Helge Grosshans
Group News
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Jan 23, 2023 Identified: components of the molecular clock that helps some animals shed their skin |
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Jun 7, 2022 How animals reach their correct size |
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Apr 13, 2021 When two worlds meet: a protease that controls small RNA activity |
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Jul 21, 2020 A developmental clock with a checkpoint function |
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Apr 5, 2020 The circuitous path to adulthood |
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Helge Grosshans
Biological clocks and timers in development
The development of an animal requires proper temporal synchronization of diverse events, facilitated by developmental clocks. How such clocks function is only beginning to emerge. What are their properties? What are the components that make them run, and how are they wired? To solve these questions, we investigate developmental timing in the roundworm C. elegans, where we can exploit our recent discovery that thousands of genes oscillate in expression during larval development. Such extensive and robust molecular clock output, combined with powerful tools for genetic manipulation and screening, makes C. elegans uniquely suited for dissecting the underlying clock mechanism. We combine high-throughput single animal-based methods including quantitative time-lapse imaging with genomics, genetic and computational approaches to record and alter oscillations and developmental timing. Thus, we aim to establish a mechanistic and quantitative model of the clock.
Although oscillator-based developmental clocks are crucial to control execution of repetitive events such as the formation of vertebrae in mammals, distinct mechanisms time linear progression. For instance, transition from juvenile (larval) to adult fates in C. elegans relies on a regulatory cascade, where an RNA-binding protein, LIN28, represses a miRNA, let-7, which in turn represses another RNA-binding protein, LIN41/TRIM71. The functions of these factors appear conserved in mammals where they regulate stem cell fates and, possibly, the onset of puberty. Working with C. elegans and mammalian cells, we aim to obtain a full mechanistic understanding of this pathway and its components to understand how control of 'linear time' is achieved and integrated with clock-controlled processes.
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Helge Grosshans
This is a list of selected publications from this group. For a full list of publications, please visit our Publications page and search by group name.
Meeuse MWM, Hauser YP, Nahar S, Smith AAT, Braun K, Azzi C, Rempfler M, Grosshans H (2023) C. elegans molting requires rhythmic accumulation of the Grainyhead/LSF transcription factor GRH-1
EMBO J. 2023 Jan 23:e111895Gudipati, R.K., Braun, K., Gypas, F., Hess, D., Schreier, J.,Carl, S.H., Ketting, R.F., and Grosshans, H. (2021) Protease-mediated processing of Argonaute proteins controls small RNA association.
Molecular Cell, Volume 81, Issue 11, Pages 2388-2402.e8Tsiairis, C., and Grosshans, H. (2021) Gene expression oscillations in C. elegans underlie a new developmental clock.
Current Topics in Developmental Biology, Volume 144, 2021, Pages 19-43Meeuse, M.W.M.*, Hauser, Y.P.*, Morales Moreno, L.J., Hendriks, G.-J., Eglinger, J., Bogaarts, G., Tsiairis, C., Grosshans, H. (2020) Developmental function and state transitions of a gene expression oscillator in C. elegans
Mol Syst Biol. 16: e9498(* equal contribution)
Azzi, C.*, Aeschimann, F.*, Neagu, A., and Grosshans, H. (2020) A branched heterochronic pathway directs juvenile-to-adult transition through two LIN-29 isoforms
eLIFE 9: e53387(* equal contribution)
Welte, T.*, Tuck, A.C.*, Papasaikas, P., Carl, S.H., Flemr, M., Knuckles, P., Rankova, A., Bühler, M., and Grosshans, H. (2019) The RNA hairpin binder TRIM71 modulates alternative splicing by repressing MBNL1
Genes Dev. 33:1221-1235(* equal contribution)
Brancati, G., and Grosshans, H. (2018) An interplay of miRNA abundance and target site architecture determines miRNA activity and specificity
Nucleic Acids Res. 46: 3259-3269Aeschimann F, Kumari P, Bartake H, Gaidatzis D, Xu L, Ciosk R, Grosshans H (2017) LIN41 post-transcriptionally silences mRNAs by two distinct and position-dependent mechanisms
Mol Cell 65:476-489.de la Mata M, Gaidatzis D, Vitanescu M, Stadler MB, Wentzel C, Scheiffele P, Filipowicz W, Grosshans H (2015) Potent degradation of neuronal miRNAs induced by highly complementary targets
EMBO Rep 16:500-11Ecsedi M, Rausch M Grosshans H (2015) The let-7 microRNA directs vulval development through a single target
Dev Cell 32:335-44Hendriks GJ, Gaidatzis D, Aeschimann F, Grosshans H (2014) Extensive oscillatory gene expression during C. elegans larval development
Mol Cell 53:380-92.Chatterjee S, Grosshans H (2009) Active turnover modulates mature microRNA activity in C. elegans
Nature 461:546-549Ding XC, Grosshans H (2009) Repression of C. elegans microRNA targets at the initiation level of translation requires GW182 proteins
EMBO J 28:213-222Full list of publications
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Stephen grew up near Vancouver in BC, Canada and studied Molecular Biology and Biochemistry at Simon Fraser University. He then went on to do a PhD in Experimental Medicine at McGill University in Montreal, Quebec. During his PhD he studied the molecular mechanisms that generate a diverse antibody repertoire during the immune response.
Wanting to switch gears after his PhD, Stephen moved to the lab of Susan Gasser to study chromatin regulation in C. elegans. He was awarded an EMBO Long Term Fellowship in 2018 to pursue his postdoctoral work with Prof. Gasser.
Current reseachStephen is interested in understanding how chromatin is actively regulated during development and in differentiated tissues. In the Grosshans lab he is using the C. elegans developmental oscillator as a model system to study how dynamic changes to chromatin can regulate rhythmic transcription.
Education• PhD in Experimental Medicine, McGill University, Montreal, Canada
• BSc in Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, Canada
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Alex trained as an engineer specialised in Applied Statistics in Rennes. He obtained a CEA PhD scholarship to work on integrating metabolic and genomic information in prokaryotes. He then worked as a biostatistician for the Sleep/Wake Research Center, before being recruited to bring mouse transcriptomics to the Malaghan Institute of Medical Research. At UNIL, Alex identified lincRNAs involved in the cell cycle. Alex then analysed lipidomics data at the Baker Institute, before becoming a Research Associate at the FMI.
Alex loves to tinker in R and gnaw at datasets until he can get everything out of them, and enjoys helping people out with their experimental designs and statistical analyses.
Alex is helping set up and dig into the many *omics projects of the Grosshans lab, aiming to investigate the molecular clocks driving C. elegans gene expression.
EducationPhD in bioinformatics, Genoscope / Universite Evry Val d'Essonne
Engineering degree, agronomy, specialization in applied statistics,
Agrocampus Rennes
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