Education & Certifications


  • PMP, Project Management Institute (2019)
  • PhD, University of Cologne (2012)
  • PostDoc, Stanford University (2019)
  • PostDoc, Plant Systems Biology - VIB - Ghent University (2015)

All Publications


  • Multiomic analysis reveals cell-type-specific molecular determinants of COVID-19 severity. Cell systems Zhang, S., Cooper-Knock, J., Weimer, A. K., Shi, M., Kozhaya, L., Unutmaz, D., Harvey, C., Julian, T. H., Furini, S., Frullanti, E., Fava, F., Renieri, A., Gao, P., Shen, X., Timpanaro, I. S., Kenna, K. P., Baillie, J. K., Davis, M. M., Tsao, P. S., Snyder, M. P. 2022

    Abstract

    The determinants of severe COVID-19 in healthy adults are poorly understood, which limits the opportunity for early intervention. We present a multiomic analysis using machine learning to characterize the genomic basis of COVID-19 severity. We use single-cell multiome profiling of human lungs to link genetic signals to cell-type-specific functions. We discover >1,000 risk genes across 19 cell types, which account for 77% of the SNP-based heritability for severe disease. Genetic risk is particularly focused within natural killer (NK) cells and T cells, placing the dysfunction of these cells upstream of severe disease. Mendelian randomization and single-cell profiling of human NK cells support the role of NK cells and further localize genetic risk to CD56bright NK cells, which are key cytokine producers during the innate immune response. Rare variant analysis confirms the enrichment of severe-disease-associated genetic variation within NK-cell risk genes. Our study provides insights into the pathogenesis of severe COVID-19 with potential therapeutic targets.

    View details for DOI 10.1016/j.cels.2022.05.007

    View details for PubMedID 35690068

  • MITI minimum information guidelines for highly multiplexed tissue images. Nature methods Schapiro, D., Yapp, C., Sokolov, A., Reynolds, S. M., Chen, Y., Sudar, D., Xie, Y., Muhlich, J., Arias-Camison, R., Arena, S., Taylor, A. J., Nikolov, M., Tyler, M., Lin, J., Burlingame, E. A., Human Tumor Atlas Network, Chang, Y. H., Farhi, S. L., Thorsson, V., Venkatamohan, N., Drewes, J. L., Pe'er, D., Gutman, D. A., Herrmann, M. D., Gehlenborg, N., Bankhead, P., Roland, J. T., Herndon, J. M., Snyder, M. P., Angelo, M., Nolan, G., Swedlow, J. R., Schultz, N., Merrick, D. T., Mazzili, S. A., Cerami, E., Rodig, S. J., Santagata, S., Sorger, P. K., Abravanel, D. L., Achilefu, S., Ademuyiwa, F. O., Adey, A. C., Aft, R., Ahn, K. J., Alikarami, F., Alon, S., Ashenberg, O., Baker, E., Baker, G. J., Bandyopadhyay, S., Bayguinov, P., Beane, J., Becker, W., Bernt, K., Betts, C. B., Bletz, J., Blosser, T., Boire, A., Boland, G. M., Boyden, E. S., Bucher, E., Bueno, R., Cai, Q., Cambuli, F., Campbell, J., Cao, S., Caravan, W., Chaligne, R., Chan, J. M., Chasnoff, S., Chatterjee, D., Chen, A. A., Chen, C., Chen, C., Chen, B., Chen, F., Chen, S., Chheda, M. G., Chin, K., Cho, H., Chun, J., Cisneros, L., Coffey, R. J., Cohen, O., Colditz, G. A., Cole, K. A., Collins, N., Cotter, D., Coussens, L. M., Coy, S., Creason, A. L., Cui, Y., Zhou, D. C., Curtis, C., Davies, S. R., Bruijn, I., Delorey, T. M., Demir, E., Denardo, D., Diep, D., Ding, L., DiPersio, J., Dubinett, S. M., Eberlein, T. J., Eddy, J. A., Esplin, E. D., Factor, R. E., Fatahalian, K., Feiler, H. S., Fernandez, J., Fields, A., Fields, R. C., Fitzpatrick, J. A., Ford, J. M., Franklin, J., Fulton, B., Gaglia, G., Galdieri, L., Ganesh, K., Gao, J., Gaudio, B. L., Getz, G., Gibbs, D. L., Gillanders, W. E., Goecks, J., Goodwin, D., Gray, J. W., Greenleaf, W., Grimm, L. J., Gu, Q., Guerriero, J. L., Guha, T., Guimaraes, A. R., Gutierrez, B., Hacohen, N., Hanson, C. R., Harris, C. R., Hawkins, W. G., Heiser, C. N., Hoffer, J., Hollmann, T. J., Hsieh, J. J., Huang, J., Hunger, S. P., Hwang, E., Iacobuzio-Donahue, C., Iglesia, M. D., Islam, M., Izar, B., Jacobson, C. A., Janes, S., Jayasinghe, R. G., Jeudi, T., Johnson, B. E., Johnson, B. E., Ju, T., Kadara, H., Karnoub, E., Karpova, A., Khan, A., Kibbe, W., Kim, A. H., King, L. M., Kozlowski, E., Krishnamoorthy, P., Krueger, R., Kundaje, A., Ladabaum, U., Laquindanum, R., Lau, C., Lau, K. S., LeBoeuf, N. R., Lee, H., Lenburg, M., Leshchiner, I., Levy, R., Li, Y., Lian, C. G., Liang, W., Lim, K., Lin, Y., Liu, D., Liu, Q., Liu, R., Lo, J., Lo, P., Longabaugh, W. J., Longacre, T., Luckett, K., Ma, C., Maher, C., Maier, A., Makowski, D., Maley, C., Maliga, Z., Manoj, P., Maris, J. M., Markham, N., Marks, J. R., Martinez, D., Mashl, J., Masilionis, I., Massague, J., Mazurowski, M. A., McKinley, E. T., McMichael, J., Meyerson, M., Mills, G. B., Mitri, Z. I., Moorman, A., Mudd, J., Murphy, G. F., Deen, N. N., Navin, N. E., Nawy, T., Ness, R. M., Nevins, S., Nirmal, A. J., Novikov, E., Oh, S. T., Oldridge, D. A., Owzar, K., Pant, S. M., Park, W., Patti, G. J., Paul, K., Pelletier, R., Persson, D., Petty, C., Pfister, H., Polyak, K., Puram, S. V., Qiu, Q., Villalonga, A. Q., Ramirez, M. A., Rashid, R., Reeb, A. N., Reid, M. E., Remsik, J., Riesterer, J. L., Risom, T., Ritch, C. C., Rolong, A., Rudin, C. M., Ryser, M. D., Sato, K., Sears, C. L., Semenov, Y. R., Shen, J., Shoghi, K. I., Shrubsole, M. J., Shyr, Y., Sibley, A. B., Simmons, A. J., Sinha, A., Sivagnanam, S., Song, S., Southar-Smith, A., Spira, A. E., Cyr, J. S., Stefankiewicz, S., Storrs, E. P., Stover, E. H., Strand, S. H., Straub, C., Street, C., Su, T., Surrey, L. F., Suver, C., Tan, K., Terekhanova, N. V., Ternes, L., Thadi, A., Thomas, G., Tibshirani, R., Umeda, S., Uzun, Y., Vallius, T., Van Allen, E. R., Vandekar, S., Vega, P. N., Veis, D. J., Vennam, S., Verma, A., Vigneau, S., Wagle, N., Wahl, R., Walle, T., Wang, L., Warchol, S., Washington, M. K., Watson, C., Weimer, A. K., Wendl, M. C., West, R. B., White, S., Windon, A. L., Wu, H., Wu, C., Wu, Y., Wyczalkowski, M. A., Xu, J., Yao, L., Yu, W., Zhang, K., Zhu, X. 2022; 19 (3): 262-267

    View details for DOI 10.1038/s41592-022-01415-4

    View details for PubMedID 35277708

  • Genome-wide identification of the genetic basis of amyotrophic lateral sclerosis. Neuron Zhang, S., Cooper-Knock, J., Weimer, A. K., Shi, M., Moll, T., Marshall, J. N., Harvey, C., Nezhad, H. G., Franklin, J., Souza, C. D., Ning, K., Wang, C., Li, J., Dilliott, A. A., Farhan, S., Elhaik, E., Pasniceanu, I., Livesey, M. R., Eitan, C., Hornstein, E., Kenna, K. P., Project MinE ALS Sequencing Consortium, Veldink, J. H., Ferraiuolo, L., Shaw, P. J., Snyder, M. P., Blair, I., Wray, N. R., Kiernan, M., Mitne Neto, M., Chio, A., Cauchi, R., Robberecht, W., van Damme, P., Corcia, P., Couratier, P., Hardiman, O., McLaughin, R., Gotkine, M., Drory, V., Ticozzi, N., Silani, V., Veldink, J. H., van den Berg, L. H., de Carvalho, M., Mora Pardina, J. S., Povedano, M., Andersen, P., Weber, M., Basak, N. A., Al-Chalabi, A., Shaw, C., Shaw, P. J., Morrison, K. E., Landers, J. E., Glass, J. D. 1800

    Abstract

    Amyotrophic lateral sclerosis (ALS) is a complex disease that leads to motor neuron death. Despite heritability estimates of 52%, genome-wide association studies (GWASs) have discovered relatively few loci. We developed a machine learning approach called RefMap, which integrates functional genomics with GWAS summary statistics for gene discovery. With transcriptomic and epigenetic profiling of motor neurons derived from induced pluripotent stem cells (iPSCs), RefMap identified 690 ALS-associated genes that represent a 5-fold increase in recovered heritability. Extensive conservation, transcriptome, network, and rare variant analyses demonstrated the functional significance of candidate genes in healthy and diseased motor neurons and brain tissues. Genetic convergence between common and rare variation highlighted KANK1 as a new ALS gene. Reproducing KANK1 patient mutations in human neurons led to neurotoxicity and demonstrated that TDP-43 mislocalization, a hallmark pathology of ALS, is downstream of axonal dysfunction. RefMap can be readily applied to other complex diseases.

    View details for DOI 10.1016/j.neuron.2021.12.019

    View details for PubMedID 35045337

  • Common and rare variant analyses combined with single-cell multiomics reveal cell-type-specific molecular mechanisms of COVID-19 severity. medRxiv : the preprint server for health sciences Zhang, S., Cooper-Knock, J., Weimer, A. K., Harvey, C., Julian, T. H., Wang, C., Li, J., Furini, S., Frullanti, E., Fava, F., Renieri, A., Pan, C., Song, J., Billing-Ross, P., Gao, P., Shen, X., Timpanaro, I. S., Kenna, K. P., VA Million Veteran Program, GEN-COVID Network, Davis, M. M., Tsao, P. S., Snyder, M. P. 2021

    Abstract

    The determinants of severe COVID-19 in non-elderly adults are poorly understood, which limits opportunities for early intervention and treatment. Here we present novel machine learning frameworks for identifying common and rare disease-associated genetic variation, which outperform conventional approaches. By integrating single-cell multiomics profiling of human lungs to link genetic signals to cell-type-specific functions, we have discovered and validated over 1,000 risk genes underlying severe COVID-19 across 19 cell types. Identified risk genes are overexpressed in healthy lungs but relatively downregulated in severely diseased lungs. Genetic risk for severe COVID-19, within both common and rare variants, is particularly enriched in natural killer (NK) cells, which places these immune cells upstream in the pathogenesis of severe disease. Mendelian randomization indicates that failed NKG2D-mediated activation of NK cells leads to critical illness. Network analysis further links multiple pathways associated with NK cell activation, including type-I-interferon-mediated signalling, to severe COVID-19. Our rare variant model, PULSE, enables sensitive prediction of severe disease in non-elderly patients based on whole-exome sequencing; individualized predictions are accurate independent of age and sex, and are consistent across multiple populations and cohorts. Risk stratification based on exome sequencing has the potential to facilitate post-exposure prophylaxis in at-risk individuals, potentially based around augmentation of NK cell function. Overall, our study characterizes a comprehensive genetic landscape of COVID-19 severity and provides novel insights into the molecular mechanisms of severe disease, leading to new therapeutic targets and sensitive detection of at-risk individuals.

    View details for DOI 10.1101/2021.06.15.21258703

    View details for PubMedID 34189540

  • Single-cell resolution of lineage trajectories in the Arabidopsis stomatal lineage and developing leaf. Developmental cell Lopez-Anido, C. B., Vaten, A., Smoot, N. K., Sharma, N., Guo, V., Gong, Y., Anleu Gil, M. X., Weimer, A. K., Bergmann, D. C. 2021; 56 (7): 1043

    Abstract

    Dynamic cell identities underlie flexible developmental programs. The stomatal lineage in the Arabidopsis leaf epidermis features asynchronous and indeterminate divisions that can be modulated by environmental cues. The products of the lineage, stomatal guard cells and pavement cells, regulate plant-atmosphere exchanges, and the epidermis as a whole influences overall leaf growth. How flexibility is encoded in development of the stomatal lineage and how cell fates are coordinated in the leaf are open questions. Here, by leveraging single-cell transcriptomics and molecular genetics, we uncovered models of cell differentiation within Arabidopsis leaf tissue. Profiles across leaf tissues identified points of regulatory congruence. In the stomatal lineage, single-cell resolution resolved underlying cell heterogeneity within early stages and provided a fine-grained profile of guard cell differentiation. Through integration of genome-scale datasets and spatiotemporally precise functional manipulations, we also identified an extended role for the transcriptional regulator SPEECHLESS in reinforcing cell fate commitment.

    View details for DOI 10.1016/j.devcel.2021.03.014

    View details for PubMedID 33823130

  • Lineage- and stage-specific expressed CYCD7;1 coordinates the single symmetric division that creates stomatal guard cells DEVELOPMENT Weimer, A. K., Matos, J. L., Sharma, N., Patell, F., Murray, J. H., Dewitte, W., Bergmann, D. C. 2018; 145 (6)

    View details for DOI 10.1242/dev.160671

    View details for Web of Science ID 000601191000002

  • Specialization of CDK regulation under DNA damage. Cell cycle Weimer, A. K., Biedermann, S., Schnittger, A. 2017; 16 (2): 143-144

    View details for DOI 10.1080/15384101.2016.1235852

    View details for PubMedID 27687239

    View details for PubMedCentralID PMC5283820

  • Phosphorylation of MAP65-1 by Arabidopsis Aurora Kinases Is Required for Efficient Cell Cycle Progression PLANT PHYSIOLOGY Boruc, J., Weimer, A. K., Stoppin-Mellet, V., Mylle, E., Kosetsu, K., Cedeno, C., Jaquinod, M., Njo, M., De Milde, L., Tompa, P., Gonzalez, N., Inze, D., Beeckman, T., Vantard, M., Van Damme, D. 2017; 173 (1): 582-599

    Abstract

    Aurora kinases are key effectors of mitosis. Plant Auroras are functionally divided into two clades. The alpha Auroras (Aurora1 and Aurora2) associate with the spindle and the cell plate and are implicated in controlling formative divisions throughout plant development. The beta Aurora (Aurora3) localizes to centromeres and likely functions in chromosome separation. In contrast to the wealth of data available on the role of Aurora in other kingdoms, knowledge on their function in plants is merely emerging. This is exemplified by the fact that only histone H3 and the plant homolog of TPX2 have been identified as Aurora substrates in plants. Here we provide biochemical, genetic, and cell biological evidence that the microtubule-bundling protein MAP65-1-a member of the MAP65/Ase1/PRC1 protein family, implicated in central spindle formation and cytokinesis in animals, yeasts, and plants-is a genuine substrate of alpha Aurora kinases. MAP65-1 interacts with Aurora1 in vivo and is phosphorylated on two residues at its unfolded tail domain. Its overexpression and down-regulation antagonistically affect the alpha Aurora double mutant phenotypes. Phospho-mutant analysis shows that Aurora contributes to the microtubule bundling capacity of MAP65-1 in concert with other mitotic kinases.

    View details for DOI 10.1104/pp.16.01602

    View details for Web of Science ID 000394135800043

    View details for PubMedID 27879390

  • The plant-specific CDKB1-CYCB1 complex mediates homologous recombination repair in Arabidopsis EMBO JOURNAL Weimer, A. K., Biedermann, S., Harashima, H., Roodbarkelari, F., Takahashi, N., Foreman, J., Guan, Y., Pochon, G., Heese, M., van Damme, D., Sugimoto, K., Koncz, C., Doerner, P., Umeda, M., Schnittger, A. 2016; 35 (19): 2068-2086

    Abstract

    Upon DNA damage, cyclin-dependent kinases (CDKs) are typically inhibited to block cell division. In many organisms, however, it has been found that CDK activity is required for DNA repair, especially for homology-dependent repair (HR), resulting in the conundrum how mitotic arrest and repair can be reconciled. Here, we show that Arabidopsis thaliana solves this dilemma by a division of labor strategy. We identify the plant-specific B1-type CDKs (CDKB1s) and the class of B1-type cyclins (CYCB1s) as major regulators of HR in plants. We find that RADIATION SENSITIVE 51 (RAD51), a core mediator of HR, is a substrate of CDKB1-CYCB1 complexes. Conversely, mutants in CDKB1 and CYCB1 fail to recruit RAD51 to damaged DNA CYCB1;1 is specifically activated after DNA damage and we show that this activation is directly controlled by SUPPRESSOR OF GAMMA RESPONSE 1 (SOG1), a transcription factor that acts similarly to p53 in animals. Thus, while the major mitotic cell-cycle activity is blocked after DNA damage, CDKB1-CYCB1 complexes are specifically activated to mediate HR.

    View details for DOI 10.15252/embj.201593083

    View details for Web of Science ID 000385707500004

    View details for PubMedID 27497297

    View details for PubMedCentralID PMC5048351

  • Aurora Kinases Throughout Plant Developoment TRENDS IN PLANT SCIENCE Weimer, A. K., Demidov, D., Lermontova, I., Beeckman, T., Van Damme, D. 2016; 21 (1): 69-79

    Abstract

    Aurora kinases are evolutionarily conserved key mitotic determinants in all eukaryotes. Yeasts contain a single Aurora kinase, whereas multicellular eukaryotes have at least two functionally diverged members. The involvement of Aurora kinases in human cancers has provided an in-depth mechanistic understanding of their roles throughout cell division in animal and yeast models. By contrast, understanding Aurora kinase function in plants is only starting to emerge. Nevertheless, genetic, cell biological, and biochemical approaches have revealed functional diversification between the plant Aurora kinases and suggest a role in formative (asymmetric) divisions, chromatin modification, and genome stability. This review provides an overview of the accumulated knowledge on the function of plant Aurora kinases as well as some major challenges for the future.

    View details for DOI 10.1016/j.tplants.2015.10.001

    View details for Web of Science ID 000369199200010

    View details for PubMedID 26616196

  • RETINOBLASTOMA RELATED1 Regulates Asymmetric Cell Divisions in Arabidopsis PLANT CELL Weimer, A. K., Nowack, M. K., Bouyer, D., Zhao, X., Harashima, H., Naseer, S., De Winter, F., Dissmeyer, N., Geldner, N., Schnittger, A. 2012; 24 (10): 4083-4095

    Abstract

    Formative, also called asymmetric, cell divisions produce daughter cells with different identities. Like other divisions, formative divisions rely first of all on the cell cycle machinery with centrally acting cyclin-dependent kinases (CDKs) and their cyclin partners to control progression through the cell cycle. However, it is still largely obscure how developmental cues are translated at the cellular level to promote asymmetric divisions. Here, we show that formative divisions in the shoot and root of the flowering plant Arabidopsis thaliana are controlled by a common mechanism that relies on the activity level of the Cdk1 homolog CDKA;1, with medium levels being sufficient for symmetric divisions but high levels being required for formative divisions. We reveal that the function of CDKA;1 in asymmetric cell divisions operates through a transcriptional regulation system that is mediated by the Arabidopsis Retinoblastoma homolog RBR1. RBR1 regulates not only cell cycle genes, but also, independent of the cell cycle transcription factor E2F, genes required for formative divisions and cell fate acquisition, thus directly linking cell proliferation with differentiation. This mechanism allows the implementation of spatial information, in the form of high kinase activity, with intracellular gating of developmental decisions.

    View details for DOI 10.1105/tpc.112.104620

    View details for Web of Science ID 000312378300017

    View details for PubMedID 23104828

    View details for PubMedCentralID PMC3517237

  • A General G1/S-Phase Cell-Cycle Control Module in the Flowering Plant Arabidopsis thaliana PLOS GENETICS Zhao, X., Harashima, H., Dissmeyer, N., Pusch, S., Weimer, A. K., Bramsiepe, J., Bouyer, D., Rademacher, S., Nowack, M. K., Novak, B., Sprunck, S., Schnittger, A. 2012; 8 (8)

    Abstract

    The decision to replicate its DNA is of crucial importance for every cell and, in many organisms, is decisive for the progression through the entire cell cycle. A comparison of animals versus yeast has shown that, although most of the involved cell-cycle regulators are divergent in both clades, they fulfill a similar role and the overall network topology of G1/S regulation is highly conserved. Using germline development as a model system, we identified a regulatory cascade controlling entry into S phase in the flowering plant Arabidopsis thaliana, which, as a member of the Plantae supergroup, is phylogenetically only distantly related to Opisthokonts such as yeast and animals. This module comprises the Arabidopsis homologs of the animal transcription factor E2F, the plant homolog of the animal transcriptional repressor Retinoblastoma (Rb)-related 1 (RBR1), the plant-specific F-box protein F-BOX-LIKE 17 (FBL17), the plant specific cyclin-dependent kinase (CDK) inhibitors KRPs, as well as CDKA;1, the plant homolog of the yeast and animal Cdc2⁺/Cdk1 kinases. Our data show that the principle of a double negative wiring of Rb proteins is highly conserved, likely representing a universal mechanism in eukaryotic cell-cycle control. However, this negative feedback of Rb proteins is differently implemented in plants as it is brought about through a quadruple negative regulation centered around the F-box protein FBL17 that mediates the degradation of CDK inhibitors but is itself directly repressed by Rb. Biomathematical simulations and subsequent experimental confirmation of computational predictions revealed that this regulatory circuit can give rise to hysteresis highlighting the here identified dosage sensitivity of CDK inhibitors in this network.

    View details for DOI 10.1371/journal.pgen.1002847

    View details for Web of Science ID 000308529300011

    View details for PubMedID 22879821

    View details for PubMedCentralID PMC3410867

  • Genetic Framework of Cyclin-Dependent Kinase Function in Arabidopsis DEVELOPMENTAL CELL Nowack, M. K., Harashima, H., Dissmeyer, N., Zhao, X., Bouyer, D., Weimer, A. K., De Winter, F., Yang, F., Schnittger, A. 2012; 22 (5): 1030-1040

    Abstract

    Cyclin-dependent kinases (CDKs) are at the heart of eukaryotic cell-cycle control. The yeast Cdc2/CDC28 PSTAIRE kinase and its orthologs such as the mammalian Cdk1 have been found to be indispensable for cell-cycle progression in all eukaryotes investigated so far. CDKA;1 is the only PSTAIRE kinase in the flowering plant Arabidopsis and can rescue Cdc2/CDC28 mutants. Here, we show that cdka;1 null mutants are viable but display specific cell-cycle and developmental defects, e.g., in S phase entry and stem cell maintenance. We unravel that the crucial function of CDKA;1 is the control of the plant Retinoblastoma homolog RBR1 and that codepletion of RBR1 and CDKA;1 rescued most defects of cdka;1 mutants. Our work further revealed a basic cell-cycle control system relying on two plant-specific B1-type CDKs, and the triple cdk mutants displayed an early germline arrest. Taken together, our data indicate divergent functional differentiation of Cdc2-type kinases during eukaryote evolution.

    View details for DOI 10.1016/j.devcel.2012.02.015

    View details for Web of Science ID 000304291700015

    View details for PubMedID 22595674

  • The Arabidopsis thaliana Checkpoint Kinase WEE1 Protects against Premature Vascular Differentiation during Replication Stress PLANT CELL Cools, T., Iantcheva, A., Weimer, A. K., Boens, S., Takahashi, N., Maes, S., Van Den Daele, H., Van Isterdael, G., Schnittger, A., De Veylder, L. 2011; 23 (4): 1435-1448

    Abstract

    A sessile lifestyle forces plants to respond promptly to factors that affect their genomic integrity. Therefore, plants have developed checkpoint mechanisms to arrest cell cycle progression upon the occurrence of DNA stress, allowing the DNA to be repaired before onset of division. Previously, the WEE1 kinase had been demonstrated to be essential for delaying progression through the cell cycle in the presence of replication-inhibitory drugs, such as hydroxyurea. To understand the severe growth arrest of WEE1-deficient plants treated with hydroxyurea, a transcriptomics analysis was performed, indicating prolonged S-phase duration. A role for WEE1 during S phase was substantiated by its specific accumulation in replicating nuclei that suffered from DNA stress. Besides an extended replication phase, WEE1 knockout plants accumulated dead cells that were associated with premature vascular differentiation. Correspondingly, plants without functional WEE1 ectopically expressed the vascular differentiation marker VND7, and their vascular development was aberrant. We conclude that the growth arrest of WEE1-deficient plants is due to an extended cell cycle duration in combination with a premature onset of vascular cell differentiation. The latter implies that the plant WEE1 kinase acquired an indirect developmental function that is important for meristem maintenance upon replication stress.

    View details for DOI 10.1105/tpc.110.082768

    View details for Web of Science ID 000291000500022

    View details for PubMedID 21498679

    View details for PubMedCentralID PMC3101530

  • The regulatory network of cell-cycle progression is fundamentally different in plants versus yeast or metazoans. Plant signaling & behavior Dissmeyer, N., Weimer, A. K., De Veylder, L., Novak, B., Schnittger, A. 2010; 5 (12): 1613-1618

    Abstract

    Plant growth and proliferation control is coming into a global focus due to recent ecological and economical developments. Plants represent not only the largest food supply for mankind but also may serve as a global source of renewable energies. However, plant breeding has to accomplish a tremendous boost in yield to match the growing demand of a still rapidly increasing human population. Moreover, breeding has to adjust to changing environmental conditions, in particular increased drought. Regulation of cell-cycle control is a major determinant of plant growth and therefore an obvious target for plant breeding. Furthermore, cell-cycle control is also crucial for the DNA damage response, for instance upon irradiation. Thus, an in-depth understanding of plant cell-cycle regulation is of importance beyond a scientific point of view. The mere presence of many conserved core cell-cycle regulators, e.g. CDKs, cyclins, or CDK inhibitors, has formed the idea that the cell cycle in plants is exactly or at least very similarly controlled as in yeast or human cells. Here together with a recent publication we demonstrate that this dogma is not true and show that the control of entry into mitosis is fundamentally different in plants versus yeast or metazoans. Our findings build an important base for the understanding and ultimate modulation of plant growth not only during unperturbed but also under harsh environmental conditions.

    View details for PubMedID 21139435

    View details for PubMedCentralID PMC3115114

  • Control of Cell Proliferation, Organ Growth, and DNA Damage Response Operate Independently of Dephosphorylation of the Arabidopsis Cdk1 Homolog CDKA;1 PLANT CELL Dissmeyer, N., Weimer, A. K., Pusch, S., De Schutter, K., Kamei, C. L., Nowack, M. K., Novak, B., Duan, G., Zhu, Y., De Veylder, L., Schnittger, A. 2009; 21 (11): 3641-3654

    Abstract

    Entry into mitosis is universally controlled by cyclin-dependent kinases (CDKs). A key regulatory event in metazoans and fission yeast is CDK activation by the removal of inhibitory phosphate groups in the ATP binding pocket catalyzed by Cdc25 phosphatases. In contrast with other multicellular organisms, we show here that in the flowering plant Arabidopsis thaliana, cell cycle control does not depend on sudden changes in the phosphorylation pattern of the PSTAIRE-containing Cdk1 homolog CDKA;1. Consistently, we found that neither mutants in a previously identified CDC25 candidate gene nor plants in which it is overexpressed display cell cycle defects. Inhibitory phosphorylation of CDKs is also the key event in metazoans to arrest cell cycle progression upon DNA damage. However, we show here that the DNA damage checkpoint in Arabidopsis can also operate independently of the phosphorylation of CDKA;1. These observations reveal a surprising degree of divergence in the circuitry of highly conserved core cell cycle regulators in multicellular organisms. Based on biomathematical simulations, we propose a plant-specific model of how progression through the cell cycle could be wired in Arabidopsis.

    View details for DOI 10.1105/tpc.109.070417

    View details for Web of Science ID 000273235600020

    View details for PubMedID 19948791

    View details for PubMedCentralID PMC2798325