@phdthesis{WijesinghaAhchige2022,
  author    = {Wijesingha Ahchige, Micha},
  title     = {Canalization of plant metabolism and yield},
  doi       = {10.25932/publishup-54884},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-548844},
  school      = {Universit{\"a}t Potsdam},
  pages     = {VIII, 160},
  year      = {2022},
  abstract  = {Plant metabolism is the main process of converting assimilated carbon to different crucial compounds for plant growth and therefore crop yield, which makes it an important research topic. Although major advances in understanding genetic principles contributing to metabolism and yield have been made, little is known about the genetics responsible for trait variation or canalization although the concepts have been known for a long time. In light of a growing global population and progressing climate change, understanding canalization of metabolism and yield seems ever-more important to ensure food security. Our group has recently found canalization metabolite quantitative trait loci (cmQTL) for tomato fruit metabolism, showing that the concept of canalization applies on metabolism. In this work two approaches to investigate plant metabolic canalization and one approach to investigate yield canalization are presented. In the first project, primary and secondary metabolic data from Arabidopsis thaliana and Phaseolus vulgaris leaf material, obtained from plants grown under different conditions was used to calculate cross-environment coefficient of variations or fold-changes of metabolite levels per genotype and used as input for genome wide association studies. While primary metabolites have lower CV across conditions and show few and mostly weak associations to genomic regions, secondary metabolites have higher CV and show more, strong metabolite to genome associations. As candidate genes, both potential regulatory genes as well as metabolic genes, can be found, albeit most metabolic genes are rarely directly related to the target metabolites, suggesting a role for both potential regulatory mechanisms as well as metabolic network structure for canalization of metabolism. In the second project, candidate genes of the Solanum lycopersicum cmQTL mapping are selected and CRISPR/Cas9-mediated gene-edited tomato lines are created, to validate the genes role in canalization of metabolism. Obtained mutants appeared to either have strong aberrant developmental phenotypes or appear wild type-like. One phenotypically inconspicuous mutant of a pantothenate kinase, selected as candidate for malic acid canalization shows a significant increase of CV across different watering conditions. Another such mutant of a protein putatively involved in amino acid transport, selected as candidate for phenylalanine canalization shows a similar tendency to increased CV without statistical significance. This potential role of two genes involved in metabolism supports the hypothesis of structural relevance of metabolism for its own stability. In the third project, a mutant for a putative disulfide isomerase, important for thylakoid biogenesis, is characterized by a multi-omics approach. The mutant was characterized previously in a yield stability screening and showed a variegated leaf phenotype, ranging from green leaves with wild type levels of chlorophyll over differently patterned variegated to completely white leaves almost completely devoid of photosynthetic pigments. White mutant leaves show wild type transcript levels of photosystem assembly factors, with the exception of ELIP and DEG orthologs indicating a stagnation at an etioplast to chloroplast transition state. Green mutant leaves show an upregulation of these assembly factors, possibly acting as overcompensation for partially defective disulfide isomerase, which seems sufficient for proper chloroplast development as confirmed by a wild type-like proteome. Likely as a result of this phenotype, a general stress response, a shift to a sink-like tissue and abnormal thylakoid membranes, strongly alter the metabolic profile of white mutant leaves. As the severity and pattern of variegation varies from plant to plant and may be effected by external factors, the effect on yield instability, may be a cause of a decanalized ability to fully exploit the whole leaf surface area for photosynthetic activity.},
  language  = {en}
}
@misc{WagnerHillebrandWackeretal.2013,
  author    = {Wagner, Nicole D. and Hillebrand, Helmut and Wacker, Alexander and Frost, Paul C.},
  title     = {Nutritional indicators and their uses in ecology},
  series = {Ecology letters},
  volume    = {16},
  journal   = {Ecology letters},
  number    = {4},
  publisher = {Wiley-Blackwell},
  address   = {Hoboken},
  issn      = {1461-023X},
  doi       = {10.1111/ele.12067},
  pages     = {535 -- 544},
  year      = {2013},
  abstract  = {The nutrition of animal consumers is an important regulator of ecological processes due to its effects on their physiology, life-history and behaviour. Understanding the ecological effects of poor nutrition depends on correctly diagnosing the nature and strength of nutritional limitation. Despite the need to assess nutritional limitation, current approaches to delineating nutritional constraints can be non-specific and imprecise. Here, we consider the need and potential to develop new complementary approaches to the study of nutritional constraints on animal consumers by studying and using a suite of established and emerging biochemical and molecular responses. These nutritional indicators include gene expression, transcript regulators, protein profiling and activity, and gross biochemical and elemental composition. The potential applications of nutritional indicators to ecological studies are highlighted to demonstrate the value that this approach would have to future studies in community and ecosystem ecology.},
  language  = {en}
}
@phdthesis{Thierbach2004,
  author    = {Thierbach, Ren{\´e}},
  title     = {Identifikation des mitochondrialen Proteins Frataxin als stoffwechselmodulierenden Tumorsuppressor},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-0001943},
  school      = {Universit{\"a}t Potsdam},
  year      = {2004},
  abstract  = {Die Krebsentstehung wurde vor rund 80 Jahren auf ver{\"a}nderten zellul{\"a}ren Energiestoffwechsel zur{\"u}ckgef{\"u}hrt. Diese Hypothese konnte bisher weder experimentell bewiesen noch widerlegt werden. Durch den Einsatz zweier Modellsysteme mit unterschiedlicher Expression des mitochondrialen Proteins Frataxin konnte in der vorliegenden Arbeit gezeigt werden, dass der mitochondriale Energiestoffwechsel einen Einfluss auf die Tumorentstehung zu besitzen scheint. Eine Reduktion des mitochondrialen Energiestoffwechsels wurde durch die hepatozytenspezifische Ausschaltung des mitochondrialen Proteins Frataxin in M{\"a}usen erreicht. Der durch das Cre-/loxP-Rekombinasesystem erreichte organspezifische Knock-out wurde auf Transkriptions- und Translationsebene nachgewiesen. Anhand verminderter Aconitaseaktivit{\"a}t, geringeren Sauerstoffverbrauches und reduzierten ATP-Gehaltes im Lebergewebe wurde ein signifikant verminderter Energiestoffwechsel dargestellt. Zwar entsprach die Genotypenverteilung in den Versuchsgruppen der erwarteten Mendelschen Verteilung, dennoch war die mittlere Lebenserwartung der Knock-out-Tiere mit ca. 30 Wochen stark reduziert. Bereits in jungem Alter war bei diesen Tieren die Ausbildung von pr{\"a}neoplastischen Herden zu beobachten. Mit proteinbiochemischen Nachweistechniken konnte in Lebergewebe 4-8 Wochen alter Tiere eine verst{\"a}rkte Aktivierung des Apoptosesignalweges (Cytochrom C im Zytosol, verst{\"a}rkte Expression von Bax) sowie eine Modulation stressassoziierter Proteine (geringere Phosphorylierungsrate p38-MAPK, vermehrte Expression HSP-25, verminderte Expression HSP-70) aufgezeigt werden. Im inversen Ansatz wurde eine Steigerung des mitochondrialen Energiestoffwechsels durch stabile transgene Frataxin{\"u}berexpression in zwei Kolonkarzinomzelllinien erreicht. Diese Steigerung zeigte sich durch erh{\"o}hte Aconitaseaktivit{\"a}t, erh{\"o}hten Sauerstoffverbrauch, gesteigertes mitochondriales Membranpotenzial und erh{\"o}hten ATP-Gehalt in den Zellen. Die frataxin{\"u}berexprimierenden Zellen wuchsen signifikant langsamer als Kontrollzellen und zeigten im Soft-Agar-Assay und im Nacktmausmodell ein deutlich geringeres Potenzial zur Ausbildung von Kolonien bzw. Tumoren. Mittels Immunoblot war hier eine vermehrte Phosphorylierung der p38-MAPK festzustellen. Die zusammenfassende Betrachtung beider Modelle zeigt, dass ein reduzierter mitochondrialer Energiestoffwechsel durch Regulation der p38-MAPK und apoptotischer Signalwege ein erh{\"o}htes Krebsrisiko zu verursachen vermag.},
  language  = {de}
}
@article{SchwahnBeleggiaOmranianetal.2017,
  author    = {Schwahn, Kevin and Beleggia, Romina and Omranian, Nooshin and Nikoloski, Zoran},
  title     = {Stoichiometric Correlation Analysis: Principles of Metabolic Functionality from Metabolomics Data},
  series = {Frontiers in plant science},
  volume    = {8},
  journal   = {Frontiers in plant science},
  publisher = {Frontiers Research Foundation},
  address   = {Lausanne},
  issn      = {1664-462X},
  doi       = {10.3389/fpls.2017.02152},
  pages     = {12},
  year      = {2017},
  abstract  = {Recent advances in metabolomics technologies have resulted in high-quality (time-resolved) metabolic profiles with an increasing coverage of metabolic pathways. These data profiles represent read-outs from often non-linear dynamics of metabolic networks. Yet, metabolic profiles have largely been explored with regression-based approaches that only capture linear relationships, rendering it difficult to determine the extent to which the data reflect the underlying reaction rates and their couplings. Here we propose an approach termed Stoichiometric Correlation Analysis (SCA) based on correlation between positive linear combinations of log-transformed metabolic profiles. The log-transformation is due to the evidence that metabolic networks can be modeled by mass action law and kinetics derived from it. Unlike the existing approaches which establish a relation between pairs of metabolites, SCA facilitates the discovery of higherorder dependence between more than two metabolites. By using a paradigmatic model of the tricarboxylic acid cycle we show that the higher-order dependence reflects the coupling of concentration of reactant complexes, capturing the subtle difference between the employed enzyme kinetics. Using time-resolved metabolic profiles from Arabidopsis thaliana and Escherichia coli, we show that SCA can be used to quantify the difference in coupling of reactant complexes, and hence, reaction rates, underlying the stringent response in these model organisms. By using SCA with data from natural variation of wild and domesticated wheat and tomato accession, we demonstrate that the domestication is accompanied by loss of such couplings, in these species. Therefore, application of SCA to metabolomics data from natural variation in wild and domesticated populations provides a mechanistic way to understanding domestication and its relation to metabolic networks.},
  language  = {en}
}
@phdthesis{Schlossarek2023,
  author    = {Schlossarek, Dennis},
  title     = {Identification of dynamic protein-metabolite complexes in saccharomyces cerevisiae using co-fractionation mass spectrometry},
  doi       = {10.25932/publishup-58282},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-582826},
  school      = {Universit{\"a}t Potsdam},
  pages     = {123},
  year      = {2023},
  abstract  = {Cells are built from a variety of macromolecules and metabolites. Both, the proteome and the metabolome are highly dynamic and responsive to environmental cues and developmental processes. But it is not their bare numbers, but their interactions that enable life. The protein-protein (PPI) and protein-metabolite interactions (PMI) facilitate and regulate all aspects of cell biology, from metabolism to mitosis. Therefore, the study of PPIs and PMIs and their dynamics in a cell-wide context is of great scientific interest. In this dissertation, I aim to chart a map of the dynamic PPIs and PMIs across metabolic and cellular transitions. As a model system, I study the shift from the fermentative to the respiratory growth, known as the diauxic shift, in the budding yeast Saccharomyces cerevisiae. To do so, I am applying a co-fractionation mass spectrometry (CF-MS) based method, dubbed protein metabolite interactions using size separation (PROMIS). PROMIS, as well as comparable methods, will be discussed in detail in chapter 1. Since PROMIS was developed originally for Arabidopsis thaliana, in chapter 2, I will describe the adaptation of PROMIS to S. cerevisiae. Here, the obtained results demonstrated a wealth of protein-metabolite interactions, and experimentally validated 225 previously predicted PMIs. Applying orthogonal, targeted approaches to validate the interactions of a proteogenic dipeptide, Ser-Leu, five novel protein-interactors were found. One of those proteins, phosphoglycerate kinase, is inhibited by Ser-Leu, placing the dipeptide at the regulation of glycolysis. In chapter 3, I am presenting PROMISed, a novel web-tool designed for the analysis of PROMIS- and other CF-MS-datasets. Starting with raw fractionation profiles, PROMISed enables data pre-processing, profile deconvolution, scores differences in fractionation profiles between experimental conditions, and ultimately charts interaction networks. PROMISed comes with a user-friendly graphic interface, and thus enables the routine analysis of CF-MS data by non-computational biologists. Finally, in chapter 4, I applied PROMIS in combination with the isothermal shift assay to the diauxic shift in S. cerevisiae to study changes in the PPI and PMI landscape across this metabolic transition. I found a major rewiring of protein-protein-metabolite complexes, exemplified by the disassembly of the proteasome in the respiratory phase, the loss of interaction of an enzyme involved in amino acid biosynthesis and its cofactor, as well as phase and structure specific interactions between dipeptides and enzymes of central carbon metabolism. In chapter 5, I am summarizing the presented results, and discuss a strategy to unravel the potential patterns of dipeptide accumulation and binding specificities. Lastly, I recapitulate recently postulated guidelines for CF-MS experiments, and give an outlook of protein interaction studies in the near future.},
  language  = {en}
}
@article{SchellWardelmannKleinridders2021,
  author    = {Schell, Mareike and Wardelmann, Kristina and Kleinridders, Andre},
  title     = {Untangling the effect of insulin action on brain mitochondria and metabolism},
  series = {Journal of neuroendocrinology},
  volume    = {33},
  journal   = {Journal of neuroendocrinology},
  number    = {4},
  publisher = {Wiley},
  address   = {Hoboken},
  issn      = {0953-8194},
  doi       = {10.1111/jne.12932},
  pages     = {14},
  year      = {2021},
  abstract  = {The regulation of energy homeostasis is controlled by the brain and, besides requiring high amounts of energy, it relies on functional insulin/insulin-like growth factor (IGF)-1 signalling in the central nervous system. This energy is mainly provided by mitochondria in form of ATP. Thus, there is an intricate interplay between mitochondrial function and insulin/IGF-1 action to enable functional brain signalling and, accordingly, propagate a healthy metabolism. To adapt to different nutritional conditions, the brain is able to sense the current energy status via mitochondrial and insulin signalling-dependent pathways and exerts an appropriate metabolic response. However, regional, cell type and receptor-specific consequences of this interaction occur and are linked to diverse outcomes such as altered nutrient sensing, body weight regulation or even cognitive function. Impairments of this cross-talk can lead to obesity and glucose intolerance and are linked to neurodegenerative diseases, yet they also induce a self-sustainable, dysfunctional 'metabolic triangle' characterised by insulin resistance, mitochondrial dysfunction and inflammation in the brain. The identification of causal factors deteriorating insulin action, mitochondrial function and concomitantly a signature of metabolic stress in the brain is of utter importance to offer novel mechanistic insights into development of the continuously rising prevalence of non-communicable diseases such as type 2 diabetes and neurodegeneration. This review aims to determine the effect of insulin action on brain mitochondrial function and energy metabolism. It precisely outlines the interaction and differences between insulin action, insulin-like growth factor (IGF)-1 signalling and mitochondrial function; distinguishes between causality and association; and reveals its consequences for metabolism and cognition. We hypothesise that an improvement of at least one signalling pathway can overcome the vicious cycle of a self-perpetuating metabolic dysfunction in the brain present in metabolic and neurodegenerative diseases.},
  language  = {en}
}
@article{ScharnweberAnderssonChaguacedaetal.2021,
  author    = {Scharnweber, Inga Kristin and Andersson, Matilda L. and Chaguaceda, Fernando and Ekl{\"o}v, Peter},
  title     = {Intraspecific differences in metabolic rates shape carbon stable isotope trophic discrimination factors of muscle tissue in the common teleost Eurasian perch (Perca fluviatilis)},
  series = {Ecology and evolution},
  volume    = {11},
  journal   = {Ecology and evolution},
  number    = {14},
  publisher = {John Wiley \& Sons, Inc.},
  address   = {New Jersey},
  issn      = {2045-7758},
  pages     = {9804 -- 9814},
  year      = {2021},
  abstract  = {Stable isotopes represent a unique approach to provide insights into the ecology of organisms. δ13C and δ15N have specifically been used to obtain information on the trophic ecology and food-web interactions. Trophic discrimination factors (TDF, Δ13C and Δ15N) describe the isotopic fractionation occurring from diet to consumer tissue, and these factors are critical for obtaining precise estimates within any application of δ13C and δ15N values. It is widely acknowledged that metabolism influences TDF, being responsible for different TDF between tissues of variable metabolic activity (e.g., liver vs. muscle tissue) or species body size (small vs. large). However, the connection between the variation of metabolism occurring within a single species during its ontogeny and TDF has rarely been considered. Here, we conducted a 9-month feeding experiment to report Δ13C and Δ15N of muscle and liver tissues for several weight classes of Eurasian perch (Perca fluviatilis), a widespread teleost often studied using stable isotopes, but without established TDF for feeding on a natural diet. In addition, we assessed the relationship between the standard metabolic rate (SMR) and TDF by measuring the oxygen consumption of the individuals. Our results showed a significant negative relationship of SMR with Δ13C, and a significant positive relationship of SMR with Δ15N of muscle tissue, but not with TDF of liver tissue. SMR varies inversely with size, which translated into a significantly different TDF of muscle tissue between size classes. In summary, our results emphasize the role of metabolism in shaping-specific TDF (i.e., Δ13C and Δ15N of muscle tissue) and especially highlight the substantial differences between individuals of different ontogenetic stages within a species. Our findings thus have direct implications for the use of stable isotope data and the applications of stable isotopes in food-web studies.},
  language  = {en}
}
@misc{ScharnweberAnderssonChaguacedaetal.2021,
  author    = {Scharnweber, Inga Kristin and Andersson, Matilda L. and Chaguaceda, Fernando and Ekl{\"o}v, Peter},
  title     = {Intra-specific differences in metabolic rates shape carbon stable isotope trophic discrimination factors of muscle tissue in the common teleost Eurasian perch (Perca fluviatilis)},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {14},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-52401},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-524015},
  pages     = {13},
  year      = {2021},
  abstract  = {Stable isotopes represent a unique approach to provide insights into the ecology of organisms. δ13C and δ15N have specifically been used to obtain information on the trophic ecology and food-web interactions. Trophic discrimination factors (TDF, Δ13C and Δ15N) describe the isotopic fractionation occurring from diet to consumer tissue, and these factors are critical for obtaining precise estimates within any application of δ13C and δ15N values. It is widely acknowledged that metabolism influences TDF, being responsible for different TDF between tissues of variable metabolic activity (e.g., liver vs. muscle tissue) or species body size (small vs. large). However, the connection between the variation of metabolism occurring within a single species during its ontogeny and TDF has rarely been considered. Here, we conducted a 9-month feeding experiment to report Δ13C and Δ15N of muscle and liver tissues for several weight classes of Eurasian perch (Perca fluviatilis), a widespread teleost often studied using stable isotopes, but without established TDF for feeding on a natural diet. In addition, we assessed the relationship between the standard metabolic rate (SMR) and TDF by measuring the oxygen consumption of the individuals. Our results showed a significant negative relationship of SMR with Δ13C, and a significant positive relationship of SMR with Δ15N of muscle tissue, but not with TDF of liver tissue. SMR varies inversely with size, which translated into a significantly different TDF of muscle tissue between size classes. In summary, our results emphasize the role of metabolism in shaping-specific TDF (i.e., Δ13C and Δ15N of muscle tissue) and especially highlight the substantial differences between individuals of different ontogenetic stages within a species. Our findings thus have direct implications for the use of stable isotope data and the applications of stable isotopes in food-web studies.},
  language  = {en}
}
@phdthesis{RodriguezCubillos2018,
  author    = {Rodriguez Cubillos, Andres Eduardo},
  title     = {Understanding the impact of heterozygosity on metabolism, growth and hybrid necrosis within a local Arabidopsis thaliana collection site},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-416758},
  school      = {Universit{\"a}t Potsdam},
  pages     = {106},
  year      = {2018},
  abstract  = {Plants are unable to move away from unwanted environments and therefore have to locally adapt to changing conditions. Arabidopsis thaliana (Arabidopsis), a model organism in plant biology, has been able to rapidly colonize a wide spectrum of environments with different biotic and abiotic challenges. In recent years, natural variation in Arabidopsis has shown to be an excellent resource to study genes underlying adaptive traits and hybridization's impact on natural diversity. Studies on Arabidopsis hybrids have provided information on the genetic basis of hybrid incompatibilities and heterosis, as well as inheritance patterns in hybrids. However, previous studies have focused mainly on global accessions and yet much remains to be known about variation happening within a local growth habitat. In my PhD, I investigated the impact of heterozygosity at a local collection site of Arabidopsis and its role in local adaptation. I focused on two different projects, both including hybrids among Arabidopsis individuals collected around T{\"u}bingen in Southern Germany. The first project sought to understand the impact of hybridization on metabolism and growth within a local Arabidopsis collection site. For this, the inheritance patterns in primary and secondary metabolism, together with rosette size of full diallel crosses among seven parents originating from Southern Germany were analyzed. In comparison to primary metabolites, compounds from secondary metabolism were more variable and showed pronounced non-additive inheritance patterns. In addition, defense metabolites, mainly glucosinolates, displayed the highest degree of variation from the midparent values and were positively correlated with a proxy for plant size. In the second project, the role of ACCELERATED CELL DEATH 6 (ACD6) in the defense response pathway of Arabidopsis necrotic hybrids was further characterized. Allelic interactions of ACD6 have been previously linked to hybrid necrosis, both among global and local Arabidopsis accessions. Hence, I characterized the early metabolic and ionic changes induced by ACD6, together with marker gene expression assays of physiological responses linked to its activation. An upregulation of simple sugars and metabolites linked to non-enzymatic antioxidants and the TCA cycle were detected, together with putrescine and acids linked to abiotic stress responses. Senescence was found to be induced earlier in necrotic hybrids and cytoplasmic calcium signaling was unaffected in response to temperature. In parallel, GFP-tagged constructs of ACD6 were developed. This work therefore gave novel insights on the role of heterozygosity in natural variation and adaptation and expanded our current knowledge on the physiological and molecular responses associated with ACD6 activation.},
  language  = {en}
}
@phdthesis{Mubeen2018,
  author    = {Mubeen, Umarah},
  title     = {Regulation of central carbon and nitrogen metabolism by Target of Rapamycin (TOR) kinase in Chlamydomonas reinhardtii},
  school      = {Universit{\"a}t Potsdam},
  pages     = {vii, 153},
  year      = {2018},
  abstract  = {The highly conserved protein complex containing the Target of Rapamycin (TOR) kinase is known to integrate intra- and extra-cellular stimuli controlling nutrient allocation and cellular growth. This thesis describes three studies aimed to understand how TOR signaling pathway influences carbon and nitrogen metabolism in Chlamydomonas reinhardtii. The first study presents a time-resolved analysis of the molecular and physiological features across the diurnal cycle. The inhibition of TOR leads to 50\% reduction in growth followed by nonlinear delays in the cell cycle progression. The metabolomics analysis showed that the growth repression is mainly driven by differential carbon partitioning between anabolic and catabolic processes. Furthermore, the high accumulation of nitrogen-containing compounds indicated that TOR kinase controls the carbon to nitrogen balance of the cell, which is responsible for biomass accumulation, growth and cell cycle progression. In the second study the cause of the high accumulation of amino acids is explained. For this purpose, the effect of TOR inhibition on Chlamydomonas was examined under different growth regimes using stable 13C- and 15N-isotope labeling. The data clearly showed that an increased nitrogen uptake is induced within minutes after the inhibition of TOR. Interestingly, this increased N-influx is accompanied by increased activities of nitrogen assimilating enzymes. Accordingly, it was concluded that TOR inhibition induces de-novo amino acid synthesis in Chlamydomonas. The recognition of this novel process opened an array of questions regarding potential links between central metabolism and TOR signaling. Therefore a detailed phosphoproteomics study was conducted to identify the potential substrates of TOR pathway regulating central metabolism. Interestingly, some of the key enzymes involved in carbon metabolism as well as amino acid synthesis exhibited significant changes in the phosphosite intensities immediately after TOR inhibition. Altogether, these studies provide a) detailed insights to metabolic response of Chlamydomonas to TOR inhibition, b) identification of a novel process causing rapid upshifts in amino acid levels upon TOR inhibition and c) finally highlight potential targets of TOR signaling regulating changes in central metabolism. Further biochemical and molecular investigations could confirm these observations and advance the understanding of growth signaling in microalgae.},
  language  = {en}
}