Cold-shock Adaptation - When E. coli cells are exposed to low temperatures, a number of cytoplasmic proteins (cold-shock proteins) are specifically induced. Among them, CspA. CspB and CsrA have been extensively studied in our laboratory. Our data indicate that CsrA is a new ribosomal protein which functions as an ATP-dependent RNA helicase to unwind stable secondary structure in mRNAs formed at low temperatures. CspA is an RNA chaperone which prevents the formation of secondary structures in mRNA, and CspB is a DNA chaperone which plays an important role in transcription as well as in DNA replication.
Osmoregulation and Transmembrane Signal Transduction - Adaptive responses of E. coli to medium osmolarity provides an ideal system in which to study signal transduction across the membrane as well as the transcriptional regulation of two porin genes (ompF and ompC) by a transcriptional factor (OmpR). Its function is modulated by a transmembrane signal transducer (EnvZ) which functions not only as kinase but also as phosphatase for OmpR.
Molecular Biology of Aging - One of the major causes of aging is known to be oxidative damage due to various oxidants produced during respiration. We have constructed transgenic mice overexpressing human glutathione peroxidases and superoxide dismutase to study oxidative stress on aging and the effect of antioxidant enzymes on radical-generation chemicals and carcinogens.
Development of Myxococcus xanthus - M. xanthus is a Gram-negative bacterium which can undergo cellular differentiation upon nutrient starvation. M. xanthus provides an excellent system in which to study the morphogenesis and molecular mechanism of control of gene expression during development. Attempts are being made to characterize several development-specific proteins. including a number of eukaryotic-like protein serine/threonine kinases.
GTP Metabolism - GTP plays key roles in various cellular functions. We are investigating a number of GTP-associated proteins in E. coli such as Era (an essential GTP-binding protein of unknown function), EF-Tu, and nucleoside diphosphate kinase.
Protein Folding - We are attempting to decipher the precise process of protein folding by molecular genetic as well as biochemical approaches using pro-subtilisin as a model system. In this system the propeptide of 77 amino acid residues functions as an intramolecular chaperone which is essential for the folding of active subtilisin.
Bacterial Retroelements - About 10% of the natural population of E. coli contain a highly diverse retroelement called 'retron', which is responsible for the production of a peculiar RNA-DNA complex (msDNA). We are attempting to determine the biological function of the retron, the biosynthetic mechanism of msDNA, and to search for its origin.