Upcoming events:
Reminder: Joint BIG NFM seminar March 6th
We would like to welcome all interested to a joint BIG and NFM seminar on the topic microbiology March 6th at Aud 2. Kristine Bonnevies Hus, Blindern Campus.
A light lunch will be served to pre-registered participants. Please send an email to margrethe.storm@ibv.uio.no to pre-register.
The program follows below with abstracts posted at our websites:
http://www.nfmikro.net
http://www.biokjemisk.com
Program NFM-BIG 6 Mars 2013.
Aud 2. Kristine Bonnevies Hus, Blindern Campus.
09:10 Welcome
09:10 – 09:40 Mike Koomey (IBV): Evolution and function of O-linked protein glycosylation in the genus Neisseria
09:40 – 10:00 Hans Petter Kleppen (UMB):
10:00 – 10:20 Helge Holo (UMB, TINE SA): Reducing ruminant methane emissions by probiotic Propionibacterium
10:20 – 10:50 Coffee
10:55 – 11:15 Håvard Kauserud (IBV, MERG):
11:15 – 12:00 Martin Homan-Marriot (NTNU):
Lunch 12:00 – 13:00
13:00 – 14:00 Æresprisutdeling til Reidun Sirevåg med foredrag : "Lady Montagu og historien om koppeviruset"
14:00 – 14:30 Gareth Griffiths (IBV); Development of biodegradable nanoparticles enclosing antibiotics against Mycobacterium.tuberculosis in macrophages and in a zebrafish model system
14:30 – 15:15 Maximiliano Gutierrez (MRC NIMR, London): Understanding intracellular persistence of mycobacteria
15:15 – 16:00 Årsmøte NFM
Kind regards
Hanne C. Winther-Larsen
&
Jan Haug Anonsen
Abstract:
Evolution and function of O-linked protein glycosylation in the genus Neisseria
Åshild Vik, Marina Aspholm, Bente Børud, Finn Erik Aas, Jan Haug Anonsen, Raimunda Viburiene, Wolfgang Egge-Jacobsen, and Michael Koomey
Center for Molecular Biology and Neuroscience and Department of Molecular Biosciences, University of Oslo, 0316 Oslo, Norway
The broad-spectrum O-linked protein glycosylation (pgl) system expressed by species within the genus Neisseria provides a unique model system in which to study the structure and function of protein-associated glycans as well as the underlying genotype – phenotype relationships. Genetic and biochemical analyses together with mass spectrometric- and serotyping-based glycan characterization have established that broad-spectrum pgl systems are found in all species within the genus but that pgl gene content and associated levels of glycan diversity may vary. Three major deviations in pgl genotype have been observed: the replacement of pglB by pglB2 (in N. meningitidis (Nm) and commensals), the loss of ORF2 / pglH (in N. gonorrhoeae (Ng) and Nm) and the absence of pglA and pglE in commensals. Based on these findings, a phylogenetically informative model for protein glycan evolution will be presented.
From a host-pathogen/symbiont perspective, two major gaps in knowledge relate to the forces driving protein glycan diversification and the functions glycosylation itself might have. Although most attention has been focused on modification of the type IV pilus pilin PilE, it is now clear that this system targets a large number of extracytoplasmic proteins as well. Although many of these ancillary targets are not predicted to be surface exposed, they are both periplasmically-localized and membrane-tethered as is PilE is in unassembled / disassembled state. Thus, it seems likely that protein glycosylation might serve a common, intracellular role. However, pgl null mutants display few if any distinct phenotypes. We found that expression of a particular hexa-histidine-tagged PilE was associated with growth arrest. By studying intra- and extragenic suppressors, we found that this phenotype was dependent on pilus assembly and retraction. Based on these results, we developed a sensitive tool to identify factors with subtle effects on pilus dynamics. Using this approach, we found that glycan chain length has differential effects on the growth arrest that appears to be mediated at the level of pilin subunit–subunit interactions and bidirectional remodelling of pilin between its membrane-associated and assembled states. Pilin glycosylation thus plays both an intracellular role in pilus dynamics and potential extracellular roles mediated through type IV pili. Together, these studies provide new perspectives on the functional correlates of bacterial protein glycosylation and glycoform diversification.
Gareth Griffiths. Dept. Biosciences, University of Oslo, Oslo, Norway.
Development of biodegradable nanoparticles enclosing antibiotics against Mycobacterium.tuberculosis in macrophages and in a zebrafish model system
The only currently available treatment against tuberculosis is the standard 6-8 month oral treatment with four antibiotics, including rifampicin. The need for such long treatment is hampered by patient non-compliance, leading to multi-drug resistance. One drawback of this standard protocol is that the antibiotics are rapidly degraded or excreted and must therefore be administered daily. An elegant alternative approach being pursued in a number of groups in different animal models is to encapsulate the antibiotics in biodegradable polymer nanoparticles (NPs). When administered either orally or via the lung- aerosol route these NPs appear to be able to cross epithelial barriers and to be taken via phagocytosis up by macrophages, the cells where pathogenic mycobacteria such as M.tuberculosis (M.tb) primarily reside. This field has been pioneered in particular by our collaborator Gopal Khuller in India, but also by other groups (see Griffiths et al, 2010. Nature. Rev. Microbiol. 8. 827). Striking results using a guinea pig model of M.tb by Khuller’s group have shown that M.tb infection of these animals can be cleared either by 45 daily doses of free antibiotics or by only 3-5 doses of antibiotics administered in poly lactide, co-glycolide (PLGA) NPs (Pandey et al, 2003. J. Antimicrobial. Chemother. 52, 981). Despite these, and other striking results in this field very little is known about the pathways taken by the NPs after the different routes of administration. To provide more insight into the mechanisms and routes taken in vivo by the NPs we have recently set up two complementary systems.1) Mouse primary macrophages infected with M.bovis BCG and 2) the zebrafish model of tuberculosis using red and green variants of M.marinum, a system pioneered by the group of Ramakrishnan (see Lesley and Ramakrishnan 2008. Curr. Opin. Microbiol). The great advantage of this system is that the colored bacteria can be visualized directly and non-invasively in the transparent fish embryos. After injection, the bacteria rapidly enter macrophages and in a couple of days develop morphologically distinct granulomas. We have now combined the use of red BCG in macrophages and red M.marinum in the fish with subsequently administered, green dye-labeled PLGA NPs enclosing rifampicin. In this presentation I will summarize the recent success of our group with our collaborators.
Hans Petter Kleppen, UMB Ås:
"Bacteriophages infecting lactic acid bacteria of milk fermentation", and below is an abstract.
Abstract:
Industrial food fermentations by lactic acid bacteria (LAB) are of great practical and economic importance. Bacteriophages (phages; bacterial viruses) infecting LAB can negatively affect quality, safety and value of the fermented product. This problem is especially pronounced in the dairy industry, where bacteriophages are recognized as the most common cause of fermentation failure.
Here, we present a study on bacteriophages infecting Lactococcus lactis of starter cultures used in the production of Dutch-type cheese. Virulent bacteriophages were identified as the predominant phage group, and not prophages naturally carried by starter culture LAB. Bacteriophage biodiversity was assessed by DNA sequencing and a growth inhibition assay employing arrays of starter culture isolates as indicators. Large day-to-day variation in diversity was found within a dairy plant and a peak in the biodiversity coincided with a fermentation failure. The effect of starter culture rotation was reflected by a radical change in phage diversity, but phages infecting the original starter culture rapidly re-emerged. Phage levels in raw milk were low and the phage contamination most probably came from within the plant.
A new bacteriophage, phiLmd1, represents the first dairy Leuconostoc phage to be characterized on a genomic level. It showed resistance to pasteurization and was able to infect bacteria of 3 of the 4 commercial starter cultures tested. Its 26.2 kb genome was similar to that of a Leuconostoc phage of vegetable origin but not to those of dairy phages infecting Lactococcus.
This study has provided deeper understanding of how bacteriophages affect the production of Dutch-type cheese in Norway. Determination of high phage quantities and diversities in the dairy environment and during milk fermentations stresses the importance of stringent hygiene measures, protection of bulk starter milk from contaminating phage and the use of phage-unrelated starter cultures in starter culture rotation. The knowledge gained in this study may also be useful for other industrial fermentations.
Previous meetings:
BIG foredrag 17. Januar 2013
Time: 15:15 Venue: Auditorium 2, Biology building (Blindernveien 31)
Tittel: Enzymatic conversion of biomass - from discovery, via basic science to application
(The talk will have a particular focus on the last part of the abstract)
The basis for a bio-economy lies in the development of a biorefining industry enabled by enzyme tools that are tailored for available biomass and business opportunities. In the new NorZymeD project (Biotek 2021) we will focus on developing enzymes and processes for biomasses and value chains where Norway has clear competitive advantages, namely lignocellulosics and marine co-products from fisheries and aquaculture. Starting at unique biodiversities of the arctic, hot vents and gut microbiomes, the project will build generic competence by establishing a national "enzyme development pipeline". Through national complementarity and distribution of tasks, we will combine expertise on thermophilic enzymes in Bergen and cold-adapted enzymes in Tromsø, with expertise in enzyme engineering and applied enzymology in Ås, fermentation and screening facilities at SINTEF, and structural characterization in Tromsø. One innovative aim is to combine the best of cold- and heat-adapted enzymes using bioinformatics, protein engineering and gene shuffling-based directed evolution. Fundamental enzyme work will include in-depth studies of enzyme systems for the conversion of cellulose and related recalcitrant polysaccharides. This part of the project, to which most of the presentation will be dedicated, includes metagenomics of cellulose-converting microbial communities (1), enzyme discovery (2-5), and fundamental structure-function studies of relevant enzymes (6,7).
1. Metagenomics of the Svalbard reindeer rumen microbiome reveals abundance of polysaccharide utilization loci. Pope PB, Mackenzie AK, Gregor I, Smith W, Sundset MA, McHardy AC, Morrison M, Eijsink VG. PLoS One. 2012;7(6):e38571
2. An oxidative enzyme boosting the enzymatic conversion of recalcitrant polysaccharides. Vaaje-Kolstad G, Westereng B, Horn SJ, Liu Z, Zhai H, Sørlie M, Eijsink VG. Science. 2010 Oct 8;330(6001):219-22
3. The putative endoglucanase PcGH61D from Phanerochaete chrysosporium is a metal-dependent oxidative enzyme that cleaves cellulose. Westereng B, Ishida T, Vaaje-Kolstad G, Wu M, Eijsink VG, Igarashi K, Samejima M, Ståhlberg J, Horn SJ, Sandgren M. PLoS One. 2011;6(11):e27807.
4.Cleavage of cellulose by a CBM33 protein. Forsberg Z, Vaaje-Kolstad G, Westereng B, Bunæs AC, Stenstrøm Y, MacKenzie A, Sørlie M, Horn SJ, Eijsink VG. Protein Sci. 2011 Sep;20(9):1479-83.
6. Novel enzymes for the degradation of cellulose; Horn SJ, Vaaje-Kolstad G, Westereng B, Eijsink VG; Biotechnol Biofuels. 2012 Jul 2;5(1):45.
6. Hallmarks of processivity in glycoside hydrolases from crystallographic and computational studies of the Serratia marcescens chitinases. Payne CM, Baban J, Horn SJ, Backe PH, Arvai AS, Dalhus B, Bjørås M, Eijsink VG, Sørlie M, Beckham GT, Vaaje-Kolstad G. J Biol Chem. 2012 Oct 19;287(43):36322-30.
7. NMR structure of a lytic polysaccharide monooxygenase provides insight into copper binding, protein dynamics, and substrate interactions. Aachmann FL, Sørlie M, Skjåk-Bræk G, Eijsink VG, Vaaje-Kolstad G. Proc Natl Acad Sci U S A. 2012 Nov 13;109(46):18779-84
Full list of BIG Oslo fall 2012 events (pdf)
11. October: "NMR structure determination to study protein-carbohydrate recognition processes and a novel bacterial N-glycosylation system"
Dr. Mario Schubert, Institute of Molecular Biology and Biophysics, ETH Zürich. Dr. Schubert will tell us about the protein-carbohydrate interaction of a novel fungal defense lectin, and how this interaction is utilized as a defense mechanism in different organisms. Knowledge of the structural basis for such protein-carbohydrate interactions is essential to understand host-pathogen interactions and biological defense systems. Dr. Schubert started out working with biomolecular NMR during his PhD, but he has got increasingly interested in glycobiology. He will also present recent work, done together with collaborators at ETH, characterizing transferases involved in a novel type of N-linked glycosylation found in pathogenic bacteria.
Time: 15:15 Venue: Auditorium 2, Biology building (Blindernveien 31)
25. October: "The hyperthermophilic Archaea Ignicoccus hospitalis and Nanoarchaeum equitans: Unusual prokaryotic cells with high structural complexity"
Prof. Dr. Reinhard Rachel, Centre for EM / Anatomy at the Faculty of Biology & Preclin. Med., University of Regensburg. Dr. Rachel will tell us a fascinating story of how I. hostpitalis and N. equitans co-exist in a unique archaeal biocoenosis. N. equitans are dependent on co-cultivation with I.hostpitalis. The special relationship between the organisms is reflected in the original and complex organization of several metabolic processes.
Time: 15:15 Venue: Auditorium 2, Biology building (Blindernveien 31)
1. November: "The roles of glycans in human disease"
Dr. Gerald Hart, DeLamar Professor and Director of Biological Chemistry, Johns Hopkins University School of Medicine. Dr. Hart and his team were the first to describe the novel concept of glycosylation of cytoplasmatic and nuclear proteins by addition of a single N-acetylglucosamin (GlcNAc) to a serine or threonine, O-linked GlcNAcylation. Since then his team has developed necessary tools to study GlcNacylation and applied them to elucidate the biological functions of this post translational modification (PTM). O-linked GlcNacylation plays an important role in regulating cellular functions, analogous to other PTMs such as phosphorylation, and is involved in several diseases, such as neurodegenerative disease, cancer and diabetes.
Time: 15:15 Venue: Auditorium 2, Biology building (Blindernveien 31)
8. November: "Can You Change Your Genes?"
Tim Spector, professor of genetic epidemiology, King’s College London, will present his research and ideas on how life experience and epigenetics influence our genes and genetic inheritance. He initiated the twin project, TwinsUK, originally focusing on inheritance and rheumatologic diseases, which has expanded into several other research areas. Among these, is the EpiTwin project aiming to understand how epigenetic variation between twins relates to different susceptibility to disease. He has recently published the book: “Identically Different: why you can change your genes.” The public lecture is hosted in association with Oslo Epigenetics Symposium, and will be followed by a scientific debate.
Time: 19:00 Venue: House of Literature (Wergelandsveien 29, city centre)
17. September: "Nanomedicine for drug delivery across biological barriers: intestines, skin and lung"
Prof. Dr. Claus-Michael Lehr, professor at Saarland University, and also cofounder and head of the department “Drug Delivery” of the recently established Helmholtz Institute for Pharmaceutical Research Saarland. His research explores biological barriers, in particular the gastro-intestinal tract, the skin and the lungs, and he is engaged in developing the appropriate carriers capable of crossing these epithelial barriers to deliver active molecules to their target. He will present new in-vitro models to test drug delivery and nano-scale drug carrying systems.
Time: 15:15 Venue: Auditorium 2, Biology building (Blindernveien 31)
16. August: "High sensitivity, automation and selectivity in analytical biochemistry"
Assoc. Prof. Steven Wilson from Bioanalytics@uio, part of the Department of Chemistry, UiO, will present their research developing and applying innovative methods for detection and structure determination of drugs, naturally occurring biomolecules/biomarkers and environmental biomarkers. A goal for the talk is to give you some ideas on how to overcome analytical challenges in your own research.
Time: 15:15 Venue: Auditorium 2, Biology building (Blindernveien 31)
May 10th: Jonathan Hodkin fra Oxford University som vil presentere sine studier av immunitet og utviklingsbiologi I modellorganismen Caenorhabditis elegans
May 22th: Annemarie Meijer fra Universitetet i Leiden vil holde et foredrag med tittel “Zebrafish as a model for mycobacterium infection and high-throughput
anti-tuberculosis drug screening”
Garreth Griffiths fra Universitetet i Oslo (IMBV) vil holde foredrag med følgende tittel “Nanoparticle-based therapies against tuberculosis in the zebrafish model”
Robert Lyle
Title: "Extensive variation and low heritability of DNA methylation identified in a twin study"
Date: 25th January 2012
Vessela N Kristensen
Title: "Pathway-based modeling for prediction of treatment response and survival in breast cancer"
Date: 14th March
Jan Terje Andersen
from the Centre for Immune Regulation (CIR), Department of Immunology, Oslo University Hospital.
Title: "The (not so) neonatal Fc receptor (FcRn):
From basic molecular mechanisms to design of next-generation therapeutics."
Abstract
Date: Wednesday 14th December, 2011
Venue: Auditorium 2, Kristine Bonnevies Hus (Biologibygningen)
Time: 14:15-15:00.
Refreshments from 14:00.
Kjetil Jakobsen
Centre for Ecological and Evolutionary Synthesis (CEES), Dept. of Biology, UiO
Title: "High throughput sequencing of the Atlantic cod genome reveals a unique immune system."
Abstract
Date: Thursday 1th of December, 2011
Venue: Auditorium 2, Kristine Bonnevies hus (Biologibygningen)
Time: 13:00-13:45
Refreshments from 12:45
Guest lecture by Anne Spurkland
Institute of Basic Medical Sciences, UiO
Title: "Genetic analysis implicates a primary role for immune mechanisms in the pathogenesis of multiple sclerosis"
Abstract
Date: Wednesday 26th of October, 2011
Venue: Store Auditorium, Domus Medica (Gaustad)
Time: 14:15-15:30
Refreshments from 14:00
Guest lecture by Patrick Couvreur
Université Paris-Sud, France
Title: "Nanomedicines: a new approach for the treatment of severe diseases"
Abstract
Date: Friday 26th of August, 2011
Venue: Auditorium 1, Kristine Bonnevies hus (Biologibygningen)
Time: 14:45-15:30
Refreshments from 14:30
