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ดร.ศรินทร์ ฉิมณรงค์
รองศาสตราจารย์

We utilized unique RNA-centric approaches to study RNA–protein interactions happening during dengue virus infection to understand disease mechanism and develop antiviral therapy.

     Less than 3% of the human genome encodesproteins, and more than half of the transcripts in human appear to be non-coding (nc) RNAs. This fact redefined the paradigm of genetic flow (The Central Dogma), and shed light on the hidden roles of ncRNAs in regulation of cellular processes. There are likely to be many more unknown ncRNAs that are fulfilling a wide range of unexpected functions in eukaryotic biology.

     Given that ncRNAs require formation of the ribonucleoprotein (RNP) complexes to be functional, our studies are focusing on the interaction interfaces between proteins and ncRNAs (RNPomics). In particular, we performed genome-wide searches for the RNP interfaces between dengue viral RNA and human factors, and discovered the RNA promoter motif in dengue genomic RNA for the first time. We are attempting to inhibit this interface for the development of anti-dengue therapy. Our researches are discovery-based, and employ multidisciplinary approaches from genetic screen, bioinformatics,in vitro analysis, cell-based assays, to X-ray crystallographic analysis of 3D structure of RNP molecules. We own several modern methodology such as the yeast three-hybrid system, random mutagenesis, RNA-binding assays, RNA cross-link immunoprecipitation (CLIP), and RNP crystallization. We are also trying to develop novel system to globally identify the target genes of miRNAs in eukaryotes. We aim to perform unique, outstanding, and high-impact researches in Thailand.

1.Tunghirun C, Narkthong V, Chaicumpa W, Chimnaronk S. (2020) Interference of dengue replication by blocking the access of 3´ SL RNA to the viral RNA-dependent RNA polymerase. Antiviral Res. In press.

2.Hodge K, Tunghirun C, Kamkaew M, Limjindaporn T, Yenchitsomanus PT, Chimnaronk S. (2016) Identification of A Conserved RdRp-RNA Interface Required for Flaviviral Replication. J Biol Chem. 291(33), 17437-49.

3.Poyomtip T., Hodge K., Matangkasombut P., Sakuntabhai A., Pisitkun T., Jirawatnotai S., Chimnaronk S. (2016) Development of viable TAP-tagged dengue virus for investigation of host-virus interaction in viral replication. J Gen Virol. 97(3), 646-58.

4.Kamkaew M., Chimnaronk, S. (2015) Characterization of soluble RNA-dependent RNA polymerase from dengue virus serotype 2: The polyhistidine tag compromises the polymerase activity. Protein Expr Purif. 112, 43-9.

5.Choksupmanee O., Hodge K., Katzenmeier G., Chimnaronk S. (2012) Structural platform for the autolytic activity of an intact NS2B-NS3 protease complex from dengue virus. Biochemistry. 51, 2840-51.

pubmed
Thai Government Scholarship (ทุน ก.พ.)