Selected publications

07.06.2019

Current researches and discoveries of our scientists


The structure and function of Iristatin, a novel immunosuppressive tick salivary cystatin

To successfully feed, ticks inject pharmacoactive molecules into the vertebrate host including cystatin cysteine protease inhibitors. However, the molecular and cellular events modulated by tick saliva remain largely unknown. Here, we describe and characterize a novel immunomodulatory cystatin, Iristatin, which is upregulated in the salivary glands of feeding Ixodes ricinus ticks. We present the crystal structure of Iristatin at 1.76 Å resolution. Purified recombinant Iristatin inhibited the proteolytic activity of cathepsins L and C and diminished IL-2, IL-4, IL-9, and IFN-γ production by different T-cell populations, IL-6 and IL-9 production by mast cells, and nitric oxide production by macrophages. Furthermore, Iristatin inhibited OVA antigen-induced CD4+ T-cell proliferation and leukocyte recruitment in vivo and in vitro. Our results indicate that Iristatin affects wide range of anti-tick immune responses in the vertebrate host and may be exploitable as an immunotherapeutic.

Kotál, J., Stergiou, N., Buša, M., Chlastáková. A.Beránková, Z., Řezáčová, P., Langhansová, H., Schwarz, A., Calvo, E., Kopecký, J., Mareš, M., Schmitt, E., Chmelař, J., Kotsyfakis, M. 2019. The structure and function of Iristatin, a novel immunosuppressive tick salivary cystatin. Cellular and Molecular Life Sciences 76: 2003–2013.

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Biosynthesis of the neurotoxin domoic acid in a bloom-forming diatom

Oceanic harmful algal blooms of Pseudo-nitzschia diatoms produce the potent mammalian neurotoxin domoic acid (DA). Despite decades of research, the molecular basis for its biosynthesis is not known. By using growth conditions known to induce DA production in Pseudo-nitzschia multiseries, we implemented transcriptome sequencing in order to identify DA biosynthesis genes that colocalize in a genomic four-gene cluster. We biochemically investigated the recombinant DA biosynthetic enzymes and linked their mechanisms to the construction of DA’s diagnostic pyrrolidine skeleton, establishing a model for DA biosynthesis. Knowledge of the genetic basis for toxin production provides an orthogonal approach to bloom monitoring and enables study of environmental factors that drive oceanic DA production.

Brunson, J. K., McKinnie, S. M. K., Chekan, J. R., McCrow, J. P., Miles, Z. D., Bertrand, E. M., Bielinski, V. A., Luhavaya, H., Oborník, M., Smith, G. J., Hutchins, D. A., Allen, A. E., Moore, B. S. 2018. Biosynthesis of the neurotoxin domoic acid in a bloom-forming diatom. Science 361: 1356–1358.

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Spatial Variability of Antarctic Surface Snow Bacterial Communities

It was once a long-held view that the Antarctic was a pristine environment with low biomass, low biodiversity and low rates of microbial activity. However, as the intensity of scientific investigation has increased, so these views have started to change. In particular, the role and impact of human activity toward indigenous microbial communities has started to come under more intense scrutiny. During the Subglacial Lake Ellsworth exploration campaign in December 2012, a microbiological survey was conducted to determine the extent and likelihood of exogenous input into the subglacial lake system during the hot-water drilling process. Snow was collected from the surface to represent that used for melt water production for hot-water drilling. The results of this study showed that snow used to provide melt water differed in its microbiological composition from that of the surrounding area and raised the question of how the biogeography of snow-borne microorganisms might influence the potential outcome of scientific analyses. In this study, we investigated the biogeography of microorganisms in snow around a series of Antarctic logistic hubs, where human activity was clearly apparent, and from which scientific investigations have been undertaken. A change in microbial community structure with geographical location was apparent and, notably, a decrease in alpha diversity at more remote southern latitudes. Soil-related microorganisms dominated microbial assemblages suggesting terrestrial input, most likely from long-range aeolian transport into continental Antarctica. We also observed that relic DNA was not a major issue when assessing snow samples. Overall, our observations might have profound implications for future scientific activities in Antarctica, such as the need to establish “no-go” protected areas, the need for better characterization of field sites and improved protocols for sterilization and verification of ice drilling equipment.

Mallard, L. A., Šabacká, M., Magiopoulos, I., Mowlem, M., Hodson, A., Tranter, M., Siegert, M. J., Pearce, D. A. Spatial Variability of Antarctic Surface Snow Bacterial Communities. Frontiers in Microbiology 10: 461.

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Explaining marriage patterns in a globally representative sample through socio-ecology and population history: A Bayesian phylogenetic analysis using a new supertree

Comparative analyses have sought to explain variation in human marriage patterns, often using predictions derived from sexual selection theory. However, most previous studies have not controlled for non-independence of populations due to shared ancestry. Here we leverage a phylogenetic supertree of human populations that includes all 186 populations in the Standard Cross-Cultural Sample (SCCS), a globally representative and widely-used sample of human populations. This represents the most comprehensive human phylogeny to date, and allows us not only to control for non-independence, but also to quantify the role of population history in explaining behavioral variation, in addition to current socio-ecological conditions. We use multiple imputation to overcome missing data problems and build a comprehensive Bayesian phylogenetic model of marriage patterns with two correlated response variables and eleven minimally collinear predictors capturing various socio-ecological conditions. We show that ignoring phylogeny could lead to both false positives and false negatives, and that the phylogeny explained about twice as much variance as all the predictors combined. Pathogen stress and assault frequency emerged as the predictors most strongly associated with polygyny, which had been considered evidence for female choice of good genes and male intra-sexual competition or male coercion, respectively. Mixed support was found for a polygyny threshold based on variance in male wealth, which is discussed in light of recent theory. Barring caveats, these findings refine our understanding of the evolution of human marriage systems, and highlight the value of combining population history and current socio-ecology in explaining human behavioral variation. Future studies using the SCCS should do so using the present supertree.

Minocher, R., Duda, P., Jaeggi, A. V. 2019. Explaining marriage patterns in a globally representative sample through socio-ecology and population history: A Bayesian phylogenetic analysis using a new supertree. Evolution and Human Behavior 40: 176-187.

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Additional row of outer hair cells – The unique pattern of the Corti organ in a subterranean rodent, the Gansu zokor (Eospalax cansus)

Acoustic conditions in burrows are different from those aboveground and restrict hearing of subterranean mammals to low frequencies, which is reflected in the earmorphology. While low-frequency adaptations of the middle ear attracted more attention of researches, the inner ear remained rather understudied. Here, we examined the cochlea of the inner ear of the Gansu zokor (Eospalax cansus), a subterranean rodent from the Tibetan Plateau. We focused on the quantitative parameters of the organ of Corti, which are assumed to determine hearing sensitivity and frequency tuning. Apart from the morphological traits common to the ear of subterranean rodents studied thus far, the Gansu zokor shows two unique features: the presence of a fourth row of outer hair cells along 20% to 50% of the basilar membrane length and almost constant width of the organ of Corti over more than 10% of its spiral length. Both these anomalies occur in the middle of the cochlear spiral. These features are unusual in comparative morphology of the organ of Corti and presumably are reflected in the functional specialization. They are expected to affect sensitivity and /or resolution of hearing in the frequency rangeregistered in the given cochlear segment. The Gansu zokor thus profiles to an interesting candidate for hearing research which might provide further insight not only into morpho-functional adaptations in subterranean mammals in particular but also in the function of outer hair cells in general.

Pleštilová, L.Hrouzková, E., Burda, H., Hua, L., Šumbera, R. 2019. Additional row of outer hair cells – The unique pattern of the Corti organ in a subterranean rodent, the Gansu zokor (Eospalax cansus). Mammalian Biology 94: 11–17.

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Recent advances in trypanosomatid research: genome organization, expression, metabolism, taxonomy and evolution.

Unicellular flagellates of the family Trypanosomatidae are obligatory parasites of invertebrates, vertebrates and plants. Dixenous species are aetiological agents of a number of diseases in humans, domestic animals and plants. Their monoxenous relatives are restricted to insects. Because of the high biological diversity, adaptability to dramatically different environmental conditions, and omnipresence, these protists have major impact on all biotic communities that still needs to be fully elucidated. In addition, as these organisms represent a highly divergent evolutionary lineage, they are strikingly different from the common 'model system' eukaryotes, such as some mammals, plants or fungi. A number of excellent reviews, published over the past decade, were dedicated to specialized topics from the areas of trypanosomatid molecular and cell biology, biochemistry, host-parasite relationships or other aspects of these fascinating organisms. However, there is a need for a more comprehensive review that summarizing recent advances in the studies of trypanosomatids in the last 30 years, a task, which we tried to accomplish with the current paper.

Maslov, D. A., Opperdoes, F. R., Kostygov, A. Y., Hashimi, H.Lukeš, J., Yurchenko, V. 2019. Recent advances in trypanosomatid research: genome organization, expression, metabolism, taxonomy and evolution. Parasitology 219: 1–27.

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