@article{TenenboimSmirnovaWillmitzeretal.2014, author = {Tenenboim, Hezi and Smirnova, Julia and Willmitzer, Lothar and Steup, Martin and Brotman, Yariv}, title = {VMP1-deficient Chlamydomonas exhibits severely aberrant cell morphology and disrupted cytokinesies}, series = {BMC plant biology}, volume = {14}, journal = {BMC plant biology}, publisher = {BioMed Central}, address = {London}, issn = {1471-2229}, doi = {10.1186/1471-2229-14-121}, pages = {13}, year = {2014}, abstract = {Background: The versatile Vacuole Membrane Protein 1 (VMP1) has been previously investigated in six species. It has been shown to be essential in macroautophagy, where it takes part in autophagy initiation. In addition, VMP1 has been implicated in organellar biogenesis; endo-, exo- and phagocytosis, and protein secretion; apoptosis; and cell adhesion. These roles underly its proven involvement in pancreatitis, diabetes and cancer in humans. Results: In this study we analyzed a VMP1 homologue from the green alga Chlamydomonas reinhardtii. CrVMP1 knockdown lines showed severe phenotypes, mainly affecting cell division as well as the morphology of cells and organelles. We also provide several pieces of evidence for its involvement in macroautophagy.}, language = {en} } @article{deAbreueLimaLiWenetal.2018, author = {de Abreu e Lima, Francisco Anastacio and Li, Kun and Wen, Weiwei and Yan, Jianbing and Nikoloski, Zoran and Willmitzer, Lothar and Brotman, Yariv}, title = {Unraveling lipid metabolism in maize with time-resolved multi-omics data}, series = {The plant journal}, volume = {93}, journal = {The plant journal}, number = {6}, publisher = {Wiley}, address = {Hoboken}, issn = {0960-7412}, doi = {10.1111/tpj.13833}, pages = {1102 -- 1115}, year = {2018}, abstract = {Maize is the cereal crop with the highest production worldwide, and its oil is a key energy resource. Improving the quantity and quality of maize oil requires a better understanding of lipid metabolism. To predict the function of maize genes involved in lipid biosynthesis, we assembled transcriptomic and lipidomic data sets from leaves of B73 and the high-oil line By804 in two distinct time-series experiments. The integrative analysis based on high-dimensional regularized regression yielded lipid-transcript associations indirectly validated by Gene Ontology and promoter motif enrichment analyses. The co-localization of lipid-transcript associations using the genetic mapping of lipid traits in leaves and seedlings of a B73 x By804 recombinant inbred line population uncovered 323 genes involved in the metabolism of phospholipids, galactolipids, sulfolipids and glycerolipids. The resulting association network further supported the involvement of 50 gene candidates in modulating levels of representatives from multiple acyl-lipid classes. Therefore, the proposed approach provides high-confidence candidates for experimental testing in maize and model plant species.}, language = {en} } @article{BrotmanLandauPninietal.2012, author = {Brotman, Yariv and Landau, Udi and Pnini, Smadar and Lisec, Jan and Balazadeh, Salma and M{\"u}ller-R{\"o}ber, Bernd and Zilberstein, Aviah and Willmitzer, Lothar and Chet, Ilan and Viterbo, Ada}, title = {The LysM Receptor-Like Kinase LysM RLK1 is required to activate defense and abiotic-stress responses induced by overexpression of fungal chitinases in arabidopsis plants}, series = {Molecular plant}, volume = {5}, journal = {Molecular plant}, number = {5}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {1674-2052}, doi = {10.1093/mp/sss021}, pages = {1113 -- 1124}, year = {2012}, abstract = {Application of crab shell chitin or pentamer chitin oligosaccharide to Arabidopsis seedlings increased tolerance to salinity in wild-type but not in knockout mutants of the LysM Receptor-Like Kinase1 (CERK1/LysM RLK1) gene, known to play a critical role in signaling defense responses induced by exogenous chitin. Arabidopsis plants overexpressing the endochitinase chit36 and hexoaminidase excy1 genes from the fungus Trichoderma asperelleoides T203 showed increased tolerance to salinity, heavy-metal stresses, and Botrytis cinerea infection. Resistant lines, overexpressing fungal chitinases at different levels, were outcrossed to lysm rlk1 mutants. Independent homozygous hybrids lost resistance to biotic and abiotic stresses, despite enhanced chitinase activity. Expression analysis of 270 stress-related genes, including those induced by reactive oxygen species (ROS) and chitin, revealed constant up-regulation (at least twofold) of 10 genes in the chitinase-overexpressing line and an additional 76 salt-induced genes whose expression was not elevated in the lysm rlk1 knockout mutant or the hybrids harboring the mutation. These findings elucidate that chitin-induced signaling mediated by LysM RLK1 receptor is not limited to biotic stress response but also encompasses abiotic-stress signaling and can be conveyed by ectopic expression of chitinases in plants.}, language = {en} } @article{MettlerMuehlhausHemmeetal.2014, author = {Mettler, Tabea and M{\"u}hlhaus, Timo and Hemme, Dorothea and Sch{\"o}ttler, Mark Aurel and Rupprecht, Jens and Idoine, Adam and Veyel, Daniel and Pal, Sunil Kumar and Yaneva-Roder, Liliya and Winck, Flavia Vischi and Sommer, Frederik and Vosloh, Daniel and Seiwert, Bettina and Erban, Alexander and Burgos, Asdrubal and Arvidsson, Samuel Janne and Schoenfelder, Stephanie and Arnold, Anne and Guenther, Manuela and Krause, Ursula and Lohse, Marc and Kopka, Joachim and Nikoloski, Zoran and M{\"u}ller-R{\"o}ber, Bernd and Willmitzer, Lothar and Bock, Ralph and Schroda, Michael and Stitt, Mark}, title = {Systems analysis of the response of photosynthesis, metabolism, and growth to an increase in irradiance in the photosynthetic model organism chlamydomonas reinhardtii}, series = {The plant cell}, volume = {26}, journal = {The plant cell}, number = {6}, publisher = {American Society of Plant Physiologists}, address = {Rockville}, issn = {1040-4651}, doi = {10.1105/tpc.114.124537}, pages = {2310 -- 2350}, year = {2014}, abstract = {We investigated the systems response of metabolism and growth after an increase in irradiance in the nonsaturating range in the algal model Chlamydomonas reinhardtii. In a three-step process, photosynthesis and the levels of metabolites increased immediately, growth increased after 10 to 15 min, and transcript and protein abundance responded by 40 and 120 to 240 min, respectively. In the first phase, starch and metabolites provided a transient buffer for carbon until growth increased. This uncouples photosynthesis from growth in a fluctuating light environment. In the first and second phases, rising metabolite levels and increased polysome loading drove an increase in fluxes. Most Calvin-Benson cycle (CBC) enzymes were substrate-limited in vivo, and strikingly, many were present at higher concentrations than their substrates, explaining how rising metabolite levels stimulate CBC flux. Rubisco, fructose-1,6-biosphosphatase, and seduheptulose-1,7-bisphosphatase were close to substrate saturation in vivo, and flux was increased by posttranslational activation. In the third phase, changes in abundance of particular proteins, including increases in plastidial ATP synthase and some CBC enzymes, relieved potential bottlenecks and readjusted protein allocation between different processes. Despite reasonable overall agreement between changes in transcript and protein abundance (R-2 = 0.24), many proteins, including those in photosynthesis, changed independently of transcript abundance.}, language = {en} } @misc{SzymanskiJozefczukNikoloskietal.2009, author = {Szymanski, Jedrzej and Jozefczuk, Szymon and Nikoloski, Zoran and Selbig, Joachim and Nikiforova, Victoria and Catchpole, Gareth and Willmitzer, Lothar}, title = {Stability of metabolic correlations under changing environmental conditions in Escherichia coli : a systems approach}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-45253}, year = {2009}, abstract = {Background: Biological systems adapt to changing environments by reorganizing their cellula r and physiological program with metabolites representing one important response level. Different stresses lead to both conserved and specific responses on the metabolite level which should be reflected in the underl ying metabolic network. Methodology/Principal Findings: Starting from experimental data obtained by a GC-MS based high-throughput metabolic profiling technology we here develop an approach that: (1) extracts network representations from metabolic conditiondependent data by using pairwise correlations, (2) determines the sets of stable and condition-dependent correlations based on a combination of statistical significance and homogeneity tests, and (3) can identify metabolites related to the stress response, which goes beyond simple ob servation s about the changes of metabolic concentrations. The approach was tested with Escherichia colias a model organism observed under four different environmental stress conditions (cold stress, heat stress, oxidative stress, lactose diau xie) and control unperturbed conditions. By constructing the stable network component, which displays a scale free topology and small-world characteristics, we demonstrated that: (1) metabolite hubs in this reconstructed correlation networks are significantly enriched for those contained in biochemical networks such as EcoCyc, (2) particular components of the stable network are enriched for functionally related biochemical path ways, and (3) ind ependently of the response scale, based on their importance in the reorganization of the cor relation network a set of metabolites can be identified which represent hypothetical candidates for adjusting to a stress-specific response. Conclusions/Significance: Network-based tools allowed the identification of stress-dependent and general metabolic correlation networks. This correlation-network-ba sed approach does not rely on major changes in concentration to identify metabolites important for st ress adaptation, but rather on the changes in network properties with respect to metabolites. This should represent a useful complementary technique in addition to more classical approaches.}, language = {en} } @article{MeyerKustererLisecetal.2009, author = {Meyer, Rhonda Christiane and Kusterer, Barbara and Lisec, Jan and Steinfath, Matthias and Becher, Martina and Scharr, Hanno and Melchinger, Albrecht E. and Selbig, Joachim and Schurr, Ulrich and Willmitzer, Lothar and Altmann, Thomas}, title = {QTL analysis of early stage heterosis for biomass in Arabidopsis}, series = {Theoretical and applied genetics}, volume = {129}, journal = {Theoretical and applied genetics}, number = {2}, publisher = {Springer Nature}, address = {Berlin}, issn = {1432-2242}, doi = {10.1007/s00122-009-1074-6}, pages = {227 -- 237}, year = {2009}, abstract = {The main objective of this study was to identify genomic regions involved in biomass heterosis using QTL, generation means, and mode-of-inheritance classification analyses. In a modified North Carolina Design III we backcrossed 429 recombinant inbred line and 140 introgression line populations to the two parental accessions, C24 and Col-0, whose F 1 hybrid exhibited 44\% heterosis for biomass. Mid-parent heterosis in the RILs ranged from -31 to 99\% for dry weight and from -58 to 143\% for leaf area. We detected ten genomic positions involved in biomass heterosis at an early developmental stage, individually explaining between 2.4 and 15.7\% of the phenotypic variation. While overdominant gene action was prevalent in heterotic QTL, our results suggest that a combination of dominance, overdominance and epistasis is involved in biomass heterosis in this Arabidopsis cross.}, language = {en} } @misc{MeyerKustererLisecetal.2009, author = {Meyer, Rhonda Christiane and Kusterer, Barbara and Lisec, Jan and Steinfath, Matthias and Becher, Martina and Scharr, Hanno and Melchinger, Albrecht E. and Selbig, Joachim and Schurr, Ulrich and Willmitzer, Lothar and Altmann, Thomas}, title = {QTL analysis of early stage heterosis for biomass in Arabidopsis}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {1330}, issn = {1866-8372}, doi = {10.25932/publishup-43127}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-431272}, pages = {11}, year = {2009}, abstract = {The main objective of this study was to identify genomic regions involved in biomass heterosis using QTL, generation means, and mode-of-inheritance classification analyses. In a modified North Carolina Design III we backcrossed 429 recombinant inbred line and 140 introgression line populations to the two parental accessions, C24 and Col-0, whose F 1 hybrid exhibited 44\% heterosis for biomass. Mid-parent heterosis in the RILs ranged from -31 to 99\% for dry weight and from -58 to 143\% for leaf area. We detected ten genomic positions involved in biomass heterosis at an early developmental stage, individually explaining between 2.4 and 15.7\% of the phenotypic variation. While overdominant gene action was prevalent in heterotic QTL, our results suggest that a combination of dominance, overdominance and epistasis is involved in biomass heterosis in this Arabidopsis cross.}, language = {en} } @misc{SteinfathGaertnerLisecetal.2009, author = {Steinfath, Matthias and G{\"a}rtner, Tanja and Lisec, Jan and Meyer, Rhonda C. and Altmann, Thomas and Willmitzer, Lothar and Selbig, Joachim}, title = {Prediction of hybrid biomass in Arabidopsis thaliana by selected parental SNP and metabolic markers}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {1324}, issn = {1866-8372}, doi = {10.25932/publishup-43111}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-431115}, pages = {9}, year = {2009}, abstract = {A recombinant inbred line (RIL) population, derived from two Arabidopsis thaliana accessions, and the corresponding testcrosses with these two original accessions were used for the development and validation of machine learning models to predict the biomass of hybrids. Genetic and metabolic information of the RILs served as predictors. Feature selection reduced the number of variables (genetic and metabolic markers) in the models by more than 80\% without impairing the predictive power. Thus, potential biomarkers have been revealed. Metabolites were shown to bear information on inherited macroscopic phenotypes. This proof of concept could be interesting for breeders. The example population exhibits substantial mid-parent biomass heterosis. The results of feature selection could therefore be used to shed light on the origin of heterosis. In this respect, mainly dominance effects were detected.}, language = {en} } @article{SteinfathGaertnerLisecetal.2009, author = {Steinfath, Matthias and G{\"a}rtner, Tanja and Lisec, Jan and Meyer, Rhonda Christiane and Altmann, Thomas and Willmitzer, Lothar and Selbig, Joachim}, title = {Prediction of hybrid biomass in Arabidopsis thaliana by selected parental SNP and metabolic markers}, series = {Theoretical and applied genetics : TAG ; international journal of plant breeding research}, volume = {120}, journal = {Theoretical and applied genetics : TAG ; international journal of plant breeding research}, publisher = {Springer}, address = {Berlin}, issn = {0040-5752}, doi = {10.1007/s00122-009-1191-2}, pages = {239 -- 247}, year = {2009}, abstract = {A recombinant inbred line (RIL) population, derived from two Arabidopsis thaliana accessions, and the corresponding testcrosses with these two original accessions were used for the development and validation of machine learning models to predict the biomass of hybrids. Genetic and metabolic information of the RILs served as predictors. Feature selection reduced the number of variables (genetic and metabolic markers) in the models by more than 80\% without impairing the predictive power. Thus, potential biomarkers have been revealed. Metabolites were shown to bear information on inherited macroscopic phenotypes. This proof of concept could be interesting for breeders. The example population exhibits substantial mid-parent biomass heterosis. The results of feature selection could therefore be used to shed light on the origin of heterosis. In this respect, mainly dominance effects were detected.}, language = {en} } @article{CatchpolePlatzerWeikertetal.2011, author = {Catchpole, Gareth and Platzer, Alexander and Weikert, Cornelia and Kempkensteffen, Carsten and Johannsen, Manfred and Krause, Hans and Jung, Klaus and Miller, Kurt and Willmitzer, Lothar and Selbig, Joachim and Weikert, Steffen}, title = {Metabolic profiling reveals key metabolic features of renal cell carcinoma}, series = {Journal of cellular and molecular medicine : a journal of translational medicine}, volume = {15}, journal = {Journal of cellular and molecular medicine : a journal of translational medicine}, number = {1}, publisher = {Wiley-Blackwell}, address = {Malden}, issn = {1582-1838}, doi = {10.1111/j.1582-4934.2009.00939.x}, pages = {109 -- 118}, year = {2011}, abstract = {Recent evidence suggests that metabolic changes play a pivotal role in the biology of cancer and in particular renal cell carcinoma (RCC). Here, a global metabolite profiling approach was applied to characterize the metabolite pool of RCC and normal renal tissue. Advanced decision tree models were applied to characterize the metabolic signature of RCC and to explore features of metastasized tumours. The findings were validated in a second independent dataset. Vitamin E derivates and metabolites of glucose, fatty acid, and inositol phosphate metabolism determined the metabolic profile of RCC. alpha-tocopherol, hippuric acid, myoinositol, fructose-1-phosphate and glucose-1-phosphate contributed most to the tumour/normal discrimination and all showed pronounced concentration changes in RCC. The identified metabolic profile was characterized by a low recognition error of only 5\% for tumour versus normal samples. Data on metastasized tumours suggested a key role for metabolic pathways involving arachidonic acid, free fatty acids, proline, uracil and the tricarboxylic acid cycle. These results illustrate the potential of mass spectroscopy based metabolomics in conjunction with sophisticated data analysis methods to uncover the metabolic phenotype of cancer. Differentially regulated metabolites, such as vitamin E compounds, hippuric acid and myoinositol, provide leads for the characterization of novel pathways in RCC.}, language = {en} }