4 results on '"Knapp, Barbara"'
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2. An organelle-specific protein landscape identifies novel diseases and molecular mechanisms
- Author
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Boldt, Karsten, van Reeuwijk, Jeroen, Dougherty, Gerard, Lamers, Ideke J C, Coene, Karlien L M, Arts, Heleen H, Betts, Matthew J, Beyer, Tina, Bolat, Emine, Gloeckner, Christian Johannes, Haidari, Khatera, Hetterschijt, Lisette, Lu, Qianhao, Iaconis, Daniela, Jenkins, Dagan, Klose, Franziska, Knapp, Barbara, Latour, Brooke, Letteboer, Stef J F, Marcelis, Carlo L, Mitic, Dragana, Morleo, Manuela, Oud, Machteld M, Koutroumpas, Konstantinos, Riemersma, Moniek, Rix, Susan, Terhal, Paulien A, Toedt, Grischa, van Dam, Teunis J P, de Vrieze, Erik, Wissinger, Yasmin, Wu, Ka Man, Apic, Gordana, Beales, Philip L, Nguyen, Thanh-Minh T, Blacque, Oliver E, Gibson, Toby J, Huynen, Martijn A, Katsanis, Nicholas, Kremer, Hannie, Omran, Heymut, van Wijk, Erwin, Wolfrum, Uwe, Kepes, François, Davis, Erica E, Texier, Yves, Franco, Brunella, Giles, Rachel H, Ueffing, Marius, Russell, Robert B, Roepman, Ronald, Group, UK10K Rare Diseases, Al-Turki, Saeed, Anderson, Carl, Antony, Dinu, Barroso, Inês, van Beersum, Sylvia E C, Bentham, Jamie, Bhattacharya, Shoumo, Carss, Keren, Chatterjee, Krishna, Cirak, Sebahattin, Cosgrove, Catherine, Danecek, Petr, Durbin, Richard, Fitzpatrick, David, Floyd, Jamie, Horn, Nicola, Reghan Foley, A., Franklin, Chris, Futema, Marta, Humphries, Steve E, Hurles, Matt, Joyce, Chris, McCarthy, Shane, Mitchison, Hannah M, Muddyman, Dawn, Muntoni, Francesco, Willer, Jason R, O'Rahilly, Stephen, Onoufriadis, Alexandros, Payne, Felicity, Plagnol, Vincent, Raymond, Lucy, Savage, David B, Scambler, Peter, Schmidts, Miriam, Schoenmakers, Nadia, Semple, Robert, Mans, Dorus A, Serra, Eva, Stalker, Jim, van Kogelenberg, Margriet, Vijayarangakannan, Parthiban, Walter, Klaudia, Whittall, Ros, Williamson, Kathy, Boldt, K, van Reeuwijk, J, Lu, Q, Koutroumpas, K, Nguyen, Tmt, Texier, Y, van Beersum, Sec, Horn, N, Willer, Jr, Mans, Da, Dougherty, G, Lamers, Ijc, Coene, Klm, Arts, Hh, Betts, Mj, Beyer, T, Bolat, E, Gloeckner, Cj, Haidari, K, Hetterschijt, L, Iaconis, D, Jenkins, D, Klose, F, Knapp, B, Latour, B, Letteboer, Sjf, Marcelis, Cl, Mitic, D, Morleo, M, Oud, Mm, Riemersma, M, Rix, S, Terhal, Pa, Toedt, G, van Dam, Tjp, de Vrieze, E, Wissinger, Y, Wu, Km, Apic, G, Beales, Pl, Blacque, Oe, Gibson, Tj, Huynen, Ma, Katsanis, N, Kremer, H, Omran, H, van Wijk, E, Wolfrum, U, Kepes, F, Davis, Ee, Franco, B, Giles, Rh, Ueffing, M, Russell, Rb, Roepman, R, Boldt, Karsten, Van Reeuwijk, Jeroen, Lu, Qianhao, Koutroumpas, Konstantino, Nguyen, Thanh Minh T., Texier, Yve, Van Beersum, Sylvia E. C., Horn, Nicola, Willer, Jason R., Mans, Dorus A., Dougherty, Gerard, Lamers, Ideke J. C., Coene, Karlien L. M., Arts, Heleen H., Betts, Matthew J., Beyer, Tina, Bolat, Emine, Gloeckner, Christian Johanne, Haidari, Khatera, Hetterschijt, Lisette, Iaconis, Daniela, Jenkins, Dagan, Klose, Franziska, Knapp, Barbara, Latour, Brooke, Letteboer, Stef J. F., Marcelis, Carlo L., Mitic, Dragana, Morleo, Manuela, Oud, Machteld M., Riemersma, Moniek, Rix, Susan, Terhal, Paulien A., Toedt, Grischa, Van Dam, Teunis J. P., De Vrieze, Erik, Wissinger, Yasmin, Wu, Ka Man, Al Turki, Saeed, Anderson, Carl, Antony, Dinu, Barroso, Inê, Bentham, Jamie, Bhattacharya, Shoumo, Carss, Keren, Chatterjee, Krishna, Cirak, Sebahattin, Cosgrove, Catherine, Danecek, Petr, Durbin, Richard, Fitzpatrick, David, Floyd, Jamie, Foley, A. Reghan, Franklin, Chri, Futema, Marta, Humphries, Steve E., Hurles, Matt, Joyce, Chri, Mccarthy, Shane, Mitchison, Hannah M., Muddyman, Dawn, Muntoni, Francesco, O'Rahilly, Stephen, Onoufriadis, Alexandro, Payne, Felicity, Plagnol, Vincent, Raymond, Lucy, Savage, David B., Scambler, Peter, Schmidts, Miriam, Schoenmakers, Nadia, Semple, Robert, Serra, Eva, Stalker, Jim, Van Kogelenberg, Margriet, Vijayarangakannan, Parthiban, Walter, Klaudia, Whittall, Ro, Williamson, Kathy, Apic, Gordana, Beales, Philip L., Blacque, Oliver E., Gibson, Toby J., Huynen, Martijn A., Katsanis, Nichola, Kremer, Hannie, Omran, Heymut, Van Wijk, Erwin, Wolfrum, Uwe, Kepes, Françoi, Davis, Erica E., Franco, Brunella, Giles, Rachel H., Ueffing, Mariu, Russell, Robert B., and Roepman, Ronald
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Proteomics ,0301 basic medicine ,Systems Analysis ,DNA Mutational Analysis ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,General Physics and Astronomy ,Datasets as Topic ,methods [Chromatography, Affinity] ,Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12] ,Chromatography, Affinity ,Mass Spectrometry ,Protein Interaction Mapping ,therapy [Ciliopathies] ,genetics [Ciliopathies] ,methods [Molecular Targeted Therapy] ,Molecular Targeted Therapy ,Protein Interaction Maps ,Multidisciplinary ,Cilium ,Chemistry (all) ,abnormalities [Spine] ,pathology [Ciliopathies] ,genetics [Muscle Hypotonia] ,therapy [Muscle Hypotonia] ,Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] ,metabolism [Proteins] ,isolation & purification [Proteins] ,physiology [Biological Transport] ,3. Good health ,Cell biology ,Vesicular transport protein ,pathology [Dwarfism] ,metabolism [Cilia] ,Muscle Hypotonia ,ddc:500 ,pathology [Muscle Hypotonia] ,pathology [Spine] ,genetics [Dwarfism] ,Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] ,Science ,Dwarfism ,Exocyst ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,Physics and Astronomy (all) ,03 medical and health sciences ,Intraflagellar transport ,Ciliogenesis ,Organelle ,Humans ,Cilia ,Biochemistry, Genetics and Molecular Biology (all) ,Proteins ,Biological Transport ,General Chemistry ,therapy [Dwarfism] ,Fibroblasts ,genetics [Proteins] ,Ciliopathies ,Spine ,methods [Protein Interaction Mapping] ,Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] ,030104 developmental biology ,Proteostasis ,HEK293 Cells ,methods [Proteomics] - Abstract
Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred and seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions and 52 complexes. Reverse tagging, repetition of purifications and statistical analyses, produce a high-resolution network that reveals organelle-specific interactions and complexes not apparent in larger studies, and links vesicle transport, the cytoskeleton, signalling and ubiquitination to ciliary signalling and proteostasis. We observe sub-complexes in exocyst and intraflagellar transport complexes, which we validate biochemically, and by probing structurally predicted, disruptive, genetic variants from ciliary disease patients. The landscape suggests other genetic diseases could be ciliary including 3M syndrome. We show that 3M genes are involved in ciliogenesis, and that patient fibroblasts lack cilia. Overall, this organelle-specific targeting strategy shows considerable promise for Systems Medicine., Mutations in proteins that localize to primary cilia cause devastating diseases, yet the primary cilium is a poorly understood organelle. Here the authors use interaction proteomics to identify a network of human ciliary proteins that provides new insights into several biological processes and diseases.
- Published
- 2016
3. CiliaCarta: An integrated and validated compendium of ciliary genes.
- Author
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van Dam, Teunis J. P., Kennedy, Julie, van der Lee, Robin, de Vrieze, Erik, Wunderlich, Kirsten A., Rix, Suzanne, Dougherty, Gerard W., Lambacher, Nils J., Li, Chunmei, Jensen, Victor L., Leroux, Michel R., Hjeij, Rim, Horn, Nicola, Texier, Yves, Wissinger, Yasmin, van Reeuwijk, Jeroen, Wheway, Gabrielle, Knapp, Barbara, Scheel, Jan F., and Franco, Brunella
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CILIA & ciliary motion ,DEVELOPMENTAL biology ,CYTOLOGY ,GENES ,LIFE sciences ,OUTLINES - Abstract
The cilium is an essential organelle at the surface of mammalian cells whose dysfunction causes a wide range of genetic diseases collectively called ciliopathies. The current rate at which new ciliopathy genes are identified suggests that many ciliary components remain undiscovered. We generated and rigorously analyzed genomic, proteomic, transcriptomic and evolutionary data and systematically integrated these using Bayesian statistics into a predictive score for ciliary function. This resulted in 285 candidate ciliary genes. We generated independent experimental evidence of ciliary associations for 24 out of 36 analyzed candidate proteins using multiple cell and animal model systems (mouse, zebrafish and nematode) and techniques. For example, we show that OSCP1, which has previously been implicated in two distinct non-ciliary processes, causes ciliogenic and ciliopathy-associated tissue phenotypes when depleted in zebrafish. The candidate list forms the basis of CiliaCarta, a comprehensive ciliary compendium covering 956 genes. The resource can be used to objectively prioritize candidate genes in whole exome or genome sequencing of ciliopathy patients and can be accessed at . [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
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4. CiliaCarta: An integrated and validated compendium of ciliary genes
- Author
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Gerard W. Dougherty, Victor L. Jensen, Jan Frederik Scheel, Katarzyna Szymanska, Uwe Wolfrum, Radek Szklarczyk, Miriam Schmidts, Julie Kennedy, Erwin van Wijk, Brunella Franco, Toby J. Gibson, Machteld M. Oud, Chunmei Li, Nils J. Lambacher, Erik de Vrieze, Grischa Toedt, Teunis J. P. van Dam, Karsten Boldt, Heymut Omran, Yves Texier, Rachel H. Giles, Ronald Roepman, Kirsten A. Wunderlich, Sylvia E. C. van Beersum, Oliver E. Blacque, Thanh-Minh T. Nguyen, Konstantinos Koutroumpas, Hannie Kremer, Nicola Horn, Martijn A. Huynen, Michel R. Leroux, Gabrielle Wheway, Rim Hjeij, Philip L. Beales, Gisela G. Slaats, Robert B. Russell, Robin van der Lee, François Képès, Yasmin Wissinger, Barbara Knapp, Dorus A. Mans, Suzanne Rix, Marius Ueffing, Colin A. Johnson, Stef J.F. Letteboer, Victor Hernandez-Hernandez, Qianhao Lu, Jeroen van Reeuwijk, Sub Bioinformatics, Theoretical Biology and Bioinformatics, MUMC+: DA KG Lab Centraal Lab (9), Klinische Genetica, RS: GROW - R4 - Reproductive and Perinatal Medicine, van Dam, Teunis J P, Kennedy, Julie, van der Lee, Robin, de Vrieze, Erik, Wunderlich, Kirsten A, Rix, Suzanne, Dougherty, Gerard W, Lambacher, Nils J, Li, Chunmei, Jensen, Victor L, Leroux, Michel R, Hjeij, Rim, Horn, Nicola, Texier, Yve, Wissinger, Yasmin, van Reeuwijk, Jeroen, Wheway, Gabrielle, Knapp, Barbara, Scheel, Jan F, Franco, Brunella, Mans, Dorus A, van Wijk, Erwin, Képès, Françoi, Slaats, Gisela G, Toedt, Grischa, Kremer, Hannie, Omran, Heymut, Szymanska, Katarzyna, Koutroumpas, Konstantino, Ueffing, Mariu, Nguyen, Thanh-Minh T, Letteboer, Stef J F, Oud, Machteld M, van Beersum, Sylvia E C, Schmidts, Miriam, Beales, Philip L, Lu, Qianhao, Giles, Rachel H, Szklarczyk, Radek, Russell, Robert B, Gibson, Toby J, Johnson, Colin A, Blacque, Oliver E, Wolfrum, Uwe, Boldt, Karsten, Roepman, Ronald, Hernandez-Hernandez, Victor, and Huynen, Martijn A
- Subjects
Proteomics ,Sensory Receptors ,Nematoda ,Social Sciences ,Ciliopathies ,Biochemistry ,Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12] ,Transcriptome ,0302 clinical medicine ,Animal Cells ,Psychology ,RETINAL PHOTORECEPTOR CELLS ,Exome ,Neurons ,0303 health sciences ,030302 biochemistry & molecular biology ,Eukaryota ,Genomics ,PRIMARY CILIUM ,thecilium ,3. Good health ,Nucleic acids ,Genetic interference ,Osteichthyes ,Medicine ,Epigenetics ,Cellular Structures and Organelles ,Cellular Types ,proteomic databases ,Sensory Receptor Cells ,Science ,education ,Ciliary genes ,LEBER CONGENITAL AMAUROSIS ,03 medical and health sciences ,Genetics ,Cilia ,Caenorhabditis elegans ,IDENTIFICATION ,MUTATIONS ,Embryos ,cilia ,Organisms ,Biology and Life Sciences ,Bayes Theorem ,Molecular Sequence Annotation ,medicine.disease ,Invertebrates ,Fish ,ciliary proteome ,Animal Studies ,Caenorhabditis ,Gene expression ,embryos ,030217 neurology & neurosurgery ,Developmental Biology ,Neuroscience ,Photoreceptors ,Candidate gene ,Embryology ,Oligonucleotides ,Morpholino ,Database and Informatics Methods ,RNA interference ,Bayesian classifier ,TRANSITION ZONE ,Zebrafish ,Antisense Oligonucleotides ,Multidisciplinary ,Spectrometric Identification of Proteins ,Proteomic Databases ,Nucleotides ,Cilium ,Stable Isotope Labeling by Amino Acids in Cell Culture ,photoreceptors ,Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] ,Animal Models ,Phenotype ,INTRAFLAGELLAR TRANSPORT ,DIFFERENTIATION ,Experimental Organism Systems ,Caenorhabditis Elegans ,Vertebrates ,Sensory Perception ,Research Article ,Signal Transduction ,EXPRESSION ,Stable isotope labeling by amino acids in cell culture ,Computational biology ,Biology ,Research and Analysis Methods ,SOLUTE-CARRIER-PROTEIN ,Model Organisms ,medicine ,Animals ,data integration ,030304 developmental biology ,Afferent Neurons ,Reproducibility of Results ,Cell Biology ,zebrafish ,biology.organism_classification ,Ciliopathy ,Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] ,Biological Databases ,Cellular Neuroscience ,RNA ,OSCP1 ,CiliaCarta - Abstract
The cilium is an essential organelle at the surface of mammalian cells whose dysfunction causes a wide range of genetic diseases collectively called ciliopathies. The current rate at which new ciliopathy genes are identified suggests that many ciliary components remain undiscovered. We generated and rigorously analyzed genomic, proteomic, transcriptomic and evolutionary data and systematically integrated these using Bayesian statistics into a predictive score for ciliary function. This resulted in 285 candidate ciliary genes. We generated independent experimental evidence of ciliary associations for 24 out of 36 analyzed candidate proteins using multiple cell and animal model systems (mouse, zebrafish and nematode) and techniques. For example, we show that OSCP1, which has previously been implicated in two distinct non-ciliary processes, causes ciliogenic and ciliopathy-associated tissue phenotypes when depleted in zebrafish. The candidate list forms the basis of CiliaCarta, a comprehensive ciliary compendium covering 956 genes. The resource can be used to objectively prioritize candidate genes in whole exome or genome sequencing of ciliopathy patients and can be accessed at http://bioinformatics.bio.uu.nl/john/syscilia/ciliacarta/. This work was supported by the European Community’s Seventh Framework Programme [241955, 278568 to MU and KB, 602273 to RS]; the Virgo consortium, funded by the Dutch government [FES0908 to TvD, RvdL and MAH]; the Netherlands Genomics Initiative [050-060-452 to TvD, RvdL and MAH]; the Canadian Institutes of Health Research [MOP-142243, MOP-82870 and PJT-156042 to MRL]; Michael Smith Foundation for Health Research to MRL and VLJ; Kidney Research Scientist Core Education and National Training fellowship to VLJ; The Foundation Fighting Blindness [PPA-0717-0719-RAD to UW, RR, and MU]; the Dutch Kidney Foundation “KOUNCIL” consortium [CP11.18 to RHG, PLB and RR]; The Deutsche Forschungsgemeinschaft [Excellence grant CellNetworks to RBR and QL, CRC1140 “Kidney Disease – From Genes to Mechanisms” to MS, collaborative research center grant SFB-1411 KIDGEM to MS]; Metakids Foundation to RS; the National Institute for Health Research to PLB and VH-H. PLB is an NIHR Senior Investigator; Radboudumc Hypatia Tenure Track Fellowship, Radboud Universiteit excellence fellowship, ERC starting grant TREATCilia, grant agreement no. 716344 to MS; and the Netherlands Organization for Scientific Research [NWO Vici-865.12.005 to RR].
- Published
- 2019
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