Positions

Overview

  • My long-term research goals are to uncover the molecular basis of complex neurodevelopmental and neuropsychiatric diseases and eventually create therapies. I have a broad background in biochemistry, molecular biology, and neurobiology. To gain a fundamental understanding of protein structure and function and the skills to engineer therapeutics, I joined David Baker’s protein modeling lab for my graduate studies (2006-2012). I fused computational and experimental approaches to redesign biomolecular interactions, mastering a wide range of techniques including enzymology, directed protein evolution, multiple coding languages, and high-throughput computing.

    As a Damon Runyon Postdoctoral Research Fellow and K99 recipient in Dr. Alexander Schier’s lab (2012-2019), I established expertise with zebrafish and laid the groundwork for my proposed research on the pathways regulated by genes associated with psychiatric disorders. Zebrafish is an ideal model vertebrate for large-scale genetic and neurodevelopmental studies, as well as high-throughput drug screens. I generated over a hundred zebrafish mutants for schizophrenia-associated genes and assessed their brain activity, brain structure, and behavior. In preparing for this screen, I optimized the efficiency of Cas9-mediated mutagenesis in zebrafish, uncovered rules for Cas9 gRNA design, and made an unexpected discovery about embryonic DNA repair. From the study of over a hundred mutants, I uncovered shared phenotypes and phenotypes that relate to patient physiology, including altered forebrain development and decreased prepulse inhibition. These findings highlighted the most likely candidates in multi-gene loci and prioritized genes for further study. This screen provided the foundation for my independent lab, as I will now decipher the detailed molecular and developmental functions of the most interesting candidates.
  • Selected Publications

    Academic Article

    Year Title Altmetric
    2019 Phenotypic Landscape of Schizophrenia-Associated Genes Defines Candidates and Their Shared FunctionsCell.  177:478-491.e20. 2019
    2017 Kctd13 deletion reduces synaptic transmission via increased RhoANature.  551:227-231. 2017
    2016 CHOPCHOP v2: a web tool for the next generation of CRISPR genome engineeringNucleic Acids Research.  44:W272-W276. 2016
    2016 Internal guide RNA interactions interfere with Cas9-mediated cleavageNature Communications.  7. 2016
    2016 Polq-Mediated End Joining Is Essential for Surviving DNA Double-Strand Breaks during Early Zebrafish DevelopmentCell Reports.  15:707-714. 2016
    2014 Massively parallel determination and modeling of endonuclease substrate specificityNucleic Acids Research.  42:13839-13852. 2014
    2014 Efficient mutagenesis by Cas9 protein-mediated oligonucleotide insertion and large-scale assessment of single-guide RNAsPLoS ONE.  9. 2014
    2014 Reprogramming homing endonuclease specificity through computational design and directed evolutionNucleic Acids Research.  42:2564-2576. 2014
    2014 Progressive engineering of a homing endonuclease genome editing reagent for the murine X-linked immunodeficiency locusNucleic Acids Research.  42:6463-6475. 2014
    2012 Improved modeling of side-chain-base interactions and plasticity in protein-dna interface designJournal of Molecular Biology.  419:255-274. 2012
    2011 Mining endonuclease cleavage determinants in genomic sequence dataJournal of Biological Chemistry.  286:32617-32627. 2011
    2011 A synthetic homing endonuclease-based gene drive system in the human malaria mosquitoNature.  473:212-215. 2011
    2009 Exploitation of binding energy for catalysis and designNature.  461:1300-1304. 2009
    2007 Mechanistic study of competitive sp3-sp3 and sp 2-sp3 carbon-carbon reductive elimination from a platinum (IV) center and the isolation of a C-C agostic complexJournal of the American Chemical Society.  129:9538-9539. 2007

    Chapter

    Year Title Altmetric
    2016 Computational design of DNA-binding proteins.  265-283. 2016
    2014 Redesigning the specificity of protein-DNA interactions with rosetta.  265-282. 2014

    Education And Training

  • University of Washington, Predoctoral Fellowship
  • Harvard University, Postdoctoral Fellowship
  • Harvard University, Postdoctoral Fellowship
  • Harvard University, Postdoctoral Research 2019
  • Doctor of Philosophy in Biochemistry, University of Washington 2012
  • Bachelor of Science or Mathematics in Biology, Scripps College 2006
  • Bachelor of Science or Mathematics in Chemistry, Scripps College 2006
  • Full Name

  • Summer Thyme