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 Functions 2019
    2017 Kctd13 deletion reduces synaptic transmission via increased RhoA 2017
    2016 CHOPCHOP v2: a web tool for the next generation of CRISPR genome engineering 2016
    2016 Internal guide RNA interactions interfere with Cas9-mediated cleavage 2016
    2016 Polq-Mediated End Joining Is Essential for Surviving DNA Double-Strand Breaks during Early Zebrafish Development 2016
    2014 Massively parallel determination and modeling of endonuclease substrate specificity 2014
    2014 Efficient mutagenesis by Cas9 protein-mediated oligonucleotide insertion and large-scale assessment of single-guide RNAs 2014
    2014 Reprogramming homing endonuclease specificity through computational design and directed evolution 2014
    2014 Progressive engineering of a homing endonuclease genome editing reagent for the murine X-linked immunodeficiency locus 2014
    2012 Improved modeling of side-chain-base interactions and plasticity in protein-dna interface design 2012
    2011 Mining endonuclease cleavage determinants in genomic sequence data 2011
    2011 A synthetic homing endonuclease-based gene drive system in the human malaria mosquito 2011
    2009 Exploitation of binding energy for catalysis and design 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 complex 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
  • Full Name

  • Summer Thyme