Research Groups

Molecular Neurobiology of Ageing

The accumulation of aggregation-prone disease proteins in aggregates in the brain is the major pathological hallmark of several age-related neurodegenerative disorders, including Alzheimer’s and Parkinson’s disease. To understand disease mechanisms, the group led by Ellen Nollen aims to uncover the cellular pathways that regulate disease-protein toxicity, aggregation, and spreading.

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  • Ellen Nollen Visit

    Group Leader of the Laboratory of Molecular Neurobiology of Ageing

    Research fields

    Protein aggregation, neurodegeneration, ageing, c. elegans

    Postdoctoral Fellows
    Anna Ainslie Castellanos
    Eugenia Goya
    PhD Students
    Lale Gungordu
    Suzanne Couzijn
    Renée Seinstra
  • To identify cellular pathways and better understand the molecular function of regulators of age-related protein aggregation, toxicity, and spreading, the group is combining the power of C. elegans genetics with the development of cell-biological and biochemical tools to monitor aggregation, toxicity, and cell-to-cell transmission of aggregation-prone proteins in living worms. Nollen’s team aims to translate findings in worms to mice and patient-derived cells. Their studies will provide new mechanistic insights into how human cells cope with protein damage in health, aging and disease.

    • Perni M, Challa PK, Kirkegaard JB, Limbocker R, Koopman M, Hardenberg MC, Sormanni P, Müller T, Saar KL, Roode LWY, Habchi J, Vecchi G, Fernando N, Casford S, Nollen EAA, Vendruscolo M, Dobson CM, Knowles TPJ. (2018). Massively parallel C. elegans tracking provides multi-dimensional fingerprints for phenotypic discovery. Journal of Neuroscience Methods.  
    • Koopman M, Peter Q, Seinstra RI, Perni M, Vendruscolo M, Dobson CM, Knowles TPJ, Nollen EAA (2020) Assessing motor-related phenotypes of Caenorhabditis elegans with the wide field-of-view nematode tracking platform. Nature Protocols.  
    • Koopman M, Hetz C, Nollen EAA (2019) Saved by the Matrix: UPR Independent Survival under ER Stress. Cell.
    • Sorgdrager FJH, Naudé PJW, Kema IP, Nollen EA, Deyn PP. (2019) Tryptophan Metabolism in Inflammaging: From Biomarker to Therapeutic Target. Frontier Immunology.  
    • Sorgdrager FJH, Vermeiren Y, Van Faassen M, van der Ley C, Nollen EAA, Kema IP, De Deyn PP (2019) Age- and disease-specific changes of the kynurenine pathway in Parkinson's and Alzheimer's disease. Journal of Neurochemistry
    • Laine RF, Sinnige T, Ma KY, Haack AJ, Poudel C, Gaida P, Curry N, Perni M, Nollen EAA, Dobson CM, Vendruscolo M, Kaminski Schierle GS, Kaminski CF (2019) Fast Fluorescence Lifetime Imaging Reveals the Aggregation Processes of α-Synuclein and Polyglutamine in Aging Caenorhabditis elegans. ACS Chemical Biology.  
    • Janssens GE, Lin XX, Millan-Ariño L, Kavšek A, Sen I, Seinstra RI, Stroustrup N, Nollen EAA, Riedel CG. (2019) Transcriptomics-Based Screening Identifies Pharmacological Inhibition of Hsp90 as a Means to Defer Aging. Cell Reports.
    • Koopman M, Seinstra RI, Nollen EAA.(2019) C. elegans as a Model for Synucleinopathies and Other Neurodegenerative Diseases: Tools and Techniques. Methods in Molecular Biology.  
    • Platten M, Nollen EAA, Röhrig UF, Fallarino F, Opitz CA. (2019) Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond. Nature review Drug Discovery.
    • Perni M, Casford S, Aprile FA, Nollen EA, Knowles TPJ, Vendruscolo M, Dobson CM. (2018). Automated Behavioral Analysis of Large C. elegans Populations Using a Wide Field-of-view Tracking Platform. Journal of Visualized Experiments.
    • Javer A, Currie M, Lee CW, Hokanson J, Li K, Martineau CN, Yemini E, Grundy LJ, Li C, Ch'ng Q, Schafer WR, Nollen EAA, Kerr R, Brown AEX. (2018) An open-source platform for analyzing and sharing worm-behavior data. Nature Methods.
    • Mata-Cabana A, Sin O, Seinstra RI and Nollen EA. (2018). Nuclear/Cytoplasmic Fractionation of Proteins from Caenorhabditis elegans. Bio-protocol    
    • Sin O, Mata-Cabana A, Seinstra RI and Nollen EA.(2018). Filter Retardation Assay for Detecting and Quantifying Polyglutamine Aggregates Using Caenorhabditis elegans Lysates. Bio-protocol  
    • Perni M, Flagmeier P, Limbocker R, Cascella R, Aprile FA, Galvagnion C, Heller GT, Meisl G, Chen SW, Kumita JR, Challa PK, Kirkegaard JB, Cohen SIA, Mannini B, Barbut D, Nollen EAA, Cecchi C, Cremades N, Knowles TPJ, Chiti F, Zasloff M, Vendruscolo M, Dobson CM. Multistep Inhibition of α-Synuclein Aggregation and Toxicity in Vitro and in Vivo by Trodusquemine.(2018) ACS Chemical Biology.  
    • Yoshimura Y, Holmberg MA, Kukic P, Andersen CB, Mata-Cabana A, Falsone SF, Vendruscolo M, Nollen EAA, Mulder FAA.(2017) MOAG-4 promotes the aggregation of α-synuclein by competing with self-protective electrostatic interactions. Journal of Biological Chemistry.
    • Sin O, de Jong T, Kudron M , Zaini A , Aprile FA , Seinstra R, Mata-Cabana A, Stroo E, Willinge Prins R, Martineau C, Wang HH, Hogewerf W, Steinhof A, Wanker EE, Vendruscolo M, Calkhoven CF, Reinke V, Guryev V, Nollen EAA. (2017) Identification of an RNA Pol III-associated regulator of small non-coding RNAs that is linked with disease-associated protein agregation. Molecular Cell.
    • Stroo E, Koopman M, Nollen EAA, Mata-Cabana A. (2017) Cellular Regulation of Amyloid Formation in Aging and Disease. Frontiers in Neuroscience.  
    • Perni M , Galvagnion C, Maltsev A, Meisl G, Müller MB, Challa PK, Kirkegaard JB, Flagmeier P, Cohen SI, Cascella R, Chen SW, Limboker R, Sormanni P, Heller GT, Aprile FA, Cremades N, Cecchi C, Chiti F, Nollen EA, Knowles TP, Vendruscolo M, Bax A, Zasloff M, Dobson CM.(2017) A natural product inhibits the initiation of α-synuclein aggregation and suppresses its toxicity. PNAS.
    • Jansen IE, Ye H, Heetveld S, Lechler MC, Michels H, Seinstra RI, Lubbe SJ, Drouet V, Lesage S, Majounie E, Gibbs JR, Nalls MA, Ryten M, Botia JA, Vandrovcova J, Simon-Sanchez J, Castillo-Lizardo M, Rizzu P, Blauwendraat C, Chouhan AK, Li Y, Yogi P, Amin N, van Duijn CM; International Parkinson’s Disease Genetics Consortium (IPGDC), Morris HR, Brice A, Singleton AB, David DC, Nollen EA, Jain S, Shulman JM, Heutink P. (2017) Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing. Genome Biology.
    • Michels H, Seinstra RI , Uitdehaag JC , Koopman M, van Faassen M, Martineau CN, Kema IP, Buijsman R, Nollen EA. (2016) Identification of an evolutionary conserved structural loop that is required for the enzymatic and biological function of tryptophan 2,3-dioxygenase. Scientific Reports.
    • Koopman M , Michels H , Dancy BM, Kamble R, Mouchiroud L, Auwerx J, Nollen EA, Houtkooper RH. (2016) A screening-based platform for the assessment of cellular respiration in Caenorhabditis elegans. Nature Protocols.
    • Visscher M, De Henau S, Wildschut MH, van Es RM, Dhondt I, Michels H, Kemmeren P, Nollen EA, Braeckman BP, Burgering BM, Vos HR, Dansen TB. (2016) Proteome-wide Changes in Protein Turnover Rates in C. elegans Models of Longevity and Age-Related Disease. Cell Reports.
    • Habchi J, Arosio P, Perni M, Costa AR, Yagi-Utsumi M, Joshi P, Chia S, Cohen SI, Müller MB, Linse S, Nollen EA, Dobson CM, Knowles TP, Vendruscolo M. (2016) An anticancer drug suppresses the primary nucleation reaction that initiates the production of the toxic Aβ42 aggregates linked with Alzheimer's disease. Science Advances.  
    • Srinivasan B, Baratashvili M, van der Zwaag M, Kanon B, Colombelli C, Lambrechts RA, Schaap O, Nollen EA, Podgoršek A, Kosec G, Petković H, Hayflick S, Tiranti V, Reijngoud DJ, Grzeschik NA, Sibon OC. (2015) Extracellular 4'-phosphopantetheine is a source for intracellular coenzyme A synthesis. Nature Chemical Biology.  
    • Sin O, Nollen EA.(2015) Regulation of protein homeostasis in neurodegenerative diseases: the role of coding and non-coding genes. Cellular and Molecular Life Sciences.
    • Sin O, Michels H, Nollen EA. (2014) Genetic screens in Caenorhabditis elegans models for neurodegenerative diseases. Biochim Biophys Acta.
    • van der Goot AT, Nollen EA. (2013) Tryptophan metabolism: entering the field of aging and age-related pathologies. Trends in Molecular Medicine.
    • Holmberg M, Nollen EA. Analyzing modifiers of protein aggregation in C. elegans by native agarose gel electrophoresis.(2013) Methods Molecular Biology.
    • van der Goot AT, Nollen EA. (2013) Tryptophan metabolism: entering the field of aging and age-related pathologies. Trends Molecular Medicine.
    • van der Goot AT, Zhu W, Vázquez-Manrique RP, Seinstra RI, Dettmer K, Michels H, Farina F, Krijnen J, Melki R, Buijsman RC, Ruiz Silva M, Thijssen KL, Kema IP, Neri C, Oefner PJ, Nollen EA. (2012) Delaying aging and the aging-associated decline in protein homeostasis by inhibition of tryptophan degradation. PNAS.
    • Falsone SF, Meyer NH, Schrank E, Leitinger G, Pham CL, Fodero-Tavoletti MT, Holmberg M, Dulle M, Scicluna B, Gesslbauer B, Rückert HM, Wagner GE, Merle DA, Nollen EA, Kungl AJ, Hill AF, Cappai R, Zangger K. (2012) SERF protein is a direct modifier of amyloid fiber assembly. Cell Reports.
    • Siudeja K, Srinivasan B, Xu L, Rana A, de Jong J, Nollen EA, Jackowski S, Sanford L, Hayflick S, Sibon OC. (2011) Impaired Coenzyme A metabolism affects histone and tubulin acetylation in Drosophila and human cell models of pantothenate kinase associated neurodegeneration. EMBO Molecular Medicine.
    • Teuling E, Bourgonje A, Veenje S, Thijssen K, de Boer J, van der Velde J, Swertz M, Nollen E. (2011) Modifiers of mutant huntingtin aggregation: functional conservation of C. elegans-modifiers of polyglutamine aggregation. PLoS Currents.
    • Kaminski Schierle GS, Bertoncini CW, Chan FT, van der Goot AT, Schwedler S, Skepper J, Schlachter S, van Ham T, Esposito A, Kumita JR, Nollen EA, Dobson CM, Kaminski CF. (2011) A FRET sensor for non-invasive imaging of amyloid formation in vivo. Chemphyschem.
    • van Ham TJ, Holmberg MA, van der Goot AT, Teuling E, Garcia-Arencibia M, Kim HE, Du D, Thijssen KL, Wiersma M, Burggraaff R, van Bergeijk P, van Rheenen J, Jerre van Veluw G, Hofstra RM, Rubinsztein DC, Nollen EA. (2010) Identification of MOAG-4/SERF as a regulator of age-related proteotoxicity. Cell.
    • van Ham TJ, Breitling R, Swertz MA, Nollen EA. (2009) Neurodegenerative diseases: Lessons from genome-wide screens in small model organisms. EMBO Molecular Medicine.
    • van Ham TJ, Esposito A, Kumita JR, Hsu ST, Kaminski Schierle GS, Kaminski CF, Dobson CM, Nollen EA, Bertoncini CW. (2009) Towards multiparametric fluorescent imaging of amyloid formation: studies of a YFP model of alpha-synuclein aggregation. Journal of Molecular Biology.
    • Roodveldt C, Bertoncini CW, Andersson A, van der Goot AT, Hsu ST, Fernández-Montesinos R, de Jong J, van Ham TJ, Nollen EA, Pozo D, Christodoulou J, Dobson CM.. (2009) Chaperone proteostasis in Parkinson's disease: stabilization of the Hsp70/alpha-synuclein complex by Hip. The EMBO Journal.
    • van Ham TJ, Thijssen KL, Breitling R, Hofstra RM, Plasterk RH, Nollen EA. (2008) C. elegans model identifies genetic modifiers of alpha-synuclein inclusion formation during aging. PLoS Genetics.
    • van Haaften G, Vastenhouw NL, Nollen EA, Plasterk RH, Tijsterman M. (2004) Gene interactions in the DNA damage-response pathway identified by genome-wide RNA-interference analysis of synthetic lethality. PNAS.
    • Nollen EA, Garcia SM, van Haaften G, Kim S, Chavez A, Morimoto RI, Plasterk RH. (2004) Genome-wide RNA interference screen identifies previously undescribed regulators of polyglutamine aggregation. PNAS.
    • Kim S, Nollen EA, Kitagawa K, Bindokas VP, Morimoto RI. (2002) Polyglutamine protein aggregates are dynamic. Nature Cell Biology.
    • Nollen EA, Morimoto RI. (2002) Chaperoning signaling pathways: molecular chaperones as stress-sensing 'heat shock' proteins. Journal of cell science.
    • Nollen EA, Salomons FA, Brunsting JF, van der Want JJ, Sibon OC, Kampinga HH. (2001) Dynamic changes in the localization of thermally unfolded nuclear proteins associated with chaperone-dependent protection. PNAS.
    • Nollen EA, Kabakov AE, Brunsting JF, Kanon B, Höhfeld J, Kampinga HH. (2000) Modulation of in vivo HSP70 chaperone activity by Hip and Bag-1. The journal of biological chemistry.
    • Nollen EA, Brunsting JF, Song J, Kampinga HH, Morimoto RI. (2000) Bag1 functions in vivo as a negative regulator of Hsp70 chaperone activity. Molecular and cellular biology.
    • Nollen EA, Brunsting JF, Roelofsen H, Weber LA, Kampinga HH. (1999) In vivo chaperone activity of heat shock protein 70 and thermotolerance. Molecular and cellular biology.
    • van der Leij FR, Roelofsen H, Niezen-Koning KE, Nollen EA, Kuipers JR. (1999) Confocal laser scanning microscopy of human skin fibroblasts showing transient expression of a green fluorescent carnitine palmitoyltransferase 1 fusion protein. Advances in experimental medicine and biology.
    • Martens DE, Nollen EA, Hardeveld M, van der Velden-de Groot CA, de Gooijer CD, Beuvery EC, Tramper J. (1996) Death rate in a small air-lift loop reactor of vero cells grown on solid microcarriers and in macroporous microcarriers. Cytotechnology.
    • Peters SA, Verver J, Nollen EA, van Lent JW, Wellink J, van Kammen A. (1994) The NTP-binding motif in cowpea mosaic virus B polyprotein is essential for viral replication. The journal of general virology.
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