Biology subjects

Olsson, S.

Publications and source records attributed to Olsson, S..

25 records · Page 2Linked to original sources

bioRxiv2020

Discovery of a hidden transient state in all bromodomain families

Bromodomains (BDs) are small protein modules that interact with acetylated marks in histones. These post-translational modifications are pivotal to regulate gene expression, making BDs promising targets to treat several diseases. While the general structure of BDs is well known, their dynamical features and their interplay with other macromolecules are poorly understood, hampering the rational design of potent and selective inhibitors. Here we combine extensive molecular dynamics simulations, Markov state modeling and structural data to reveal a novel and transiently formed state that is conserved across all BD families. It involves the breaking of two backbone hydrogen bonds that anchor the ZA-loop with the A helix, opening a cryptic pocket that partially occludes the one associated with histone binding. Our results suggest that this novel state is an allosteric regulatory switch for BDs, potentially related to a recently unveiled BD-DNA binding mode.

biophysics↗

bioRxiv2020

OmicsDB::Pathogens - A database for exploring functional networks of plant pathogens

Plant pathogens are a great threat to food security. To combat them we need an understanding of how they work. Integrating large-scale omics datasets such as genomes and transcriptomes has been shown to provide deeper insights into many aspects of molecular biology. For a better understanding of plant pathogens, we aim to construct a platform for accessing genomic and gene co-expression networks for a range of pathogens and reference species. Currently we have integrated genomic and transcriptomics data from 10 species (Fusarium graminearum, Ustilago maydis, Blumeria graminis, Neurospora crassa, Schizosaccharomyces pombe, Saccharomyces cerevisiae, Escherichia coli, Arabidopsis thaliana, Mus musculus and Homo sapiens). Here we introduce OmicsDB::Pathogens (http://pathogens.omicsdb.org), a publicly available web portal with an underlying database containing genomic, and transcriptomic data and analysis tools. It allows non-bioinformaticians to browse genomic data and inspect and compare biological networks across species. The information is modelled in a graph-based database, enabling flexibility for querying and future extensions. Tools such as BLAST and Cytoscape.js are available together with the option of performing GO enrichment analysis. The database also enables the user to browse information such as Orthologs, Protein domains and publications citing a given gene. Herein we describe how to use this platform for generating hypotheses for the function of a gene. Availability and ImplementationCurrently, Omicsdb supports networks for 10 organisms and is freely available for public use at http://pathogens.omicsdb.org

microbiology↗

bioRxiv2019

Protein interactions of Magnaporthe oryzae protein kinase CK2 and secondary data analysis of a large number of transcriptomes suggest chaperone-like activity is integral to its function

CK2, a serine/threonine (S/T) kinase present in eukaryotic cells is known to have a vast number of substrates. We have recently shown that it localizes to nuclei and at pores between hyphal compartments in M. oryzae. We performed a pulldown-proteomics of M. oryzae CK2 catalytic subunit MoCKa to detect interacting proteins. The MoCKa pulldown was enriched for septa and nucleoli proteins and intrinsically disordered proteins (IDPs) containing a CK2 phosphorylation motif proposed to destabilize and unfold alpha helixes. This points to a function for CK2 phosphorylation and corresponding phosphatase dephosphorylation in the formation of functional protein-protein aggregates and protein-RNA/DNA binding. To test this as widely as possible we used secondary data downloaded from databases from a large range of M. oryzae experiments and also for a relatively closely related plant pathogenic fungus, Fusarium graminearum. We found that CKa expression was strongly positively correlated with S/T phosphatases as well as with disaggregase (HSP104, YDJ1, SSA1) and an autophagy indicating protein (ATG8). The latter points to increased protein aggregate formation at high levels of CKa expression. Our results suggest a general role for CK2 in aggregation and disaggregation of IDPs and their binding to proteins, DNA and RNA interactions.

cell biology↗

bioRxiv2019

Reckless driving: Improved phosphorous availability is a most likely important driver and species killer in angiosperm evolution

Introductory summarizing paragraphPlants show a large range of genome sizes with a more than thousand fold difference between the largest and the smallest genomes (Bennett, M. D., 1972; Bennett, 2005; Knight, 2005; Gregory et al., 2007; Bai et al., 2012; Kelly et al., 2015). Since, 1. DNA phosphorous is a phosphorous pool not possible to recycle within the cell. 2. Carnivorous plants with very small genomes living in low phosphorous environments uses carnivory to supply phosphorous (Leushkin et al., 2013). 3. The genus Fritillaria with very large genomes is dependent on mycorrhiza (Wang & Qiu, 2006; Kelly et al., 2015) probably mainly for supply of P, I decided to investigate if lifestyles connected with releases from P-limitation correlate with 1C-genome sizes. For the investigation I used available lifestyle data from several websites and articles (Wang & Qiu, 2006; Lysak et al., 2008) together with the Angiosperm C-values available at Kew http://data.kew.org/cvalues/. Based on this analysis I suggest the following order of P restriction for genome size expansions, from the least restricted to the most restricted, for the different lifestyles: Myco-heterotrophs<Parasitic plants<Mycorrhizal plants<Non-Mycorrhizal plants<Carnivorous plants. The data further suggest that a general improved P status most likely precedes whole genome duplication events and that uneven ploidy increases are more punishing than even ploidy most probably since uneven ploidy increases cannot be followed by adaptive recombination/selection. Thus P-limitation is a likely main restraint for angiosperm evolution and genome-expansion. However, relaxing this restraint leads plants into an evolutionary dead end with large nuclei (Bennetzen & Kellogg, 1997) and high P demand.

evolutionary biology↗

bioRxiv2018

Dynamic Graphical Models of Molecular Kinetics

Most current molecular dynamics simulation and analysis methods rely on the idea that the molecular system can be characterized by a single global state, e.g., a Markov State in a Markov State Model (MSM). In this approach, molecules can be extensively sampled and analyzed when they only possess a few metastable states, such as small to medium-sized proteins. However this approach breaks down in frustrated systems and in large protein assemblies, where the number of global meta-stable states may grow exponentially with the system size. Here, we introduce Dynamic Graphical Models (DGMs), which build upon the idea of Ising models, and describe molecules as assemblies of coupled subsystems. The switching of each sub-system state is only governed by the states of itself and its neighbors. DGMs need many fewer parameters than MSMs or other global-state models, in particular we do not need to observe all global system configurations to estimate them. Therefore, DGMs can predict new, previously unobserved, molecular configurations. Here, we demonstrate that DGMs can faithfully describe molecular thermodynamics and kinetics and predict previously unobserved metastable states for Ising models and protein simulations.

biophysics↗

bioRxiv2018

The effect of community dialogues and sensitization on patient reporting of adverse events in rural Uganda: uncontrolled before-after study

BackgroundThe patients that experience adverse events are in the best position to report them, only if they were empowered to do so. Systematic community engagement and support to patients in a rural setting to monitor any potential harm from medicines should provide evidence for patient safety.\n\nMethodsThis paper describes an uncontrolled before and after study aimed at assessing the effect of a community engagement strategy, the Community Dialogues and Sensitization (CDS) intervention between January and April 2017, on the knowledge, attitude and practice of reporting adverse drug events by community members in the two eastern Ugandan districts. A representative cross-sectional baseline household survey was done prior to the intervention in September 2016 (n=1034) and the end-line survey (n=827) in July 2017.\n\nResultsAfter implementation of the CDS intervention, there was an overall 20% (95% CI=16- 25) increase in awareness about adverse drug events in the community. The young people (15- 24 years) demonstrated a 41% (95% CI =31-52) increase and the un-educated showed a 50% (95% CI=37-63) increase in awareness about adverse drug events. The attitudes towards reporting increased overall by 5% in response to whether there was a need to report ADEs (95% CI =3-7). An overall 115% (95% CI =137-217) increase in the population that had ever experienced ADEs was also reported.\n\nConclusionOur evaluation shows that the CDS intervention increases knowledge, improves attitudes by catalyzing discussions among community members and health workers on health issues and monitoring safety of medicines.

scientific communication and education↗

bioRxiv2018

Localization and protein-protein interaction of protein kinase CK2 suggest a chaperone-like activity is integral to its function in M. oryzae.

Magnaporthe oryzae (Mo) is a model pathogen causing rice blast resulting in yield and economic losses world-wide. CK2 is a constitutively active, serine/threonine kinase in eukaryotes, having a wide array of known substrates and involved in many cellular processes. We investigated the localization and role of MoCK2 during growth and infection. BLAST search for MoCK2 components and targeted deletion of subunits was combined with protein-GFP fusions to investigate localization. We found one CKa and two CKb subunits of the CK2 holoenzyme. Deletion of the catalytic subunit CKa was not possible and might indicate that such deletions are lethal. The CKb subunits could be deleted but they were both necessary for normal growth and pathogenicity. Localization studies showed that the CK2 holoenzyme needed to be intact for normal localization at septal pores and at appressorium penetration pores. Nuclear localization of CKa was however not dependent on the intact CK2 holoenzyme. In appressoria, CK2 formed a large ring perpendicular to the penetration pore and the ring formation was dependent on the presence of all CK2 subunits. The effects on growth and pathogenicity of deletion of the b subunits combined with the localization indicate that CK2 can have important regulatory functions not only in the nucleus/nucleolus but also at fungal specific structures as septa and appressorial pores.

cell biology↗