Developmental Biology
Eugenia Piddini 
Research Fellow, The Wellcome Trust/CR UK Gurdon Institute
Email: e.piddini@gurdon.cam.ac.uk
Tel.: +44 (0)1223 334114
Competitive cell interactions in normal physiology and cancer
In order to generate and maintain healthy tissues and organs, cells communicate to coordinate decisions such as whether to proliferate, differentiate or die. Our lab’s work aims to elucidate how cells interact to achieve such coordination and how that coordination goes awry in diseases such as cancer.
Previous work in the fly Drosophila has shown that, in wing imaginal discs, cells compete for survival and cells sensed as weaker or less fit are induced to die, in a phenomenon called cell competition . We have recently found that cells with different signalling levels of the growth factor Wingless (the Drosophila homolog of the mammalian Wnt family oncogene Wnt-1) engage in cell competition in wing discs and, in particular, that cells with abnormally high signalling levels induce the death of neighbouring wild-type cells. Since Wnt signalling is overactivated in a variety of cancers, Wnt-induced cell competition could allow cancer cells to kill surrounding normal cells during early tissue colonization.
Based on these observations, our current work is expanding in two main directions. First, we want to understand at the molecular level how this newly discovered type of competition is brought about. To this end, we are using the power of Drosophila genetics to investigate how cells sense differential Wingless signalling levels among them, and what molecules they exchange that lead to the selective elimination of low Wingless signalling cells. Secondly, we want to investigate the relevance of this phenomenon beyond Drosophila. For that purpose, we will aim to reconstitute Wnt-induced cell competition between normal and transformed/tumour-derived mammalian cells in culture. This will allow us to translate our findings from Drosophila to mammals and to study competition under more controlled experimental conditions.
Future projects will exploit and build on this dual approach to look for novel cellular competition pathways and dissect their mechanisms of action.
Selected publications
- Vincent JP, Kolahgar G, Gagliardi M, and Piddini E. (2011). Steep differences in wingless signaling trigger myc-independent competitive cell interactions. Dev Cell 21, 366-374.
- Piddini E and Vincent JP (2010) Steep differences in Wingless signalling trigger Myc-independent competitive cell interactions. [submitted]
- Hogan C, Dupré-Crochet S, Norman M, Kajita M, Zimmermann C, Pelling AE, Piddini E, Baena-López LA, Vincent JP, Itoh Y, Hosoya H, Pichaud F and Fujita Y (2009) Characterisation of the interface between normal and transformed epithelial cells. Nat Cell Biol 11(4):460-7
- Piddini E and Vincent JP (2009) Interpretation of the Wingless gradient requires signalling-induced self-inhibition. Cell 136, 296-307
- Piddini E*, Marshall F*, Dubois L, Hirst E and Vincent JP (2005) Arrow (LRP6) and Frizzled2 cooperate to degrade Wingless in Drosophila imaginal discs. Development 132(24), 5479-89
- Franch-Marro X, Marchand O, Piddini E, Ricardo S, Alexandre C and Vincent JP (2005) Glypicans shunt the Wingless signal between local signalling and further transport. Development 132(4), 659-66
* denotes equal contribution
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