@article{1571, abstract = {Epistatic interactions can frustrate and shape evolutionary change. Indeed, phenotypes may fail to evolve when essential mutations are only accessible through positive selection if they are fixed simultaneously. How environmental variability affects such constraints is poorly understood. Here, we studied genetic constraints in fixed and fluctuating environments using the Escherichia coli lac operon as a model system for genotype-environment interactions. We found that, in different fixed environments, all trajectories that were reconstructed by applying point mutations within the transcription factor-operator interface became trapped at suboptima, where no additional improvements were possible. Paradoxically, repeated switching between these same environments allows unconstrained adaptation by continuous improvements. This evolutionary mode is explained by pervasive cross-environmental tradeoffs that reposition the peaks in such a way that trapped genotypes can repeatedly climb ascending slopes and hence, escape adaptive stasis. Using a Markov approach, we developed a mathematical framework to quantify the landscape-crossing rates and show that this ratchet-like adaptive mechanism is robust in a wide spectrum of fluctuating environments. Overall, this study shows that genetic constraints can be overcome by environmental change and that crossenvironmental tradeoffs do not necessarily impede but also, can facilitate adaptive evolution. Because tradeoffs and environmental variability are ubiquitous in nature, we speculate this evolutionary mode to be of general relevance.}, author = {De Vos, Marjon and Dawid, Alexandre and Šunderlíková, Vanda and Tans, Sander}, journal = {PNAS}, number = {48}, pages = {14906 -- 14911}, publisher = {National Academy of Sciences}, title = {{Breaking evolutionary constraint with a tradeoff ratchet}}, doi = {10.1073/pnas.1510282112}, volume = {112}, year = {2015}, } @article{1581, abstract = {In animal embryos, morphogen gradients determine tissue patterning and morphogenesis. Shyer et al. provide evidence that, during vertebrate gut formation, tissue folding generates graded activity of signals required for subsequent steps of gut growth and differentiation, thereby revealing an intriguing link between tissue morphogenesis and morphogen gradient formation.}, author = {Bollenbach, Mark Tobias and Heisenberg, Carl-Philipp J}, journal = {Cell}, number = {3}, pages = {431 -- 432}, publisher = {Cell Press}, title = {{Gradients are shaping up}}, doi = {10.1016/j.cell.2015.04.009}, volume = {161}, year = {2015}, } @article{1586, abstract = {Through metabolic engineering cyanobacteria can be employed in biotechnology. Combining the capacity for oxygenic photosynthesis and carbon fixation with an engineered metabolic pathway allows carbon-based product formation from CO2, light, and water directly. Such cyanobacterial 'cell factories' are constructed to produce biofuels, bioplastics, and commodity chemicals. Efforts of metabolic engineers and synthetic biologists allow the modification of the intermediary metabolism at various branching points, expanding the product range. The new biosynthesis routes 'tap' the metabolism ever more efficiently, particularly through the engineering of driving forces and utilization of cofactors generated during the light reactions of photosynthesis, resulting in higher product titers. High rates of carbon rechanneling ultimately allow an almost-complete allocation of fixed carbon to product above biomass.}, author = {Angermayr, Andreas and Gorchs, Aleix and Hellingwerf, Klaas}, journal = {Trends in Biotechnology}, number = {6}, pages = {352 -- 361}, publisher = {Elsevier}, title = {{Metabolic engineering of cyanobacteria for the synthesis of commodity products}}, doi = {10.1016/j.tibtech.2015.03.009}, volume = {33}, year = {2015}, } @article{1623, abstract = {Background Photosynthetic cyanobacteria are attractive for a range of biotechnological applications including biofuel production. However, due to slow growth, screening of mutant libraries using microtiter plates is not feasible. Results We present a method for high-throughput, single-cell analysis and sorting of genetically engineered l-lactate-producing strains of Synechocystis sp. PCC6803. A microfluidic device is used to encapsulate single cells in picoliter droplets, assay the droplets for l-lactate production, and sort strains with high productivity. We demonstrate the separation of low- and high-producing reference strains, as well as enrichment of a more productive l-lactate-synthesizing population after UV-induced mutagenesis. The droplet platform also revealed population heterogeneity in photosynthetic growth and lactate production, as well as the presence of metabolically stalled cells. Conclusions The workflow will facilitate metabolic engineering and directed evolution studies and will be useful in studies of cyanobacteria biochemistry and physiology. }, author = {Hammar, Petter and Angermayr, Andreas and Sjostrom, Staffan and Van Der Meer, Josefin and Hellingwerf, Klaas and Hudson, Elton and Joensson, Hakaan}, journal = {Biotechnology for Biofuels}, number = {1}, publisher = {BioMed Central}, title = {{Single-cell screening of photosynthetic growth and lactate production by cyanobacteria}}, doi = {10.1186/s13068-015-0380-2}, volume = {8}, year = {2015}, } @article{1810, abstract = {Combining antibiotics is a promising strategy for increasing treatment efficacy and for controlling resistance evolution. When drugs are combined, their effects on cells may be amplified or weakened, that is the drugs may show synergistic or antagonistic interactions. Recent work revealed the underlying mechanisms of such drug interactions by elucidating the drugs'; joint effects on cell physiology. Moreover, new treatment strategies that use drug combinations to exploit evolutionary tradeoffs were shown to affect the rate of resistance evolution in predictable ways. High throughput studies have further identified drug candidates based on their interactions with established antibiotics and general principles that enable the prediction of drug interactions were suggested. Overall, the conceptual and technical foundation for the rational design of potent drug combinations is rapidly developing.}, author = {Bollenbach, Mark Tobias}, journal = {Current Opinion in Microbiology}, pages = {1 -- 9}, publisher = {Elsevier}, title = {{Antimicrobial interactions: Mechanisms and implications for drug discovery and resistance evolution}}, doi = {10.1016/j.mib.2015.05.008}, volume = {27}, year = {2015}, }