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

Informations projet

STARTlight

N° de convention de subvention: 798488

DOI

10.3030/798488

Projet clôturé

Date de signature de la CE 19 Mars 2018

Date de début 1 Avril 2018

Date de fin 31 Mars 2020

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 165 598,80

Contribution de l’UE

€ 165 598,80

Coordonné par

RIJKSUNIVERSITEIT GRONINGEN
Netherlands

Periodic Reporting for period 1 - STARTlight (STARTlight: cell cycle START decision unraveled by single-cell microscopy, modeling and optogenetics)

Période du rapport: 2018-04-01 au 2020-03-31

Résumé du contexte et des objectifs généraux du projet

Cells across all kingdoms of life need to maintain tight control on their division process, which they use to replicate themselves. In particular, the decision of cells to initiate a round of division is a ubiquitous and essential process, whose dysregulation can dramatically affect cell viability in simple unicellular organisms, while contributing to carcinogenesis in organisms such as humans. The central goal of this proposal was to determine the key molecular mechanisms behind this decision process. To achieve this, we used a combination of cutting-edge experimental methods with data analysis and mathematical modeling to understand how and when individual budding yeast cells decide to divide. Our results have generated new fundamental knowledge on the regulation of the yeast cell division cycle which, thanks to the high degree of evolutionary conservation of cell division mechanisms among different organisms, may also be applicable to organisms such as humans.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

Our work focused on budding yeast (also known as baker’s yeast), a well-studied and commonly used model organism. Using microscopy and cultivation techniques which enabled us to follow single yeast cells growing under the microscope, we obtained a wealth of new information on the dynamics of cell growth and key proteins that regulate the decision of yeast cells to divide (a process known as START). Our experimental observations were used to build and calibrate a mathematical model of START. This model was tested extensively by comparing its predictions with observed single-cell behaviors under normal and perturbed growth conditions. With our model, we were thus able to elucidate the sequence of molecular events leading up to the decision of cells to enter a new division cycle.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

With our combination of experimental techniques and data analysis procedures, we were able to observe for the first time the dynamics of key START regulators, which had so far remained elusive. This new knowledge enabled us to considerably improve the mathematical modeling of START, which had so far been hampered by the lack of accurate single-cell dynamic data. Our results will be of great interest to biologists studying the regulation of cell division and the development of cancer in human cells.

Mathematical modeling of START incorporating experimental information on key regulator proteins