Helge Grosshans

Group News

Apr 13, 2021
When two worlds meet: a protease that controls small RNA activity
Jul 21, 2020
A developmental clock with a checkpoint function
Apr 5, 2020
The circuitous path to adulthood
Aug 5, 2019
Unlocking the secrets of an important regulator of human development
Mar 26, 2019
Über die Pubertät weiss man jetzt mehr – dank einem winzigen Wurm
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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, e201900335

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

Miki 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 16:500-11

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.

Katic I, Grosshans H (2013) Targeted heritable mutation and gene conversion by Cas9-CRISPR in Caenorhabditis elegans

Genetics 195:1173-6

Chatterjee S, Fasler M, Büssing I, Grosshans H (2011) Target-mediated protection of endogenous microRNAs in C. elegans

Dev Cell 20:388-396

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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Members

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 2018
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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 2014
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In current position since 2021
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In current position since 2019
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In current position since 2018
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In current position since 2021
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ORCID

Biography

Abhi is from central India where he studied Biotechnology Engineering. His first research project was to investigate multicellularity in social amoebae. He went on to receive a full scholarship for a research-based masters in Marine Biology in Hong Kong, performing experiments on larvae and shell proteins of an intertidal oyster. His stint in South Africa concerned evolvability at the origin of cellular life. For his theoretical PhD in Systems Biology, he moved to Germany where he mathematically modelled the molecular switches and rhythms in the circadian clock of a filamentous fungi.

Current reseach

Abhi is combining experimental and theoretical approaches to elucidate the regulatory network underlying a developmental clock of C. elegans.

Education

PhD in Theoretical Chronobiology, Humboldt University of Berlin (in collaboration with Heidelberg University)
Predoc in Evolutionary Biology, Wits University
MPhil in Marine Biology, University of Hong Kong
Premaster in Developmental Biology, Indian Institute of Science
BEng in Biotechnology Engineering


Technical/Research associates

In current position since 2015
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In current position since 2021
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In current position since 2018
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In current position since 2021
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Undergraduates

In current position since 2021
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Visiting scientists

In current position since 2019
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Alumni

PhD students

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

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

Monika Fasler (2005-2015)
Mirela Vitanescu (2010-2014)

Undergraduates

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)

Education

2001
PhD, University of Heidelberg, Heidelberg, Germany
1997
Dipl-Biotechnol, University of Braunschweig, Braunschweig, Germany

Positions held

2011-
Senior Group Leader, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
2005-2011
Junior Group Leader, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
2001-2005
Postdoctoral Fellow, Yale University, New Haven, USA

Honors

2009
European Research Council (ERC) Starting Independent Researcher Award
2003
Keystone Symposium Scholarship
2002-2005
Human Frontier Science Program, Postdoctoral Fellowship
2002
Theresa Seessel Postdoctoral Fellowship, Yale University
2001
Schering Forschungsgesellschaft, Postdoctoral Fellowship (gratefully declined)
2001
EMBO Postdoctoral Fellowship (gratefully declined)