Ribosomes are essential for all cellular processes, and because ribosomal proteins must be produced in equal quantities, their expression is tightly regulated. My recent research has pointed to a new class of highly conserved elements in the upstream regions of ribosomal protein genes (RPGs) in Caenorhabditis elegans (1,2). However, the regulatory mechanisms that control the expression of these genes is poorly understood in most species. The goal of the current project is to investigate gene regulation with respect to RPGs in the nematode C. elegans. .For the proposed project, I have already found 10 novel conserved motifs in the upstream regions of C. elegans cytoplasmic RPGs. Most of the motifs were not similar to any previously described transcription factor binding sites, and four of them were similar to motifs found in the previous investigation. One pair of motifs was found to co-occur in a significant number of upstream regions; in all co-occurrence cases, these two motifs appeared within 60bp of each other, forming a striking pattern. In C. elegans, the 5’ untranslated region of many protein-coding messenger RNAs is replaced with a short conserved RNA in a process called trans-splicing. The trans-splice sites of RPGs were found to be significantly different from those of other genes. I will continue to investigate these motifs and trans-splice sites by determining how strongly they are conserved in other nematode genomes and by examining all genes that are associated with the motifs..I will determine the function of the motifs by performing Green Fluorescent Protein expression assays. These assays will be done in collaboration with Professor Chen Runsheng at the Institute of Biophysics, Chinese Academy of Sciences (陈润生院士, 中国科学院生物物理研究所). In the future I intend to form collaborations with other scientists such as Dr. Marian Walhout of the University of Massachusetts in order to determine which proteins bind to the motifs. The results of these experiments will lead to the discovery of a novel mechanism of gene regulation for this important group of genes. .Many transcription factors in C. elegans have orthologues in the human genome, which have similar binding specificities, so information from this study could be directly applicable to human gene regulation. I intend to lead a group of students to pursue these results and continue the bioinformatic investigation of conserved elements in C. elegans and other genomes. In the future, I want to start my own C. elegans laboratory at Tsinghua University with the goal of becoming a principal investigator of the regulation of ubiquitously expressed genes and of the function of highly-conserved genomic elements in nematodes..References:.1..Sleumer MC, Bilenky M, He A, Robertson AG, Thiessen N, Jones SJM (2009) Nucleic Acids Res., 37:1323-34..2..Sleumer MC, Mah AK, Baillie DL, Jones SJM (2010) Nucleic Acids Res., 38:2990-3004.