapped the chromatin signature associated with transcription starts sites in trypanosomes, before moving on the Pasteur Institute in Paris where he studying the role of non-coding RNAs in the malaria parasite Plasmodium falciparum with Artur Scherf.
Nicolai starts his lab with co-workers Ramona Derr and Johannes Thürich and IMIB wishes them all the best for future success.
Postdoctoral Erwin Schrödinger fellowship
December 23, 2011: Congratulations to Dr. Gudrun Koch, who has been awarded a prestigious postdoctoral Erwin Schrödinger fellowship by the Austrian Science Fund (FWF). This long-term fellowship will support Gudrun to investigate the role of recently discovered bacterial lipid rafts in pathogenesis, using Staphylococcus aureus as a model organism.
Gudrun obtained a B.Sc. degree from the University of Applied Sciences, Vienna, Austria. Following several research internships in Finland, United Kingdom and Germany, she completed her Ph. D. thesis at the University of Groningen in The Netherlands. Gudrun joined the ZINF Young Investigator Group of Dr. Daniel Lopez as a postdoctoral researcher in autumn 2011.
November 25, 2011: Congratulations to ZINF Investigator Cynthia Sharma who is one of three young scientists to be awarded with a Post-doctoral Prize by the Robert Koch Foundation in 2011, in recognition of their outstanding work. Cynthia won the post-doctoral prize in microbiology; Cecilia Chassin (Germany, Hannover) and Lars Dölken (Germany, Munich) were awarded the related prizes in the fields of immunology and virology, respectively. RNA was the big theme this year, since all three awardees were recognized to have broken new grounds on regulatory small RNAs in either pathogens or their hosts. The award ceremony took place in Berlin on November 11.
This yearâ€™s Main Prize went to Dr. Jorge Galan of Yale University (New Haven, USA) for his long-standing successful work on bacterial type three secretion systems. Shortly after receiving the prize, Jorge gave a well-received lecture at IMIB on Nov 15.
More information on the prizes and the Robert Koch Foundation is found at
Jörg Vogel has been elected as an EMBO Member in the 2011 annual round of elections, as announced this week. He is among 43 renowned life scientists from fourteen countries across Europe whose excellence in research has been acknowledged by the Organization this year.
New EMBO members are nominated and elected annually by existing members. EMBO members represent a high-profile cross section of researchers from all fields of molecular life sciences ranging from developmental biology, genomics, molecular medicine, neuroscience and plant biology to systems biology. Fifty-seven scientists from the EMBO membership have received the Nobel Prize.
Election announcement, EMBO
Press release, Uni Würzburg
Mol Micro Meeting Würzburg April 25-27, 2012
We would like to invite you to the next 'Molecular Microbiology Meeting Würzburg, to be held at the Institute of Molecular Infection Biology in 2012. The scientific programme will cover a diverse range of topics including bacterial cell biology, pathogenesis, gene regulation and signalling. [Read more]
8 Millionen für die Infektionsforschung !
SFB 630 wird weiter gefördert
Für weitere vier Jahre fördert die DFG den Sonderforschungsbereich 630 mit einer Summe von rund acht Millionen Euro.
Das Institut für Molekulare Infektionsbiologie ist mit 4 Arbeitsgruppen und der Koordination von Qulitätsmanagement beteiligt.
Weitere Informationen [Read more]