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SUMMARY: Decoding Transcriptional Regulation and Kinetics Using Single-Cel
 l Transcriptomics. - Professor Rickard Sandberg\, Karolinska Institutet\, 
 Stockholm\, Sweden
DTSTART:20200206T130000Z
DTEND:20200206T140000Z
UID:TALK129508@talks.cam.ac.uk
CONTACT:Caroline Newnham
DESCRIPTION:The advancement of single-cell RNA-sequencing (scRNA-seq) has 
 opened up for transcriptome-wide analyses of transcriptional regulation an
 d dynamics. My lab developed full-length scRNA-seq protocols (e.g. Smart-s
 eq2 and Smart-seq3) that we use to study patterns of gene expression and r
 egulation at single cell resolution. We recently inferred transcriptional 
 burst kinetics for thousands of endogenous genes using allele-resolved scR
 NA-seq\, which revealed that core promoter elements and enhancers control 
 burst size and frequency\, respectively3. We have inferred allelic waiting
  times between consecutive bursts based on mRNA degradation rates that we 
 are now comparing to direct readouts from 4sU-based labelling of newly tra
 nscribed RNAs in single cells4. Having transcriptome-wide readouts of burs
 ting kinetics enables more detailed investigations into patterns of transc
 riptional dynamics in response to the perturbation of transcriptional regu
 lators and co-factors\, which we are actively pursuing. Moreover\, we are 
 exploring how human genetic variation affects bursting kinetics to be able
  to distinguish the contributions of specific DNA-binding proteins to eith
 er burst size or frequency mediated regulation. Altogether\, transcriptome
 -wide single-cell measurements of gene expression enable quantitative inve
 stigation of the episodic transcription of our genes and opens up for mech
 anistic inquiries into how genomic sequence elements are read by trans-fac
 tors to control transcriptional burst sizes and frequencies. Moreover\, I 
 will introduce our recent Smart-seq3 method that provides unique abilities
  to count RNAs at both allele and isoform resolution.
LOCATION:Biffen Lecture Theatre\, Department of Genetics\, Downing Site
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