Microfluidics-enabled phenotyping of a whole population of *** worms over their embryonic and post-embryonic development at single-organism resolution
作者机构:Ecole Polytechnique Fédérale de LausanneLaboratory of MicrosystemsLausanneSwitzerland Ecole Polytechnique Fédérale de LausanneLaboratory of Integrative Systems PhysiologyLausanneSwitzerland
出 版 物:《Microsystems & Nanoengineering》 (微系统与纳米工程(英文))
年 卷 期:2018年第4卷第1期
页 面:345-355页
核心收录:
学科分类:083002[工学-环境工程] 0830[工学-环境科学与工程(可授工学、理学、农学学位)] 08[工学]
基 金:This work in the M.A.G.laboratory was supported by the Ecole Polytechnique Fédérale de Lausanne and the EU Ideas program(ERC-2012-AdG-320404) V.S.was supported by the‘EPFL Fellows’program co-funded by Marie Skłodowska-Curie,Horizon 2020 Grant agreement(665667) M.C.and L.M.were supported by the Gebert Rüf Stiftung(GRS-025/16) .The work in the J.A.laboratory is supported by the EPFL,NIH(R01AG043930) Systems X(SySX.ch 2013/153) Velux Stiftung(1019) the Swiss National Science Foundation(31003A-140780)
摘 要:The organism Caenorhabditis elegans is a performant model system for studying human biological processes and diseases,but until now all phenome data are produced as population-averaged *** of individual responses to drug treatments would however be more ***,a new strategy to track different phenotypic traits of individual *** nematodes throughout their full life-cycle-i.e.,embryonic and post-embryonic development,until adulthood onset,differently from life-span-is *** an automated fashion,single worms were synchronized,isolated,and cultured from egg to adulthood in a microfluidic device,where their identity was preserved during their whole *** phenotypes were monitored and quantified for each animal,resulting in high-content phenome ***,the method was validated by analyzing the response of *** to doxycycline,an antibiotic fairly well-known to prolong the development and activate mitochondrial stress-response pathways in different ***,the obtained extensive single-worm phenome not only confirmed the dramatic doxycycline effect on the worm developmental delay,but more importantly revealed subtle yet severe treatment-dependent phenotypes that are representative of minority subgroups and would have otherwise stayed hidden in an averaged *** heterogeneous response started during the embryonic development,which makes essential having a dedicated chip that allows including this early developmental stage in the drug *** approach would therefore allow elucidating pharmaceutical or therapeutic responses that so far were still being overlooked.