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Chiaolong Hsiao, PhD - Advisor, Loren Williams, PhD
"Molecular Paleontology: A Working Biochemical Model of the Ancestral Ribosome"
In this talk, I will present our recent research on ancient biochemistry. Our focus is the ribosome, which is an macromolecular machine that has been functioning for around 3.5 billion years. We are reconstructing (in silico) and resurrecting (in vitro and in vivo) the ancestral ribosome. Our current model of the ancestral ribosome incorporates ~20% of the extant 23S rRNA and fragments of five ribosomal proteins. We test hypotheses that ancestral rRNA can: (i) assume canonical 23S rRNA-like secondary structure, (ii) assume canonical tertiary structure, (iii) form native complexes with ribosomal protein fragments, and (iv) show peptidyl transferase activity.
Footprinting experiments, Gel shift, spectroscopic, and yeast three-hybrid assays support formation of predicted secondary and tertiary structure, and show specific interactions between ancestral rRNA and ribosomal protein fragments. This robustness suggests that the catalytic core of the ribosome is an ancient construct that has survived billions of years of evolution without major changes in structure. Finally, we will show this ancestral rRNA is capable of catalyzing peptide bond formation.
Sandeep Kumar, PhD - Advisor, Hanjoong Jo, PhD
"Role of Flow-sensitive MicroRNA--miR-712 in Atherosclerosis"
We identified miR-712 as a critical flow-sensitive miRNA in the endothelium. Mechanistically, miR-712 downregulated tissue inhibitor of metalloproteinase-3 (TIMP3) that resulted in activation of downstream metalloproteinases thereby stimulating pro-atherogenic responses (endothelial tubule formation and sprouting) in a flow-dependent manner. Treatment with anti-miR-712 reduced plaque formation in two different murine models of atherosclerosis.