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.

Group Info

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.

Senior Postdoctoral Fellows

Celine Martineau

Celine Martineau

PhD Students

Esther Stroo

Esther Stroo

Publications

Siudeja K, Srinivasan B, Xu L, Rana A, de Jong J, Nollen EA, Jackowski S, Sanford L, Hayflick S, Sibon OC. (2012) Impaired Coenzyme A metabolism affects histone and tubulin acetylation in Drosophila and human cell models of pantothenate kinase associated neurodegeneration. EMBO 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.

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, Esposito A, Kumita JR, Hsu ST, Kaminski Schierle GS, Kaminski CF, Dobson CM, Nollen EA, Bertoncini CW. (2010) 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, Breitling R, Swertz MA, Nollen EA. (2009) Neurodegenerative diseases: Lessons from genome-wide screens in small model organisms. EMBO Molecular Medicine.

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. (2001) 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.