Juwon Kim

The novel gene twenty-four defines a critical translational step in the Drosophila clock.

Daily oscillations of gene expression underlie circadian behaviours in multicellular organisms. While attention has been focused on transcriptional and post-translational mechanisms, other post-transcriptional modes have been less clearly delineated. Here we report mutants of a novel Drosophila gene twenty-four (tyf) that show weak behavioural rhythms. Weak rhythms are accompanied by marked reductions in the levels of the clock protein Period (PER) as well as more modest effects on Timeless (TIM). Nonetheless, PER induction in pacemaker neurons can rescue tyf mutant rhythms. TYF associates with a 5′-cap-binding complex, poly(A)-binding protein (PABP), as well as per and tim transcripts. Furthermore, TYF activates reporter expression when tethered to reporter messenger RNA even in vitro. Taken together, these data indicate that TYF potently activates PER translation in pacemaker neurons to sustain robust rhythms, revealing a new and important role for translational control in the Drosophila circadian clock.

Functional Role of CREB-Binding Protein in the Circadian Clock System of Drosophila melanogaster

ABSTRACT Rhythmic histone acetylation underlies the oscillating expression of clock genes in the mammalian circadian clock system. Cellular factors that contain histone acetyltransferase and histone deacetylase activity have been implicated in these processes by direct interactions with clock genes, but their functional relevance remains to be assessed by use of appropriate animal models. Here, using transgenic fly models, we show that CREB-binding protein (CBP) participates in the transcriptional regulation of the Drosophila CLOCK/CYCLE (dCLK/CYC) heterodimer. CBP knockdown in pigment dispersing factor-expressing cells lengthens the period of adult locomotor rhythm with the prolonged expression of period and timeless genes, while CBP overexpression in timeless-expressing cells causes arrhythmic circadian behaviors with the impaired expression of these dCLK/CYC-induced clock genes. In contrast to the mammalian circadian clock system, CBP overexpression attenuates the transcriptional activity of the dCLK/CYC heterodimer in cultured cells, possibly by targeting the PER-ARNT-SIM domain of dCLK. Our data suggest that the Drosophila circadian clock system has evolved a distinct mechanism to tightly regulate the robust transcriptional potency of the dCLK/CYC heterodimer.

Intracellular small interfering RNA delivery using genetically engineered double-stranded RNA binding protein domain

A variety of synthetic carriers, such as cationic polymers and lipids, have been used as nonviral carriers for small interfering RNA (siRNA) delivery. Although siRNA polyplexes and lipoplexes exhibited good gene silencing efficiencies, they often showed serious cytotoxicities, which are not useful for clinical applications. A double‐stranded RNA binding cellular protein with highly specific siRNA binding property and noncytotoxicity was used for siRNA delivery.

Thermodynamic design data and performance evaluation of the water + lithium bromide + lithium iodide + lithium nitrate + lithium chloride system for absorption chiller

Abstract Duhring (P–T–X) and enthalpy-concentration (H–X–T) diagrams of the H2O + LiBr + LiNO3 + LiI + LiCl (mole ratio of LiBr : LiNO3 : LiI : LiCl = 5 : 1 : 1 : 2) system were constructed by using the experimental data sets. Thermodynamic design data for a double-effect series-flow absorption chiller were calculated at various operating conditions [ 2≤Te≤14°C, 30≤Ta≤50°C, 30≤Tc≤50°C, T gh COP =0 ≤T gh ≤T gh (crystallization limit)] by a computer simulation. The proposed working fluid was found to be applicable to cycle operation of air-cooled absorption chiller with no crystallization problem at higher absorber temperature.