2007~

  2003~2006

Neuroligins are neuronal cell adhesion molecules located in the postsynaptic membrane of neurons. The mutations of neuroligins are known as one of the causes of autism which show mental retardation and impairment of social interaction. However, little is known about the functions of neuroligins in learning and memory of the intact animals.
To investigate the roles of neuroligins in synaptic plasticity, we suppressed the protein level of neuroligin-1 in the amygdala, a brain region which is highly involved in the etiology of autism, by using lentivirus and investigated the synaptic plasticity by electrophysiological analysis and fear conditioning behavior test.
We found that NMDA receptor-mediated current was reduced in the thalamo-amygdala synapse when we suppressed the neuroligin-1 expression by viral infection. Moreover, long-term potentiation, a synaptic process required for learning and memory, was failed in the neuroligin-1-supressed amygdala. Consistent with the electrophysiological results, neuroigin-1-suppressed rats did now show normal fear memory compared to control rats in the fear conditioning behavior test.
Our results indicated that continuous expression of neuroligin-1 is required for the maintenance of NMDA receptor-mediated synaptic transmission, which enables normal synaptic plasticity and long-term memory in the amygdala of adult animals.

Prof. Nam’s group has found a new gene, FIONA1 that regulates the circadian clock in Arabidopsis. They named the new gene as FIONA referring to the heroine in the famous animation “Shrek”. In this animation, FIONA lives as a human in day and an ogress in darkness with cyclic rhythms. FIONA also sounds similar to “flowering” in Korean. The circadian clock, which controls daily events with the 24h period in organisms, is present as an adaptive and preparatory strategy to the daily cycle of light and temperature. Plants use their circadian clock not only to control daily physiological cycles but also to determine the time when they should flower by measuring the day length. Prof. Nam groups has been searching for genetic elements of the circadian clock system of plants, taking advantage of flowering mutants. As a result, they found that mutation of FIONA1 results in early flowering and an increase in the circadian period length. FIONA1 is a nuclear-localized, central oscillator-associated factor and is conserved in a variety of organisms. The basic elements comprising a circadian cycle are amplitude, period and robustness. Extensive characterization of fiona1 mutant demonstrates that FIONA1 controls the periodic length of circadian rhythm rather than the amplitude and robustness. They also propose a novel concept that the circadian period can be controlled separately from the amplitude and robustness.

Melatonin is a hormone produced by the pineal gland in the brain, which helps to regulate our bodies' circadian rhythm. The rhythmicity of pineal melatonin requires the nocturnal increment of AANAT protein which is a key enzyme in the melatonin biosynthesis pathway. To date, only limited information is available in the critical issue of how AANAT protein expression is up-regulated exclusively at night. We show that the circadian timing of AANAT protein expression is regulated by rhythmic translation of AANAT mRNA. This rhythmic control is mediated by both a highly conserved IRES element within the AANAT 5' UTR and its partner hnRNP Q with a peak in the middle of the night. Consistent with the enhancing role of hnRNP Q in AANAT IRES activities, knockdown of hnRNP Q level elicited a dramatic decrease of peak amplitude in AANAT protein profile parallel to reduced melatonin production in pinealocytes. This translational mechanism is a novel aspect for framing the circadian rhythmicity of vertebrate melatonin, and provides possible cues to develop the therapeutic drugs for sleep disorder-related diseases.

A defective hepatitis B virus (HBV)-specific T-cell response was observed in chronic hepatitis B carriers and considered to be a major determinant of viral persistence. Therefore, an effective immunotherapeutic approach should be capable of generating strong and long-lasting HBV-specific T cell responses. In this study, 12 Caucasian HBV carriers were intramuscularly injected 12 times with HBV DNA vaccine (HB-100) at 4-week intervals in combination with 100 mg of LAM (Epivir-HBV, GlaxoSmithKline) daily for 52 ± 4 weeks and then followed up for another 52 weeks. HBV DNA vaccine contains multiple genes encoding HBV antigens and a genetically engineered human IL-12 mutant as a genetic adjuvant to induce broad and strong immune responses. To evaluate the HBV antigen-specific T cell responses, we performed an ex vivo and cultured IFN-g ELISPOT assay. We observed the restoration of anti-HBV T cel responses by treatment with LAM + HB-100. The observed T cell responses, particularly memory T cell responses could be maintained for at least 40 weeks after the combined therapy and correlated with virological responses, but not with alanine aminotransferase (ALT) elevation. Moreover, DNA vaccination under lamivudine (LAM) treatment appeared to be well-tolerated and showed 50% of virological response rate in CHB carriers. Taken together, combination therapy of the DNA vaccine with chemotherapy may be one of new immunotherapeutic methods for the cure of CHB.