Project description DEENESFRITPL Gaining insight into ageing from bacterial transcriptional regulation Sigma factors are the main constituents of transcription regulation in bacteria, playing a key role in gene expression regulation in response to environmental changes. They could provide insight into heterogeneity in ageing among individuals, going beyond bacteria and observed in diverse populations including humans. Scientific understanding of the molecular control of ageing via genetic and metabolic pathways does not fully explain this heterogeneity demonstrated by different ageing rates and patterns and even observed with fixed genetics and environment. With the support of the Marie Skłodowska-Curie Actions programme, the ASNet project will combine high-tech experimental techniques with mathematical modelling to elucidate the roles and mechanisms of four sigma factors in ageing processes of individual bacterial cells. Show the project objective Hide the project objective Objective Ageing is controlled at the molecular level via genetic and metabolic pathways. Ageing rates and patterns vary substantially even with fixed genetics and environment. However, molecular mechanisms of ageing generating individual heterogeneity are poorly understood. Stochastic dynamics of gene expression can be a main source of the variation in cellular damage dynamics leading to individual heterogeneity in ageing. The sigma factor regulatory networks constitute the core part of the bacterial gene expression networks and therefore play important role in deciding the fate of bacterial cells. In this project, I focus on exploring the role and interplays of four major sigma factors rpoD, rpoS, rpoH, rpoN in individual E. coli cells. I plan to (1) obtain these sigma factors’ expression dynamics and the demographic fates at individual E. coli cells in microfluidic platforms under fluorescent microscope; (2) process and analyze big image data in an automated manner; (3) develop mathematical models to interpret expression and demographic signals for damage and ageing. I will combine the knowledge and methods from the disciplines of molecular biology, genetics, fluorescent microscopy and microfluidics, machine learning, population and evolutionary dynamics and mathematical modelling to shed light on the link from stochastic expression dynamics in sigma factor regulatory network towards individual variations observed in ageing fates. Fields of science natural sciencesphysical sciencesclassical mechanicsfluid mechanicsmicrofluidicsnatural sciencesbiological sciencesgeneticsnatural sciencesbiological sciencesmicrobiologybacteriologynatural sciencesbiological sciencesevolutionary biologynatural sciencesmathematicsapplied mathematicsmathematical model Programme(s) HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme Topic(s) HORIZON-MSCA-2021-PF-01-01 - MSCA Postdoctoral Fellowships 2021 Call for proposal HORIZON-MSCA-2021-PF-01 See other projects for this call Funding Scheme HORIZON-AG-UN - HORIZON Unit Grant Coordinator FREIE UNIVERSITAET BERLIN Net EU contribution € 189 687,36 Address KAISERSWERTHER STRASSE 16-18 14195 Berlin Germany See on map Region Berlin Berlin Berlin Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost No data
