Dominick DiMercurio

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  Student Presentation: Simulated and Experimental Effects of RNA Interference on Cell Motility
  Dominick DiMercurio, Pranjal Singh

  Cell migration is a critical and recurrent phenomenon in animal biology; migration is a key feature in wound healing, immune function, and embryo development. In particular, egg chamber developmental stages in Drosophila melanogaster, a model organism for human genetics, provide a suitable opportunity to investigate migratory regulation. An important process in oogenesis is when the epithelial border cells on the anterior end of the egg chamber move toward the oocyte. A key molecular pathway in this process involves the uptake of the ligand Unpaired by follicle cells, which causes the signaling molecule Signal Transducer and Activator of Transcription (STAT) to activate transcription of downstream targets that promote migration. In genetic analyses of D. melanogaster ovaries that had reduced STAT expression via RNA interference (RNAi), we reproduced phenotypes of partially delayed or completely inhibited migratory behaviors compared to sibling controls. To investigate this phenomenon mathematically, we used a previously derived system of differential equations that modeled the signaling pathway, reduced the system with simplifying assumptions, and introduced a parameter to account for the effect of RNAi on mRNA that encoded STAT. Through computational methods, we simulated time courses of select proteins and created a bifurcation diagram of their steady states. Moving forward, research into this process could examine the biological bases for temporal variation in RNAi-based effects on protein expression as predicted in our mathematical models. This research will help biologists obtain a better understanding of mechanisms for cell migration, which may itself lead to insights on migratory pathways for the metastasis of cancer and the occurrence of other developmental defects.

  
  

  
  

  This work was funded in part through an Undergraduate Biology Mathematics (UBM) Research Award from the National Science Foundation under Grant No. DBI 1031420, PIs Drs. Leips and Neerchal.