Wednesday, January 16, 2019 at 2:00pm to 3:00pm
Hancock Foundation Building (AHF), Torrey Webb
3616 Trousdale Parkway, Los Angeles, CA 90089
"Lighting up the central dogma in living embryos to uncover how genomic sequence encodes cell fate decisions”
Abstract: Unraveling the mystery of how a single embryonic cell gives rise to the menagerie of differentiated cell types that build an animal will not only reveal the organizing principles of life, but will yield new insights into disorders of development and cancer. Even though classic genetic screens and functional genomic approaches have uncovered essentially all the transcription factors and enhancers involved in specifying cell identity, we still don’t understand how these molecular players work together to choreograph development. Thanks to a recent suite of innovations in live imaging andcomputational analysis methodsthe time is ripe for the introduction of a new quantitative paradigm in the study of development based on how cell fates are established in living animals as development is actually taking place. Indeed, we can now visualize transcription, translation, and even the binding of a single TF molecule to DNA in living Drosophila embryos. I will discuss the technologies we developed to enable this and what we learned by applying them, focusing on a new protein tag, LlamaTag, which makes it possible to visualize transcription factor concentration dynamics in live embryos. Using LlamaTags we discovered stochastic bursts in the concentration of transcription factors that are correlated with bursts in transcription. We further used LlamaTags to show that the concentration of protein in a given nucleus depends heavily on transcription of that gene in neighboring nuclei and show that this short range inter-nuclear coupling is an important mechanism for coordinating gene expression across many nuclei to delineate straight and sharp boundaries of gene expression.