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Seminar

Wednesday, June 20th, 2018
From 11h30 To 12h30
Centre de Recherche - Paris - Amphithéâtre Marie Curie

Clonal dynamics: experimental evolution, clonal hematopoiesis and cancer risk

The dynamics of genetic diversity in large clonally-evolving cell populations are poorly understood, despite having implications for the detection and treatment of cancers. I will describe work where we combine barcode lineage tracking, sequencing of adaptive clones, and mathematical modelling of mutational dynamics to understand how genetic diversity changes in an experimental system. We find that, despite differences in beneficial mutational mechanisms and fitness effects between environments, early adaptive genetic diversity increases predictably, driven by the expansion of many single-mutant lineages.

However, a crash in diversity follows, caused by highly-fit double-mutants fed from exponentially growing single-mutants, a process closely related to the classic Luria-Delbruck experiment. The diversity crash is likely to be a general feature of clonal evolution, however its timing and magnitude is stochastic. I will go onto describe more recent work applying some of these insights to quantitatively understand the clonal evolution that drives clonal hematopoiesis and their implications for predicting subsequent hematologic cancers.

Speaker(s)

Jamie Blundell

Department of Oncology at CRUK Cambridge Center

Invited by

Leila Perié
Director of research

Contact

Leila Perié

Director of research

Send an e-mail

Learn more

Recent publications:

A scalable double-barcode sequencing platform for characterization of dynamic protein-protein interactions
(no URL provided)
Nature Communications  Crossref
25 May 2017 

Development of a Comprehensive Genotype-to-Fitness Map of Adaptation-Driving Mutations in Yeast 
(no URL provided)
Cell   Crossref
01 Sep 

Obstruction of adaptation in diploids by recessive, strongly deleterious alleles
(no URL provided)
Proceedings of the National Academy of Sciences 
Crossref 
19 May 2015 

Quantitative evolutionary dynamics using high-resolution lineage tracking 
(no URL provided)
Nature   Crossref
25 Feb 2015 

Beyond genome sequencing: Lineage tracking with barcodes to study the dynamics of evolution, infection, and cancer (no URL provided)
Genomics   Crossref
01 Dec 2014