Martinez-Arias Lab

Department of Genetics, University of Cambridge

Ulla-Maj Fiuza

PhD student

umf20@mole.bio.cam.ac.uk
Department of Genetics,
Downing Street, Cambridge
CB2 3EH,England
Telephone: +44 1223 766742
Fax: +44 1223 333992

Notch signalling is a short range cell-cell communication system. It plays a crucial role in processes of binary cell fate decisions during development, which underlie events of cell differentiation, patterning and boundary formation as well as the maintenance of stem cell populations in adult organisms. Notch signalling has very precise patterns of activity whether considering the time or periodicity of activation or the localization of the activity. This is ensured by several strategies involving protein-protein interactions, gene expression regulation and post-transcriptional modifications. Recent studies have uncovered a role for intracellular traffic in the regulation of Notch activation. Regulation of cis and trans interactions between Notch and its ligands play an important role in this.

I am interested in the regulation of Notch signalling activity and am looking at how different proteins can affect the general mechanisms of Notch activation. This aim is being approached by studying the interactions between Notch and its ligands (Delta and Serrate), trying to identify new Notch extracellular binding partners, looking at effects of Wingless (Wg) on Notch signalling and exploring the regulatory activity of Notch extracellular regions.

In order to better understand the mechanisms of activation and modulation of Notch signalling activity mediated by extracellular Notch, I am exploring the nature of the interactions between Notch and its ligands. Delta and Serrate in addition to a trans activating effect have an inhibitory effect. I have been using a combination of reporter assays, cell imaging and in vivo analysis in Drosophila, to characterize the ligand inhibition mechanism. I am using phage display technology to identify new Notch interacting partners that could have a regulatory role. To look at possible effects of Wg on Notch signalling I am using reporter assays aimed to distinguish between effects caused by the Wg molecule and by the Wg signalling pathway. I am also exploring the role of the Abruptex region (from a class of notch mutants containing mutations in the EGF-repeat 24-29 region) and other regions of extracellular Notch. This is aimed to try to understand both the phenotypes exhibited by the Abruptex class of notch mutants and also to explore how an extracellular region not directly involved in the ligand-Notch trans interaction can affect properties of Notch signalling activity.

Reporter assay system with Notch signalling activity triggered by EDTA treatment.

S2 cells expressing Delta at the cell surface.

Notch signalling activity with dppGal4 UASGFP, UASECNΔ10–12 expression seen by the expression of Notch target gene Cut (red).

Publications

Fiuza UM, Martinez Arias A, (2007)
Cell and molecular biology of Notch, Journal of Endocrinology, 194(3):459-74.