C. elegans lipocalin function in growth factor signaling

University Of Pennsylvania, Philadelphia PA

Investigators

Abstract

Cells use growth factors to communicate with each other and to instruct many different cellular behaviors during animal development. These growth factors must be tightly controlled over space and time to ensure that their instructions reach the appropriate target cells but are not given to inappropriate cells; otherwise, abnormal development will result. This project tests the hypothesis that lipocalins are direct modulators of growth factor signaling. Lipocalins are a large family of proteins found throughout the animal kingdom and implicated in small molecule transport, but their functions are poorly understood. Preliminary studies in the simple invertebrate organism Caenorhabditis elegans suggest that the lipocalin LPR-1 facilitates growth factor signaling during organ development, and may help retain this growth factor near its appropriate target cell. To understand the mechanisms underlying this regulation, the experimental aims are to: 1) Test if LPR-1 directly binds to any or all forms of the growth factor, using a combination of biochemical and transgenic studies; 2) Identify which parts of the LPR-1 protein are important for function, using transgenic studies; and 3) Identify other potential partners of LPR-1, using genetic screens. If LPR-1 acts as proposed, it should bind to the growth factor, and loss of the relevant binding domain should eliminate function. LPR-1 may also bind to other partners that help anchor it in place. These studies will provide significant new insights into how lipocalins function and uncover a novel mechanism of growth factor regulation that may be broadly relevant to other systems. The experiments will establish a new scientific collaboration and the project will provide training activities for a postdoctoral fellow and for multiple undergraduate students interested in scientific careers.