In vivo functional analysis of dDRP

• Applicant: Professor Dr. Aurelio A. Teleman
• Subject Area: Developmental Biology
• Term: from 2010 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 167441013

A fundamental yet unresolved problem in developmental biology is the question of how developing, growing tissues know when they have reached their correct final size and therefore should stop growing. Although the signaling pathways responsible for regulating tissue growth are beginning to be elucidated, many components of these pathways remain to be discovered. In order to drive tissue growth, these pathways need to up-regulate cellular translation, in order for cells to produce the necessary proteins to gain mass. Therefore, components that regulate cellular growth and proliferation by controlling translation are of particular interest. This proposal aims to study one such protein, called Density Regulated Protein (DRP). DRP was identified in human cell culture as a protein that interacts with components of the translational machinery, and has a domain found in translation initiation factors. However, no functional studies on DRP have been done, so that the function of DRP, either in cells or in an organism, is unknown. We have generated DRP knockout flies, and have phenotypically characterized them. DRP mutants are semi-lethal and display a number of specific defects indicating DRP plays a role in proliferation control and growth. These include abdominal malformations also seen in mutants for cell-cycle regulators, as well as wings and legs of reduced size. Furthermore, we find that histoblast cells, which grow to form the adult abdominal epithelium, do not proliferate properly in DRP knockouts. Therefore, our preliminary work indicates DRP functions to regulate tissue growth and proliferation. We propose here to exploit the tools we have generated to study the molecular function of DRP. This should yield new insight into how translational regulation controls tissue growth and tissue size.

• DFG Programme: Research Grants