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SUMMARY:EPFL BioE Talks SERIES  "Mutation Dynamics and Fitness Effects at 
 the Single Cell Level"
DTSTART:20210607T160000
DTEND:20210607T170000
DTSTAMP:20260509T131601Z
UID:d28c800d095d66084e4e988fabd438f2a75c1195f71a879589908281
CATEGORIES:Conferences - Seminars
DESCRIPTION:Prof. Lydia Robert\, Laboratoire Jean Perrin\, CNRS - Sorbonne
  Université\, Paris (F)\nWEEKLY EPFL BIOE TALKS SERIES\n\nAbstract:\nMuta
 tions are the source of genetic variation upon which natural selection act
 s and therefore the driving force of evolution. In order to understand the
  generation of diversity among life forms\, from the variety of Galapagos 
 finches to the spread of antibiotic resistant bacterial strains\, as well 
 as the diversity between cells in an organism\, such as in cancer evolutio
 n\, we need a quantitative characterization of the dynamics of mutation ac
 cumulation as well as their effects on fitness. Although commonly divided\
 , according to their fitness effects\, into three categories\, good\, bad 
 and neutral\, in reality mutations show a distribution of fitness effects 
 (DFE)\, from strongly deleterious to highly beneficial. This distribution 
 is an important quantity in evolutionary biology but is difficult to measu
 re experimentally. In previous studies on microorganisms\, the quality of 
 DFE estimation was often limited by a small sample of mutations and by a s
 ampling bias due to the effect of natural selection\, which purges strongl
 y deleterious mutations. In addition\, the dynamics of the mutation accumu
 lation process has never been experimentally revealed\, due to the lack of
  appropriate tools.\n\nUsing a microfluidic setup we followed the growth o
 f thousands of individual Escherichia coli cells for hundreds of generatio
 ns as they accumulate mutations [1\,2]. Individual cells grow in separate 
 microchannels whose geometry allows blocking natural selection\, thus prod
 ucing an unbiased sample of tens of thousands of mutations. Lethal and str
 ongly deleterious mutations can also be detected as they appear\, in contr
 ast to previous studies. This high-throughput data allowed a quantitative 
 characterization of the DFE\, showing that it is dominated by neutral muta
 tions\, with a surprisingly weak average cost for non-lethal mutations\, a
 nd 1% of lethal mutations. Using a fluorescent reporter of nascent mutatio
 ns based on the expression of fluorescent Mismatch Repair protein MutL\, a
 llowing detecting nascent mutations as fluorescent foci in the cells\, we 
 also follow directly the dynamics of the mutation accumulation process in 
 single cells.\n\nReferences\n1. Robert L.\, Ollion J.\,Robert J.\, Song X.
 \, Matic I.\, Elez M.\, 2018 Science 359(6381):1283-1286\n2. Robert L.\, O
 llion J.\, Elez M.\, 2019 Nat. Protoc. 14(11):3126-3143\n\n\nBio:\nAfter a
  PhD in microbiology combining experiments and modeling\, Lydia Robert joi
 ned the Jean Perrin Laboratory in 2010. Her research has revolved mainly a
 round three themes\, namely the cell cycle\, stochastic gene expression\, 
 and mutagenesis. She addresses these different questions with a multidisci
 plinary approach\, combining theory (stochastic processes\, statistics) an
 d experiments (microbiology\, genetics\, microfluidics\, microscopy)\, and
  using bacteria as model organisms. In collaboration with Marina Elez\, Ly
 dia Robert recently developed an innovative experimental system to monitor
  mutations appearing in single cells in real time. This system allows inve
 stigating mutagenesis and evolution at the single cell level.\n\n\nZoom li
 nk (with registration) for attending remotely: https://go.epfl.ch/EPFLBioE
 Talks\n\n\nIMPORTANT NOTICE: due to restrictions resulting from the ongoin
 g Covid-19 pandemic\, this seminar can be followed via Zoom web-streaming 
 only\, (following prior one-time registration through the link above).
LOCATION:via Zoom web-streaming only\, due to Covid-19 pandemic https://go
 .epfl.ch/EPFLBioETalks https://go.epfl.ch/EPFLBioETalks
STATUS:CONFIRMED
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