PCV - Programme interdiciplinaire en physique et chimie du vivant

Real-time tracking of yeast aging in a single-cell chemostat – AGINGSTAT

Submission summary

Aging is an intrinsic feature of living organisms which is at least partly genetically determined. Despite considerable efforts to identify the mechanisms that govern the transition to senescence, a precise and quantitative understanding at the cellular level is missing, mainly because it has been technically impossible to monitor biological processes over a long enough period of time. The aim of this project is to build a novel apparatus to track in real-time the fate of a single yeast cell from birth to death using a microfluidics-based time-lapse microscope with extended capabilities. The principle of this device is to do long term imaging (typically 100 generations) in a controlled environment by limiting the growth of the colony using laser disruption of the progeny of a single cell. By tracking the successive divisions of a unique cell in stationary conditions, we will be able to observe and characterize the processes involved in replicative aging and decipher the overall mechanisms that lead to senescence. Specific key questions include : 1) what are the kinetics of appearance and the causality of the essential aging markers ? 2) What is the mechanism that prevents the daughter cells from inheriting the senescence phenotype from their aging mother? 3) What is the link between aging and the regulation of the cell cycle machinery ? Further technical developments may lead to the construction of a high throughput system to screen drugs which affect the longevity process. This research project, which relies on the development of a unique biophysical instrument to dramatically increase the timescale of existing single cell assays, may find a natural extension in the study of other epigenetic processes (e.g. chromatin silencing, prion) whose dynamics are poorly understood.

Project coordination

Gilles CHARVIN (Organisme de recherche)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

Help of the ANR 310,000 euros
Beginning and duration of the scientific project: - 48 Months

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