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SUMMARY:Quantitative approaches of live single-cell transcriptomics - Prof
 essor Nancy Papalopulu (School of Medical Sciences\, University of Manches
 ter) &amp\; Professor Jonathan Chubb (MRC LMCB\, University College London
 )
DTSTART:20200311T180000Z
DTEND:20200311T200000Z
UID:TALK140275@talks.cam.ac.uk
CONTACT:Dr. Adrien Hallou
DESCRIPTION:Transcriptional dynamics and cellular decision making - Profes
 sor Nancy Papalopulu  \n\nIn recent years\, our understanding of how cells
  make cell state transitions has been transformed by discovery of short-ti
 me scale protein expression oscillatory dynamics. Ultradian oscillations a
 re exemplified by the expression of HES/Her transcription factors in neura
 l progenitors\, but it is not known whether oscillations occur in vivo and
  what is the role of noise. This talk will describe a quantitative and dyn
 amic single cell live imaging approach to analyse ultradian oscillations a
 nd noise during cell state transitions during mouse and zebrafish neural d
 evelopment. With a combination of mathematical modeling and experimentatio
 n we report that in mouse ex-vivo slices Hes5 protein expression noise has
  an oscillatory “priming” function\, where stochastic conversions betw
 een dynamics are enabled\, correlating with a transition to differentiatio
 n. However\, CRISPR/Cas9 mutagenesis of a miR-9 binding site in a knock-in
  Her6 reporter in zebrafish shows that increased high frequency noise has 
 the opposite effect in that it interferes with oscillations and at the sam
 e time locks cells in a progenitor state. These findings show that a trans
 ient oscillatory state appears during cell state transitions and that nois
 e optimization at this stage is necessary for decoding to occur.\n\nTransc
 riptional dynamics and cellular decision making - Professor Jonathan Chubb
 \n\nTo allow a deeper understanding of cell decision making\, and the gene
 ration of more useful conceptual frameworks\, we have developed and implem
 ented a range of technologies- with the view that to understand the decisi
 on of cell requires monitoring a broad range of regulatory features of sin
 gle cells\, as they differentiate.  These approaches encompass both imagi
 ng and transcriptomic methods for monitoring the signalling and gene expre
 ssion dynamics of single cells. In particular\, we use imaging to directly
  observe the bursts of activity of individual genes in living cells (see m
 ovie below). This approach provides a real time readout of the gene expres
 sion decisions of the cell\, in parallel with other features of the cells 
 and their environment.   We combine these techniques with detailed quanti
 tative analysis of the data\, and use modelling and molecular genetics to 
 refine our hypotheses. \n
LOCATION:Old Divinity School\, St John's College\, Cambridge CB2 1TP\, UK
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