Helge Grosshans
Group News
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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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Aug 5, 2019 Unlocking the secrets of an important regulator of human development |
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Mar 26, 2019 Über die Pubertät weiss man jetzt mehr – dank einem winzigen Wurm |
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Mar 25, 2019 A key player in the maturation of sexual organs |
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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, 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)
Aeschimann, F., Neagu, A., Rausch, M., and Grosshans, H. (2019) A single let-7 target to coordinate transition to adulthood
Life Science Alliance 2, e201900335Brancati, G., and Grosshans, H. (2018) An interplay of miRNA abundance and target site architecture determines miRNA activity and specificity
Nucleic Acids Res. 46: 3259-3269Miki TS, Carl SH, Grosshans H (2017) Two distinct transcription termination modes dictated by promoters
Genes Dev. 31: 1870-1879.Aeschimann 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.Katic I, Grosshans H (2013) Targeted heritable mutation and gene conversion by Cas9-CRISPR in Caenorhabditis elegans
Genetics 195:1173-6Chatterjee S, Fasler M, Büssing I, Grosshans H (2011) Target-mediated protection of endogenous microRNAs in C. elegans
Dev Cell 20:388-396Chatterjee 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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