Sackler/PEB Distinguished Speaker

Event time: 
Thursday, November 9, 2017 - 4:00pm
Location: 
Sloane Physics Laboratory, Room 56 See map
217 Prospect St.
New Haven, CT 06511
Event description: 

Prof. Hernan G. Garcia, Department of Physics, UC Berkeley 

location: SPL Room 56

FLYER

How, when and where in pattern formation: Spying on embryonic development one molecule at a time

 

An abiding mystery in biology is how a single cell develops into a multicellular organism. Despite great advances in identifying the molecular players of developmental programs, the quantitative prediction of gene expression patterns from knowledge of DNA regulatory sequence has proven elusive. Technological limitations have kept us in the dark about the dynamics of these regulatory decisions, a necessary first step towards the predictive understanding of developmental response. In this talk I present new technologies and theoretical methods to access and predict developmental decisions in living fruit fly embryos at the single nucleus level. Using this approach we can measure where, when and how fast nuclei express a gene in response to an input morphogen and bridge these dynamics to the resulting macroscopic domains of gene expression that arise throughout the embryo and that lead to the specification of future body parts. In contradiction with the standard picture of gene regulation, we discovered that transcription factors can regulate gene activity in three seemingly decoupled ways. First, they determine a random subset of nuclei that is able to participate in the regulatory game. Second, for those promoters that are randomly turned on, transcription factors also dictate the dynamics with which mRNA is produced in bursts. Finally, transcription factors also regulate the length of time each promoter will partake in gene expression. All of these modes of regulation are necessary in order to create sharp boundaries in the embryo. This work provides a framework to predictively understand and control developmental response by identifying the different regulatory strategies employed by the fly in the generation of patterns of gene expression.