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Michael Krogh Jensen

Bio: Michael Krogh Jensen is an academic researcher from Technical University of Denmark. The author has contributed to research in topics: CRISPR & Gene. The author has an hindex of 37, co-authored 91 publications receiving 4664 citations. Previous affiliations of Michael Krogh Jensen include Novo Nordisk Foundation & University of Copenhagen.
Topics: CRISPR, Gene, Cas9, Genome, Synthetic biology


Papers
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Journal ArticleDOI
TL;DR: The development and successful application of a multiplex CRISPR/Cas9 system for genome engineering of up to 5 different genomic loci in one transformation step in baker's yeast Saccharomyces cerevisiae is reported.

365 citations

Journal ArticleDOI
TL;DR: In silico analyses show that the NAC TRDs contain group-specific sequence motifs and are characterized by a high degree of intrinsic disorder, and demonstrate that the biochemical and functional specificity of NAC TFs is associated with both the DBDs and the TRDs.
Abstract: TFs (transcription factors) are modular proteins minimally containing a DBD (DNA-binding domain) and a TRD (transcription regulatory domain). NAC [for NAM (no apical meristem), ATAF, CUC (cup-shaped cotyledon)] proteins comprise one of the largest plant TF families. They are key regulators of stress perception and developmental programmes, and most share an N-terminal NAC domain. On the basis of analyses of gene expression data and the phylogeny of Arabidopsis thaliana NAC TFs we systematically decipher structural and functional specificities of the conserved NAC domains and the divergent C-termini. Nine of the ten NAC domains analysed bind a previously identified conserved DNA target sequence with a CGT[GA] core, although with different affinities. Likewise, all but one of the NAC proteins analysed is dependent on the C-terminal region for transactivational activity. In silico analyses show that the NAC TRDs contain group-specific sequence motifs and are characterized by a high degree of intrinsic disorder. Furthermore, ANAC019 was identified as a new positive regulator of ABA (abscisic acid) signalling, conferring ABA hypersensitivity when ectopically expressed in plants. Interestingly, ectopic expression of the ANAC019 DBD or TRD alone also resulted in ABA hypersensitivity. Expression of stress-responsive marker genes [COR47 (cold-responsive 47), RD29b (responsive-to-desiccation 29b) and ERD11 (early-responsive-to-dehydration 11)] were also induced by full-length and truncated ANAC019. Domain-swapping experiments were used to analyse the specificity of this function. Chimaeric proteins, where the NAC domain of ANAC019 was replaced with the analogous regions from other NAC TFs, also have the ability to positively regulate ABA signalling. In contrast, replacing the ANAC019 TRD with other TRDs abolished ANAC019-mediated ABA hypersensitivity. In conclusion, our results demonstrate that the biochemical and functional specificity of NAC TFs is associated with both the DBDs and the TRDs.

340 citations

Journal ArticleDOI
TL;DR: TF interaction partners such as E3 ubiquitin ligases and TF regions with ID represent future targets for engineering improved abiotic stress tolerance in crops and emerging gene regulatory networks based on TFs and their direct targets genes are presented.
Abstract: Transcription factors (TFs) are master regulators of abiotic stress responses in plants. This review focuses on TFs from seven major TF families, known to play functional roles in response to abiotic stresses, including drought, high salinity, high osmolarity, temperature extremes and the phytohormone ABA. Although ectopic expression of several TFs has improved abiotic stress tolerance in plants, fine-tuning of TF expression and protein levels remains a challenge to avoid crop yield loss. To further our understanding of TFs in abiotic stress responses, emerging gene regulatory networks based on TFs and their direct targets genes are presented. These revealed components shared between ABA-dependent and independent signaling as well as abiotic and biotic stress signaling. Protein structure analysis suggested that TFs hubs of large interactomes have extended regions with protein intrinsic disorder (ID), referring to their lack of fixed tertiary structures. ID is now an emerging topic in plant science. Furthermore, the importance of the ubiquitin-proteasome protein degradation systems and modification by sumoylation is also apparent from the interactomes. Therefore; TF interaction partners such as E3 ubiquitin ligases and TF regions with ID represent future targets for engineering improved abiotic stress tolerance in crops.

259 citations

Journal ArticleDOI
TL;DR: The data support a negative correlation between ABA levels and penetration resistance, and identify ATAF1 as a new stimuli-dependent attenuator of ABA signalling for the mediation of efficient penetration resistance in Arabidopsis upon Bgh attack.
Abstract: ATAF1 is a member of a largely uncharacterized plant-specific gene family encoding NAC transcription factors, and is induced in response to various abiotic and biotic stimuli in Arabidopsis thaliana. Previously, we showed that a mutant allele of ATAF1 compromises penetration resistance in Arabidopsis with respect to the non-host biotrophic pathogen Blumeria graminis f. sp. hordei (Bgh). In this study, we have used genome-wide transcript profiling to characterize signalling perturbations in ataf1 plants following Bgh inoculation. Comparative transcriptomic analyses identified an over-representation of abscisic acid (ABA)-responsive genes, including the ABA biosynthesis gene AAO3, which is significantly induced in ataf1 plants compared to wild-type plants following inoculation with Bgh. Additionally, we show that Bgh inoculation results in decreased endogenous ABA levels in an ATAF1-dependent manner, and that the ABA biosynthetic mutant aao3 showed increased penetration resistance to Bgh compared to wild-type plants. Furthermore, we show that ataf1 plants show ABA-hyposensitive phenotypes during seedling development and germination. Our data support a negative correlation between ABA levels and penetration resistance, and identify ATAF1 as a new stimuli-dependent attenuator of ABA signalling for the mediation of efficient penetration resistance in Arabidopsis upon Bgh attack.

198 citations


Cited by
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Journal ArticleDOI
TL;DR: Meta-analysis is used to synthesize data on the response of soil respiration, net N mineralization, and aboveground plant productivity to experimental ecosystem warming at 32 research sites representing four broadly defined biomes, including high (latitude or altitude) tundra, low tundara, grassland, and forest.
Abstract: Climate change due to greenhouse gas emissions is predicted to raise the mean global temperature by 1.0–3.5°C in the next 50–100 years. The direct and indirect effects of this potential increase in temperature on terrestrial ecosystems and ecosystem processes are likely to be complex and highly varied in time and space. The Global Change and Terrestrial Ecosystems core project of the International Geosphere-Biosphere Programme has recently launched a Network of Ecosystem Warming Studies, the goals of which are to integrate and foster research on ecosystem-level effects of rising temperature. In this paper, we use meta-analysis to synthesize data on the response of soil respiration, net N mineralization, and aboveground plant productivity to experimental ecosystem warming at 32 research sites representing four broadly defined biomes, including high (latitude or altitude) tundra, low tundra, grassland, and forest. Warming methods included electrical heat-resistance ground cables, greenhouses, vented and unvented field chambers, overhead infrared lamps, and passive night-time warming. Although results from individual sites showed considerable variation in response to warming, results from the meta-analysis showed that, across all sites and years, 2–9 years of experimental warming in the range 0.3–6.0°C significantly increased soil respiration rates by 20% (with a 95% confidence interval of 18–22%), net N mineralization rates by 46% (with a 95% confidence interval of 30–64%), and plant productivity by 19% (with a 95% confidence interval of 15–23%). The response of soil respiration to warming was generally larger in forested ecosystems compared to low tundra and grassland ecosystems, and the response of plant productivity was generally larger in low tundra ecosystems than in forest and grassland ecosystems. With the exception of aboveground plant productivity, which showed a greater positive response to warming in colder ecosystems, the magnitude of the response of these three processes to experimental warming was not generally significantly related to the geographic, climatic, or environmental variables evaluated in this analysis. This underscores the need to understand the relative importance of specific factors (such as temperature, moisture, site quality, vegetation type, successional status, land-use history, etc.) at different spatial and temporal scales, and suggests that we should be cautious in "scaling up" responses from the plot and site level to the landscape and biome level. Overall, ecosystem-warming experiments are shown to provide valuable insights on the response of terrestrial ecosystems to elevated temperature.

1,988 citations

Journal ArticleDOI
TL;DR: While the intrinsic complexity of natural product-based drug discovery necessitates highly integrated interdisciplinary approaches, the reviewed scientific developments, recent technological advances, and research trends clearly indicate that natural products will be among the most important sources of new drugs in the future.

1,760 citations

Proceedings ArticleDOI
01 Dec 2012
TL;DR: An introduction to event- and self-triggered control systems where sensing and actuation is performed when needed and how these control strategies can be implemented using existing wireless communication technology is shown.
Abstract: Recent developments in computer and communication technologies have led to a new type of large-scale resource-constrained wireless embedded control systems. It is desirable in these systems to limit the sensor and control computation and/or communication to instances when the system needs attention. However, classical sampled-data control is based on performing sensing and actuation periodically rather than when the system needs attention. This paper provides an introduction to event- and self-triggered control systems where sensing and actuation is performed when needed. Event-triggered control is reactive and generates sensor sampling and control actuation when, for instance, the plant state deviates more than a certain threshold from a desired value. Self-triggered control, on the other hand, is proactive and computes the next sampling or actuation instance ahead of time. The basics of these control strategies are introduced together with a discussion on the differences between state feedback and output feedback for event-triggered control. It is also shown how event- and self-triggered control can be implemented using existing wireless communication technology. Some applications to wireless control in process industry are discussed as well.

1,642 citations

Journal ArticleDOI
TL;DR: This review aims to characterize the interaction between biotic and abiotic stress responses at a molecular level, focusing on regulatory mechanisms important to both pathways.
Abstract: Plant responses to different stresses are highly complex and involve changes at the transcriptome, cellular, and physiological levels. Recent evidence shows that plants respond to multiple stresses differently from how they do to individual stresses, activating a specific programme of gene expression relating to the exact environmental conditions encountered. Rather than being additive, the presence of an abiotic stress can have the effect of reducing or enhancing susceptibility to a biotic pest or pathogen, and vice versa. This interaction between biotic and abiotic stresses is orchestrated by hormone signalling pathways that may induce or antagonize one another, in particular that of abscisic acid. Specificity in multiple stress responses is further controlled by a range of molecular mechanisms that act together in a complex regulatory network. Transcription factors, kinase cascades, and reactive oxygen species are key components of this cross-talk, as are heat shock factors and small RNAs. This review aims to characterize the interaction between biotic and abiotic stress responses at a molecular level, focusing on regulatory mechanisms important to both pathways. Identifying master regulators that connect both biotic and abiotic stress response pathways is fundamental in providing opportunities for developing broad-spectrum stress-tolerant crop plants.

1,471 citations

Journal ArticleDOI
01 Apr 1995-Ecology
TL;DR: In this article, the authors manipulated light, temperature, and nutrients in moist tussock tundra near Toolik Lake, Alaska to determine how global changes in these parameters might affect community and ecosystem processes.
Abstract: We manipulated light, temperature, and nutrients in moist tussock tundra near Toolik Lake, Alaska to determine how global changes in these parameters might affect community and ecosystem processes. Some of these manipulations altered nutrient availability, growth—form composition, net primary production, and species richness in less than a decade, indicating that arctic vegetation at this site is sensitive to climatic change. In general, short—term (3—yr) responses were poor predictors of longer term (9—yr) changes in community composition. The longer term responses showed closer correspondence to patterns of vegetation distribution along environmental gradients. Nitrogen and phosphorus availability tended to increase in response to elevated temperature, reflecting increased mineralization, and in response to light attenuation, reflecting reduced nutrient uptake by vegetation. Nutrient addition increased biomass and production of deciduous shrubs but reduced growth of evergreen shrubs and nonvascular plants. Light attenuation reduced biomass of all growth forms. Elevated temperature enhanced shrub production but reduced production of nonvascular plants. These contrasting responses to temperature increase and to nutrient addition by different growth forms "canceled out" at the ecosystem level, buffering changes in ecosystem characteristics such as biomass, production, and nutrient uptake. The major effect of elevated temperature was to speed plant response to changes in soil resources and, in the long term (9 yr), to increase nutrient availability through changes in N mineralization. Species within a growth form were similar to one another in their responses to changes in resources (light or nutrients) but showed no consistent response to evelated temperature. Species richness was reduced 30—50% by temperature and nutrient treatments, due to loss of less abundant species. Declines in diversity occurred disproportionately in forbs, which are important for animal nutrition, and in mosses, which maintain soil thermal regime. There was no increased abundance of initially rare species in response to any treatment. During our 9—yr study (the warmest decade on record in the region), biomass of one dominant tundra species unexpectedly changed in control plots in the direction predicted by our experiments and by Holocene pollen records. This suggests that regional climatic warming may already be altering the species composition of Alaskan arctic tundra.

1,444 citations