Helge Grosshans

Group News

Feb 22, 2024
Largest study of developmental microRNA dynamics uncovers mechanism of their regulation
Jun 27, 2023
Molecular ‘hub’ regulates gene-silencing proteins
Jan 23, 2023
Identified: components of the molecular clock that helps some animals shed their skin
Jun 7, 2022
How animals reach their correct size
Apr 13, 2021
When two worlds meet: a protease that controls small RNA activity
All group news


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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.

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:e111895

Gudipati, 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.e8

Tsiairis, 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 19-43

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)

Brancati, G., and Grosshans, H. (2018) An interplay of miRNA abundance and target site architecture determines miRNA activity and specificity

Nucleic Acids Res. 46: 3259-3269

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 16:500-11

Ecsedi M, Rausch M Grosshans H (2015) The let-7 microRNA directs vulval development through a single target

Dev Cell 32:335-44

Hendriks 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 461:546-549

Ding XC, Grosshans H (2009) Repression of C. elegans microRNA targets at the initiation level of translation requires GW182 proteins

EMBO J 28:213-222

Full list of publications
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Group leader

In current position since 2005
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PhD students

In current position since 2017
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In current position since 2023
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In current position since 2023
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In current position since 2022
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In current position since 2019
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In current position since 2019
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Postdoctoral fellows

In current position since 2023
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In current position since 2021
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Google scholar


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 reseach

Stephen 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.


• PhD in Experimental Medicine, McGill University, Montreal, Canada
• BSc in Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, Canada

In current position since 2019
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Technical/Research associates

In current position since 2015
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In current position since 2021
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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.

Current reseach

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.


PhD in bioinformatics, Genoscope / Universite Evry Val d'Essonne
Engineering degree, agronomy, specialization in applied statistics,
Agrocampus Rennes

In current position since 2018
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PhD students

Maike Graf (2018-2023)
Chiara Azzi (2016-2021)
Saheli Roy (2019-2021)
Yannick Hauser (2015-2020)
Milou Meeuse (2015-2020)
Giovanna Brancati (2013-2018)
Florian Aeschimann (2011-2016)
Gert-Jan Hendriks (2012-2016)
Hannes Richter (2010-2015)
Hrishikesh Bartake (2010-2015)
Magdalene Rausch (2009-2014)
Stefan Rueegger (2009-2014)
Matyas Ecsedi (2009-2013)
Benjamin Hurschler (2006-2011)
Xavier Ding (2005-2009)
Almuth Muellner (2006-2008)

Postdoctoral fellows

Smita Nahar (2018-2023)
Maike Graf (2023)
Abhishek Upadhyay (2021-2022)
Rajani Gudipatti (2014-2021)
Foivos Gypas (2019-2021)
Yannick Hauser (2020)
Milou Meeuse (2020)
Thomas Welte (2017-2019)
Benjamin Towbin (2016-2019)
Jun Liu (2015-2019)
Giovanna Brancati (2018)
Florian Aeschimann (2017-2018)
Takashi Miki (2011-2017)
Gert-Jan Hendriks (2016)
Manuel De la Mata (2012-2015)
Magdalene Rausch (2014-2015)
Stefan Rueegger (2014)
Nicolas Antih (2010-2013)
Saibal Chatterjee (2007-2012)
Ingo Buessing (2005-2011)

Technical/Research associates

Alison Goulois (2021-2023)
Monika Fasler (2005-2015)
Mirela Vitanescu (2010-2014)


Irenaeus Stec (2023)
Dennis Umgelter (2023)
Irenaeus Stec (2022-2023)
Julien Orguel (2021-2022)
Andrea Pedroni (2019)
Carolin Warnecke (2019)
Max Golubowski (2016-2017)
Chiara Azzi (2016)
Nicole Pina (2015)
Yannick Hauser (2013-2015)
Simon Muehl (2014)
Melanie Hunkeler (2009-2011)
Lysie Champion (2007-2009)
Keovilay Chanthavinout (2006)

Visiting scientists

Thomas Welte (2019-2023)


PhD, University of Heidelberg, Heidelberg, Germany
Dipl-Biotechnol, University of Braunschweig, Braunschweig, Germany

Positions held

Senior Group Leader, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
Junior Group Leader, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
Postdoctoral Fellow, Yale University, New Haven, USA


European Research Council (ERC) Starting Independent Researcher Award
Keystone Symposium Scholarship
Human Frontier Science Program, Postdoctoral Fellowship
Theresa Seessel Postdoctoral Fellowship, Yale University
Schering Forschungsgesellschaft, Postdoctoral Fellowship (gratefully declined)
EMBO Postdoctoral Fellowship (gratefully declined)