STARTlight | STARTlight: cell cycle START decision unraveled by single-cell microscopy, modeling and optogenetics

Summary
Cells across all kingdoms of life have developed exquisite control mechanisms to achieve and maintain the balance between cell growth and division. The decision to commit to cell division is a ubiquitous and essential process, whose dysregulation can dramatically affect cell viability in simple eukaryotes, while leading to tumorigenesis in mammalian cells. In budding yeast, the short interval in late G1 where commitment to cell division is decided, is known as START. Despite years of research, it is still unclear how the transition through START is triggered, and many mutually conflicting hypotheses have been proposed. Recent developments in microfluidics and single-cell microscopy have opened up new avenues for investigating START at the single-cell level. Moreover, thanks to the rapid development of optogenetic tools in the last few years offers the possibility to apply dynamic single-cell perturbations, with great potential for untangling complex intracellular networks. By combining single-cell time-course data on key components of the START network with targeted, reversible and dynamic perturbation of their activities using optogenetic tools, the aim of this proposal is to unravel the mechanisms that trigger START in budding yeast and to quantitatively describe these processes in a mathematical model. The results of this project will thus provide new fundamental knowledge on cell cycle regulation which, thanks to the high degree of conservation between yeast and higher eukaryotes, will be transferrable to other organisms as well.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/798488
Start date: 01-04-2018
End date: 31-03-2020
Total budget - Public funding: 165 598,80 Euro - 165 598,00 Euro
Cordis data

Original description

Cells across all kingdoms of life have developed exquisite control mechanisms to achieve and maintain the balance between cell growth and division. The decision to commit to cell division is a ubiquitous and essential process, whose dysregulation can dramatically affect cell viability in simple eukaryotes, while leading to tumorigenesis in mammalian cells. In budding yeast, the short interval in late G1 where commitment to cell division is decided, is known as START. Despite years of research, it is still unclear how the transition through START is triggered, and many mutually conflicting hypotheses have been proposed. Recent developments in microfluidics and single-cell microscopy have opened up new avenues for investigating START at the single-cell level. Moreover, thanks to the rapid development of optogenetic tools in the last few years offers the possibility to apply dynamic single-cell perturbations, with great potential for untangling complex intracellular networks. By combining single-cell time-course data on key components of the START network with targeted, reversible and dynamic perturbation of their activities using optogenetic tools, the aim of this proposal is to unravel the mechanisms that trigger START in budding yeast and to quantitatively describe these processes in a mathematical model. The results of this project will thus provide new fundamental knowledge on cell cycle regulation which, thanks to the high degree of conservation between yeast and higher eukaryotes, will be transferrable to other organisms as well.

Status

CLOSED

Call topic

MSCA-IF-2017

Update Date

28-04-2024
Geographical location(s)
Structured mapping
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EU-Programme-Call
Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.3. EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions (MSCA)
H2020-EU.1.3.2. Nurturing excellence by means of cross-border and cross-sector mobility
H2020-MSCA-IF-2017
MSCA-IF-2017