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 read-outs.Monitoring of individu...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 read-outs.Monitoring of individual responses to drug treatments would however be more informative.Here,a new strategy to track different phenotypic traits of individual C.elegans nematodes throughout their full life-cycle-i.e.,embryonic and post-embryonic development,until adulthood onset,differently from life-span-is presented.In 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 development.Several phenotypes were monitored and quantified for each animal,resulting in high-content phenome data.Specifically,the method was validated by analyzing the response of C.elegans to doxycycline,an antibiotic fairly well-known to prolong the development and activate mitochondrial stress-response pathways in different species.Interestingly,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 dataset.Such heterogeneous response started during the embryonic development,which makes essential having a dedicated chip that allows including this early developmental stage in the drug assay.Our approach would therefore allow elucidating pharmaceutical or therapeutic responses that so far were still being overlooked.展开更多
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)+4 种基金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).
文摘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 read-outs.Monitoring of individual responses to drug treatments would however be more informative.Here,a new strategy to track different phenotypic traits of individual C.elegans nematodes throughout their full life-cycle-i.e.,embryonic and post-embryonic development,until adulthood onset,differently from life-span-is presented.In 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 development.Several phenotypes were monitored and quantified for each animal,resulting in high-content phenome data.Specifically,the method was validated by analyzing the response of C.elegans to doxycycline,an antibiotic fairly well-known to prolong the development and activate mitochondrial stress-response pathways in different species.Interestingly,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 dataset.Such heterogeneous response started during the embryonic development,which makes essential having a dedicated chip that allows including this early developmental stage in the drug assay.Our approach would therefore allow elucidating pharmaceutical or therapeutic responses that so far were still being overlooked.
