Honors & Awards

  • Maximum Distinction, Universidad de Chile (2013)
  • Fondecyt (ANID) International Graduate Scholarship, Chilean Government (2014)
  • Pew Latin American Fellow, Postdoctoral Fellowship, The Pew Trusts (2020)

Professional Education

  • Bachelor of Science, Universidad de Chile, Molecular Biotechnology (2013)
  • Professional Title, Universidad de Chile, Molecular Biotechnology (Professional Engineer) (2014)
  • Doctor of Philosophy, The University of Manchester, Biotechnology, Bioscience Enterprise and Molecular Biology (2018)

Stanford Advisors

All Publications

  • A hierarchical assembly pathway directs the unique subunit arrangement of TRiC/CCT. Molecular cell Betancourt Moreira, K., Collier, M. P., Leitner, A., Li, K. H., Lachapel, I. L., McCarthy, F., Opoku-Nsiah, K. A., Morales-Polanco, F., Barbosa, N., Gestaut, D., Samant, R. S., Roh, S., Frydman, J. 2023


    How the essential eukaryotic chaperonin TRiC/CCT assembles from eight distinct subunits into a unique double-ring architecture remains undefined. We show TRiC assembly involves a hierarchical pathway that segregates subunits with distinct functional properties until holocomplex (HC) completion. A stable, likely early intermediate arises from small oligomers containing CCT2, CCT4, CCT5, and CCT7, contiguous subunits that constitute the negatively charged hemisphere of the TRiC chamber, which has weak affinity for unfolded actin. The remaining subunits CCT8, CCT1, CCT3, and CCT6, which comprise the positively charged chamber hemisphere that binds unfolded actin more strongly, join the ring individually. Unincorporated late-assembling subunits are highly labile in cells, which prevents their accumulation and premature substrate binding. Recapitulation of assembly in a recombinant system demonstrates that the subunits in each hemisphere readily form stable, noncanonical TRiC-like HCs with aberrant functional properties. Thus, regulation of TRiC assembly along a biochemical axis disfavors the formation of stable alternative chaperonin complexes.

    View details for DOI 10.1016/j.molcel.2023.07.031

    View details for PubMedID 37625406

  • Nuclear and cytoplasmic spatial protein quality control is coordinated by nuclear-vacuolar junctions and perinuclear ESCRT. Nature cell biology Sontag, E. M., Morales-Polanco, F., Chen, J. H., McDermott, G., Dolan, P. T., Gestaut, D., Le Gros, M. A., Larabell, C., Frydman, J. 2023


    Effective protein quality control (PQC), essential for cellular health, relies on spatial sequestration of misfolded proteins into defined inclusions. Here we reveal the coordination of nuclear and cytoplasmic spatial PQC. Cytoplasmic misfolded proteins concentrate in a cytoplasmic juxtanuclear quality control compartment, while nuclear misfolded proteins sequester into an intranuclear quality control compartment (INQ). Particle tracking reveals that INQ and the juxtanuclear quality control compartment converge to face each other across the nuclear envelope at a site proximal to the nuclear-vacuolar junction marked by perinuclear ESCRT-II/III protein Chm7. Strikingly, convergence at nuclear-vacuolar junction contacts facilitates VPS4-dependent vacuolar clearance of misfolded cytoplasmic and nuclear proteins, the latter entailing extrusion of nuclear INQ into the vacuole. Finding that nuclear-vacuolar contact sites are cellular hubs of spatial PQC to facilitate vacuolar clearance of nuclear and cytoplasmic inclusions highlights the role of cellular architecture in proteostasis maintenance.

    View details for DOI 10.1038/s41556-023-01128-6

    View details for PubMedID 37081164

    View details for PubMedCentralID 6671943

  • Cotranslational Mechanisms of Protein Biogenesis and Complex Assembly in Eukaryotes Annual Reviews of Biomedical Data Science Morales-Polanco, F., Lee, J. H., Barbosa, N. M., Frydman, J. 2022; 5
  • Ageing exacerbates ribosome pausing to disrupt cotranslational proteostasis Nature Stein, K. C., Morales-Polanco, F., Leinden, J. v., Rainbolt, K. T., Frydman, J. 2022
  • A Comprehensive Enumeration of the Human Proteostasis Network. 1. Components of Translation, Protein Folding, and Organelle-Specific Systems Biorxiv Consortium, T. P., 2022
  • An ESCRT-dependent pathway of Nuclear and Cytoplasmic Spatial PQC is coordinated at Nuclear Vacuolar Junctions Biorxiv Sontag, E. M., Morales-Polanco, F., Chen, J., McDermott, G., Dolan, P. T., Gestaut, D., Le Gros, M. A., Larabell, C., Frydman, J. 2022
  • Core Fermentation (CoFe) granules focus coordinated glycolytic mRNA localization and translation to fuel glucose fermentation. iScience Morales-Polanco, F. n., Bates, C. n., Lui, J. n., Casson, J. n., Solari, C. A., Pizzinga, M. n., Forte, G. n., Griffin, C. n., Garner, K. E., Burt, H. E., Dixon, H. L., Hubbard, S. n., Portela, P. n., Ashe, M. P. 2021; 24 (2): 102069


    Glycolysis is a fundamental metabolic pathway for glucose catabolism across biology, and glycolytic enzymes are among the most abundant proteins in cells. Their expression at such levels provides a particular challenge. Here we demonstrate that the glycolytic mRNAs are localized to granules in yeast and human cells. Detailed live cell and smFISH studies in yeast show that the mRNAs are actively translated in granules, and this translation appears critical for the localization. Furthermore, this arrangement is likely to facilitate the higher level organization and control of the glycolytic pathway. Indeed, the degree of fermentation required by cells is intrinsically connected to the extent of mRNA localization to granules. On this basis, we term these granules, core fermentation (CoFe) granules; they appear to represent translation factories, allowing high-level coordinated enzyme synthesis for a critical metabolic pathway.

    View details for DOI 10.1016/j.isci.2021.102069

    View details for PubMedID 33554071

    View details for PubMedCentralID PMC7859310

  • Glycolytic mRNAs localise and are translated in Core Fermentation (CoFe) granules to fuel glucose fermentation BioRxiv Morales Polanco, F., Bates, C., Lui, J., Solari, C., Ashe, M., et al 2020

    View details for DOI 10.1101/741231

  • Translation factor mRNA granules direct protein synthetic capacity to regions of polarized growth. The Journal of cell biology Pizzinga, M., Bates, C., Lui, J., Forte, G., Morales-Polanco, F., Linney, E., Knotkova, B., Wilson, B., Solari, C. A., Berchowitz, L. E., Portela, P., Ashe, M. P. 2019


    mRNA localization serves key functions in localized protein production, making it critical that the translation machinery itself is present at these locations. Here we show that translation factor mRNAs are localized to distinct granules within yeast cells. In contrast to many messenger RNP granules, such as processing bodies and stress granules, which contain translationally repressed mRNAs, these granules harbor translated mRNAs under active growth conditions. The granules require Pab1p for their integrity and are inherited by developing daughter cells in a She2p/She3p-dependent manner. These results point to a model where roughly half the mRNA for certain translation factors is specifically directed in granules or translation factories toward the tip of the developing daughter cell, where protein synthesis is most heavily required, which has particular implications for filamentous forms of growth. Such a feedforward mechanism would ensure adequate provision of the translation machinery where it is to be needed most over the coming growth cycle.

    View details for DOI 10.1083/jcb.201704019

    View details for PubMedID 30877141