Chemical modifications occur widely in nucleic acids and exert important regulatory functions in biology. Chemical modifications can change electrostatics, hydrophobicity, steric hindrance, and hydrogen bonding propensity of the modified moieties (i.e. nucleobase and sugar-phosphodiester backbone), and thus alter nucleic acids structure, stability, and interactions with surrounding molecules. Dysregulations of the chemical modification landscapes and their effector proteins have been found closely relevant in abnormal cellular functions, development disorders, and diseases.
The Zhou research group focuses on developing and applying new technologies to visualize spatial and temporal distributions of chemical modifications in the mammalian transcriptome at base-resolution, studying molecular mechanisms of how chemical modifications and their regulatory network control gene expression, and developing tools to modulate transcript-specific RNA modification level in order to revert dysregulated epitranscriptome in diseases. Projects in the Zhou lab take interdisciplinary approaches including directed evolution, protein engineering, RNA and enzyme biochemistry, mass spectrometry, next-generation sequencing, bioinformatics, and structural biology. Ultimately, research in the Zhou lab aims to achieve an in-depth understanding of regulatory mechanisms of epitranscriptome that can lead to discoveries of novel drug targets and diversify the toolbox of gene therapy.