The NCCR TransCure: An Incubator for Interdisciplinary Research.

The National Center of Competence in Research (NCCR) TransCure, funded by the Swiss National Science Foundation and the University of Bern, was active from 2010 to 2022. It provided unique research and educational framework in the membrane transporter and ion channel field. Thanks to an interdisciplinary approach comprising physiology, structural biology, and chemistry, in parallel to a rich offer in complementary areas such as education and technology transfer, the network achieved outstanding scientific results and contributed to the education of young scientists. In this review, we present the main features and milestones of the NCCR TransCure.

Vitaport: A Learning and Artistic Path for Public Outreach on Transporter Biology, Health and Drug Discovery.

In occasion of its conclusion, the National Center of Competence in Research (NCCR) TransCure launched a temporary learning and artistic path in the city of Bern named 'Vitaport - Was unser Körper transportiert'. The path explained how nutrients are transported through our body and how molecules find their way to the right organ to achieve their effect there. NCCR TransCure researchers, together with students of the Bern School of Design, developed ceramic objects, texts and information graphics that took the public on a multidisciplinary journey of discovery through the human body. In this article, we report about aims, development, challenges and outcome of this ambitious science outreach project in which we could experience a rewarding and successful collaboration between scientists and artists.

Differences in cell division rates drive the evolution of terminal differentiation in microbes.

Multicellular differentiated organisms are composed of cells that begin by developing from a single pluripotent germ cell. In many organisms, a proportion of cells differentiate into specialized somatic cells. Whether these cells lose their pluripotency or are able to reverse their differentiated state has important consequences. Reversibly differentiated cells can potentially regenerate parts of an organism and allow reproduction through fragmentation. In many organisms, however, somatic differentiation is terminal, thereby restricting the developmental paths to reproduction. The reason why terminal differentiation is a common developmental strategy remains unexplored. To understand the conditions that affect the evolution of terminal versus reversible differentiation, we developed a computational model inspired by differentiating cyanobacteria. We simulated the evolution of a population of two cell types -nitrogen fixing or photosynthetic- that exchange resources. The traits that control differentiation rates between cell types are allowed to evolve in the model. Although the topology of cell interactions and differentiation costs play a role in the evolution of terminal and reversible differentiation, the most important factor is the difference in division rates between cell types. Faster dividing cells always evolve to become the germ line. Our results explain why most multicellular differentiated cyanobacteria have terminally differentiated cells, while some have reversibly differentiated cells. We further observed that symbioses involving two cooperating lineages can evolve under conditions where aggregate size, connectivity, and differentiation costs are high. This may explain why plants engage in symbiotic interactions with diazotrophic bacteria.

Advantages of the division of labour for the long-term population dynamics of cyanobacteria at different latitudes.

A fundamental advancement in the evolution of complexity is division of labour. This implies a partition of tasks among cells, either spatially through cellular differentiation, or temporally via a circadian rhythm. Cyanobacteria often employ either spatial differentiation or a circadian rhythm in order to separate the chemically incompatible processes of nitrogen fixation and photosynthesis. We present a theoretical framework to assess the advantages in terms of biomass production and population size for three species types: terminally differentiated (heterocystous), circadian, and an idealized species in which nitrogen and carbon fixation occur without biochemical constraints. On the basis of real solar irradiance data at different latitudes, we simulate population dynamics in isolation and in competition for light over a period of 40 years. Our results show that in isolation and regardless of latitude, the biomass of heterocystous cyanobacteria that optimally invest resources is comparable to that of the idealized unconstrained species. Hence, spatial division of labour overcomes biochemical constraints and enhances biomass production. In the circadian case, the strict temporal task separation modelled here hinders high biomass production in comparison with the heterocystous species. However, circadian species are found to be successful in competition for light whenever their resource investment prevents a waste of fixed nitrogen more effectively than do heterocystous species. In addition, we show the existence of a trade-off between population size and biomass accumulation, whereby each species can optimally invest resources to be proficient in biomass production or population growth, but not necessarily both. Finally, the model produces chaotic dynamics for population size, which is relevant to the study of cyanobacterial blooms.

Effects of fertilisation on grass and forb gamic reproduction in semi-natural grasslands.

Studying the effects of fertilisation on the seed production of grassland species can help understand the vegetation changes and biodiversity losses due to soil eutrophication. The seed production of fifteen grasses and seventeen forbs from a temperate hay meadow was studied under three fertilisation treatments: 0-0-0, 0-54-108 and 192-108-216 kg N, P2O5 and K2O respectively, per year. Fertile shoots collected at the seed maturation stage were analysed for all main traits of the gamic reproduction. On average, forbs produced more ovules and viable seeds per shoot (199 and 65, respectively) than grasses (112 and 35, respectively). Fertilisation increased the number of inflorescences per shoot in both grasses and forbs and had a limited but variable effect on germinability and viability in the two functional groups: viability increased in grasses but often decreased in forbs. This pattern resulted in 55% and 11% increases in viable seed production in grasses and forbs, respectively. At the higher level of fertilisation, shoot density was positively related to the number of viable seeds per shoot in grasses and to the seed size in forbs. These results highlight that the traits of the gamic reproduction can contribute to explain the relationship between soil nutrient richness and grassland species composition and richness.

The evolutionary path to terminal differentiation and division of labor in cyanobacteria.

A common trait often associated with multicellularity is cellular differentiation, which is a spatial separation of tasks through the division of labor. In principle, the division of labor does not necessarily have to be constrained to a multicellular setting. In this study, we focus on the possible evolutionary paths leading to terminal differentiation in cyanobacteria. We develop mathematical models for two developmental strategies. First, of populations of terminally differentiated single cells surviving by the exchange of common goods. Second, of populations exhibiting terminal differentiation in a multicellular setting. After testing the two strategies against the effect of disruptive mutations (i.e. "cheater" mutants), we assess the effects of selection on the optimization of the ratio of vegetative (carbon fixing) to heterocystous (nitrogen fixing) cells, which in turn leads to the maximization of the carrying capacity for the population density. In addition, we compare the performance of differentiated populations to undifferentiated ones that temporally separate tasks in accordance to a day/night cycle. We then compare some predictions of our model with phylogenetic relationships derived from analyzing 16S rRNA sequences of different cyanobacterial strains. In line with studies indicating that group or spatial structure are ways to evolve cooperation and protect against the spread of cheaters, our work shows that compartmentalization afforded by multicellularity is required to maintain the vegetative/heterocyst division in cyanobacteria. We find that multicellularity allows for selection to optimize the carrying capacity. These results and the phylogenetic analysis indicates that terminally differentiated cyanobacteria evolved after undifferentiated species. In addition, we show that, in regimes of short daylight periods, terminally differentiated species perform worse than undifferentiated species that follow the day/night cycle; indicating that undifferentiated species have an evolutionary advantage in regimes of short daylight periods.

Phenotypic diversity of multicellular filamentation in oral Streptococci.

Filamentous multicellular bacteria are among the most ancient multicellular organisms. They inhabit a great variety of environments and are present in the human body, including the oral cavity. Beside the selective advantages related to the larger size achieved through filamentation, the development of multicellular bacteria can be also driven by simple ecological factors such as birth and death rates at the cellular level. In order to extend earlier results obtained in aquatic species, we investigate the filamentation process of four different strains of oral streptococci, namely S. mutans, S. salivarius, S. oralis and S. anginosus. The results indicate differences in the capacities of different streptococcus species to form filaments, manifested in terms of length and the time-scale of filament elongation. The filamentation pattern of these oral streptococci resembles that of aquatic bacteria, whereby filaments reach a peak length during exponential growth and become short when the population reaches a steady state. Hence, this study validates that multicellularity can be an emergent property of filamentous bacteria of different ecological niches, and that phenotypic differences in filamentation can occur within species of the same genus, in this case oral streptococci. Moreover, given the role that specific oral streptococci can play in the etiology of oral diseases, these results can possibly open new perspectives in the study of the virulence properties of these species.

Correction: Use of a Four-Tiered Graph to Parse the Factors Leading to Phenotypic Clustering in Bacteria: A Case Study Based on Samples from the Aletsch Glacier.

[This corrects the article on p. e65059 in vol. 8.].

Use of a four-tiered graph to parse the factors leading to phenotypic clustering in bacteria: a case study based on samples from the Aletsch Glacier.

An understanding of bacterial diversity and evolution in any environment requires knowledge of phenotypic diversity. In this study, the underlying factors leading to phenotypic clustering were analyzed and interpreted using a novel approach based on a four-tiered graph. Bacterial isolates were organized into equivalence classes based on their phenotypic profile. Likewise, phenotypes were organized in equivalence classes based on the bacteria that manifest them. The linking of these equivalence classes in a four-tiered graph allowed for a quick visual identification of the phenotypic measurements leading to the clustering patterns deduced from principal component analyses. For evaluation of the method, we investigated phenotypic variation in enzyme production and carbon assimilation of members of the genera Pseudomonas and Serratia, isolated from the Aletsch Glacier in Switzerland. The analysis indicates that the genera isolated produce at least six common enzymes and can exploit a wide range of carbon resources, though some specialist species within the pseudomonads were also observed. We further found that pairwise distances between enzyme profiles strongly correlate with distances based on carbon profiles. However, phenotypic distances weakly correlate with phylogenetic distances. The method developed in this study facilitates a more comprehensive understanding of phenotypic clustering than what would be deduced from principal component analysis alone.

Emergent multicellular life cycles in filamentous bacteria owing to density-dependent population dynamics.

Filamentous bacteria are the oldest and simplest known multicellular life forms. By using computer simulations and experiments that address cell division in a filamentous context, we investigate some of the ecological factors that can lead to the emergence of a multicellular life cycle in filamentous life forms. The model predicts that if cell division and death rates are dependent on the density of cells in a population, a predictable cycle between short and long filament lengths is produced. During exponential growth, there will be a predominance of multicellular filaments, while at carrying capacity, the population converges to a predominance of short filaments and single cells. Model predictions are experimentally tested and confirmed in cultures of heterotrophic and phototrophic bacterial species. Furthermore, by developing a formulation of generation time in bacterial populations, it is shown that changes in generation time can alter length distributions. The theory predicts that given the same population growth curve and fitness, species with longer generation times have longer filaments during comparable population growth phases. Characterization of the environmental dependence of morphological properties such as length, and the number of cells per filament, helps in understanding the pre-existing conditions for the evolution of developmental cycles in simple multicellular organisms. Moreover, the theoretical prediction that strains with the same fitness can exhibit different lengths at comparable growth phases has important implications. It demonstrates that differences in fitness attributed to morphology are not the sole explanation for the evolution of life cycles dominated by multicellularity.