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Martí Aldea: Spatial control of cell cycle entry

Lab Presentation

Protein misfolding and accumulation of proteotoxic aggregates has a direct impact in cell aging, but the underlying molecular mechanisms are poorly understood. Although it has been mainly associated to neurodegenerative diseases, recent evidence has linked proteostasis defects to cell precursor damage in proliferative tissues. As in many cell types of different origin, prion-like aggregates are asymmetrically distributed during cytokinesis in budding yeast, and we have found that their progressive accumulation through consecutive generations eventually inhibits cell cycle entry and leads the cell to an irreversible senescent state. Since prion-like and proteotoxic aggregates act as chaperone sinks, our data point to the idea that chaperome alterations would mediate the observed decline in cell proliferation during cell aging. With these hypothesis we aim at the identification of key molecules and mechanisms that restrain cell proliferation during cell aging and, hence, at a better understanding of aging at a systems level.

Martí Aldea Malo

Principal Investigator



Past students

Most relevant publications

  • Georgieva MV, Yahya G, Codó L, Ortiz R, Teixidó L, Claros J, Jara R, Jara M, Iborra A, Gelpí JL, Gallego C, Orozco M, Aldea M. Inntags: small self-structured epitopes for innocuous protein tagging. Nature Methods doi:10.1038/nmeth.3556 (2015) 
     
  • Yahya G, Parisi E, Flores A, Gallego C, Aldea M. A Whi7-anchored loop controls the G1 Cdk-cyclin complex at Start. Molecular Cell 53, 115-126 (2014) 
     
  • Menoyo S, Ricco N, Bru S, Hernández-Ortega S, Escoté X, Aldea M, Clotet J. Phosphate-activated cyclin-dependent kinase stabilizes G1 cyclin to trigger cell cycle entry. Molecular and Cellular Biology 33, 1273-1284 (2013) 
     
  • Ferrezuelo F, Colomina N, Palmisano A, Garí E, Gallego C, Csikász-Nagy A, Aldea M. The critical size is set at a single-cell level by growth rate to attain homeostasis and adaptation. Nature Communications 3, 1012 (2012)
     
  • Ruiz-Miró, M; Colomina, N; Fernández, RM; Garí, E; Gallego, C; Aldea, M. Translokin interacts with cyclin D1 and prevents its nuclear accumulation in quiescent cells. Traffic 12, 549-562 (2011)
     
  • Ferrezuelo, F; Colomina, N; Futcher, B; Aldea, M. The transcriptional network activated by Cln3 cyclin at the G1-to-S transition of the yeast cell cycle. Genome Biology 11, R67 (2010)
     
  • Cambray, S; Pedraza, N; Rafel, M; Garí, E; Aldea, M; Gallego, C. Protein kinase KIS localizes to RNA granules and enhances local translation.Molecular and Cellular Biology 29, 726-735 (2009)
     
  • Vergés, E; Colomina, N; Garí, E; Gallego, C; Aldea, M. Cyclin Cln3 is retained at the ER and released by the J-chaperone Ydj1 in late G1. Molecular Cell 26, 649-662 (2007)
     
  • Aldea, M; Colomina, N; Garí, E. Control of cell cycle and cell growth by molecular chaperones. Cell Cycle 6, 1-4 (2007, review)
     
  • Clotet, J; Escoté, X; Adrover, MA; Garí, E; Aldea, M; De Nadal, E; Posas, F. Multiple checkpoint activation by the Hog1 MAPK is required for cell survival upon osmostress. The EMBO Journal 25, 2338-2346 (2006) 
     
  • Liu, Y; Encinas, M; Comella, JX; Aldea, M; Gallego, C. bHLH proteins bind to TrkB and p21Cip1 promoters linking differentiation and cell cycle arrest in neuroblastoma cells. Molecular and Cellular Biology 24, 2662-2672 (2004)
     
  • Wang, H; Garí, E; Vergés, E; Gallego, C; Aldea, M. Recruitment of Cdc28 by Whi3 restricts nuclear accumulation of the G1 cyclin-Cdk complex to late G1. The EMBO Journal 23, 180-191 (2004)
     
  • Colomina, N; Liu, Y; Aldea, M; Garí, E. TOR regulates the subcellular localization of Ime1, a transcriptional activator of meiotic development. Molecular and Cellular Biology 23, 7415-7424 (2003)
     
  • Ferrezuelo, F; Steiner, B; Aldea, M; Futcher, B. Biogenesis of yeast telomerase depends on the importin Mtr10. Molecular and Cellular Biology 22, 6046-6055 (2002)
     
  • Garí, E; Volpe, T; Wang, H; Gallego, C; Futcher, B; Aldea, M. Whi3 binds the mRNA of the G1 cyclin CLN3 to modulate cell fate in budding yeastGenes & Development 15, 2803-2808 (2001)
     
  • Colomina N, Garí E, Gallego C, Herrero E, Aldea M. G1 cyclins block the Ime1 pathway to make mitosis and meiosis incompatible in budding yeast.The EMBO Journal 18, 320-329 (1999)
     
  • Gallego C, Garí E, Colomina N, Herrero E, Aldea M. The Cln3 cyclin is downregulated by translational repression and degradation during the G1 arrest caused by nitrogen deprivation in budding yeast. The EMBO Journal 16, 7196-7206 (1997)

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We offer a PhD student position granted by the Spanish Ministry of Science and Innovation.  Applications will be considered ASAP.

Prions and aggregons as inhibitors of Start: a path to cell ageing

  • Plan Estatal de Investigación Científica y Técnica y de Innovación 2013
  • Ministerio de Innovación y Economía 2014 - 2016
  • PI: Martí Aldea
     

Molecular competition and cell size control

  • Plan Nacional I+D+I 2010
  • Ministerio de Ciencia e Innovación 2011 - 2013
  • PI: Martí Aldea
     

Genomic instability

  • CONSOLIDER-INGENIO 2010
  • Ministerio de Ciencia e Innovación 2008 - 2012
  • PI: Martí Aldea
     

Inntag

  • INNPACTO 2010
  • Ministerio de Ciencia e Innovación 2011 - 2013
  • PI: Martí Aldea

BudJ - ImageJ plugin written by Marti Aldea to analyze cell size and fluorescent parameters of budding yeast (Saccharomyces cerevisiae)   

BudJ image - Sample stack

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