Post-translational control of cell fate decisions

Project Details

Cell fate decisions are fundamental during the development of multicellular organisms. They affect all aspects of a cell’s behaviour including morphology, migration, proliferation, and specialized functions such as contraction, detoxification, and hormone production and are therefore the foundation for the development of a multicellular organism. Arguably, one of the most unique cell fate decisions during mammalian development forms the basis of male vs. female identity. While progress has been made in understanding the role of transcriptional regulation, the influence of post-translational modification is poorly understood.

We have shown that NEDD4-mediated ubiquitination is absolute necessary for mammalian sex determination. In this project we are testing the hypothesis that post-translational modifications, and specifically ubiquitination, control cell fate decisions that play a critical role in sex development.

The understanding of the post-translational modification in the regulation and function of gonad-specific proteins will contribute to advance our understanding of cell fate decision during gonad development and will ultimately inform about post-translational regulation driving organogenesis, cell fate decisions and cellular reprogramming during embryonic development.

Researchers

Simon Windley, PhD student

Collaborators

Prof Sharad Kumar, Centre for Cancer Biology, Adelaide
Dr Quenten Schwarz, Centre for Cancer Biology, Adelaide
Dr Natasha Harvey, Centre for Cancer Biology, Adelaide
A/Prof Serge Nef, University of Geneva, Switzerland

Funding

ARC Discovery grant: “Post-translational control, of cell fate decisions”

Research Publications

  • Callier P, Calvel P, Matevossian A, Makrythanasis P, Bernard P, Kurosaka H, Vannier A, Thauvin-Robinet C, Borel C, Mazaud-Guittot S, Rolland A, Desdoits-Lethimonier C, Guipponi M, Zimmermann C, Stevant I, Kuhne F, Conne B, Santoni F, Lambert S, Huet F, Mugneret F, Jaruzelska J, Faivre L, Wilhelm D, J├ęgou B, Trainor PA, Resh MD, Antonarakis SE, Nef S. Loss of function mutation in the palmitoyl-transferase HHAT leads to syndromic 46,XY disorders of sex development by impeding Hedgehog protein palmitoylation and signaling. PLoS Genetics 2014; 10: e1004340
  • Bannister AJ, Oehler T, Wilhelm D, Angel P, Kouzarides T. Stimulation of c-Jun activity by CBP: c-Jun residues Ser63/73 are required for CBP induced stimulation in vivo and CBP binding in vitro. Oncogene 1995; 11: 2509-2514.
  • Wilhelm D, van Dam H, Herr I, Baumann B, Herrlich P, Angel P. Both ATF-2 and c-Jun are phosphorylated by stress-activated protein kinases in response to UV irradiation. Immunobiol 1995; 193: 143-148.
  • van Dam H, Wilhelm D, Herr I, Steffen A, Herrlich P, Angel P. ATF-2 is preferentially activated by stress-activated protein kinases to mediate c-Jun induction in response to genotoxic agents. EMBO J 1995; 14: 1798-1811.

Research Group

Wilhelm laboratory: Sex determination and disorders of sex development



Faculty Research Themes

Child Health

School Research Themes

Molecular Mechanisms of Disease



Key Contact

For further information about this research, please contact the research group leader.

Department / Centre

Anatomy and Neuroscience