Investigating the consequences of asymmetric endoplasmic reticulum inheritance in Saccharomyces cerevisiae under stress using a combination of single cell measurements and mathematical modelling

查看全文 作　　者：Felix [1,2]R.H.Jonas;Kate [2,3]E.Royle;Rochelle [2,3]Aw;Guy-Bart [1,2]V.Stan;Karen [2,3]M.Polizzi 机构地区：[1]Department of Bioengineering,Imperial College London,London,SW72AZ,United Kingdom;[2]Imperial College Centre for Synthetic Biology,London,SW72AZ,United Kingdom;[3]Department of Life Sciences,Imperial College London,London,SW72AZ,United Kingdom 出　　处：《Synthetic and Systems Biotechnology》索引2018年第3卷第1期,共12页 摘　　要：Adaptation allows organisms to maintain a constant internal environment,which is optimised for growth.The unfolded protein response(UPR)is an example of a feedback loop that maintains endoplasmic reticulum(ER)homeostasis,and is characteristic of how adaptation is often mediated by transcriptional networks.The more recent discovery of asymmetric division in maintaining ER homeostasis,however,is an example of how alternative non-transcriptional pathways can exist,but are overlooked by gold standard transcriptomic or proteomic population-based assays.In this study,we have used a combination of fluorescent reporters,flow cytometry and mathematical modelling to explore the relative roles of asymmetric cell division and the UPR in maintaining ER homeostasis.Under low ER stress,asymmetric division leaves daughter cells with an ER deficiency,necessitating activation of the UPR and prolonged cell cycle during which they can recover ER functionality before growth.Mathematical analysis of and simulation results from our mathematical model reinforce the experimental observations that low ER stress primarily impacts the growth rate of the daughter cells.These results demonstrate the interplay between homeostatic pathways and the importance of exploring sub-population dynamics to understand population adaptation to quantitatively different stresses. 关 键 词：ADAPTATION Asymmetric cell division Endoplasmic reticulum stress Unfolded protein response Saccharomyces cerevisiae