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我們目前的研究興趣
Our Current Research Interests

  • 傳統的生物學觀念認為真核生物的染色體是線狀的,原核生物的染色體則是環狀的。1992年我們卻發現鏈黴菌(一類葛蘭氏陽性的土壤細菌)的染色体DNA卻是線狀的。這個發現源自我們針對鏈黴菌染色體不穩定的研究。不穩定的原來是這些線狀DNA的末端區域。鏈黴菌染色體(大約8 Mb長)的不穩定末端區域包括很長(高達數百kb )的顛倒重複序列,以及用共價鍵結合的末端蛋白。

    線狀的細菌染色體在有些重要的生理現象(如複製、接合傳遞、轉位)都無法套用傳統環狀DNA的模型。所以我們必須建立新的模型,研究其生化機制。我們發現染色體(以及線狀質體)DNA的末端帶有很多迴文序列,能夠形成非常奇特的二次結構(如下圖)。這些結構應該和末端DNA的修補複製的機制很有關係。(因為染色体是從中央開始複製,所以末端3'端會留下空隙,須要修補)。

    此外 我們也在研究線狀的染色體與線狀質体在接合生殖過 程中如何地傳送。我們發現與傳統環狀DNA的傳遞模型非常迴異之處。這些奇特的機制可能凸顯線狀DNA演化上獨特的行為,而且能夠用來解釋為什麼這些線狀的染色體所形成的遺傳地圖(genetic map)卻是環狀的。

    鏈黴菌生產多樣的二次代 謝物(包 括大多數的抗笙素),因此是非常重要的工業 微生物。我們也研究 訊號傳導系統參與的抗生素合成的調控,以及鏈黴菌抗藥性的遺傳與生化機轉。此外我們也在研究線狀的染色体是否也存在鏈黴菌之外的其他放線菌科菌種中,特 別一些重要的病源菌(如分枝 桿菌)。 如果這些細菌的染色体也是線狀的話,在基礎研究及實用上都有很大的意義。

    最近我們開始進行鏈黴菌細胞學方面的研究,希望利用新的光學技術了解線狀染色體在活細胞中呈現如何結構,如何複製、以及如何傳送。

  • According the traditional concepts, the eukaryotic chromosomes are linear and the prokaryotic chromosomes are circular. In 1992 we discovered that the chromosomes of Streptomyces (a class of Gram-positive soil bacteria) are linear. This discovery stemmed from our studies on the instability of the Streptomyces chromosomes. The unstable region turned out to be at the termini of the Streptomyces chromosomes. The unstable regions of the chromosomes (about 8 Mb) include terminal inverted repeats of up to several hundreds of kb, and covalently bound terminal proteins.

    The classical models for circular chromosomes cannot be applied to some important physiology of the linear bacterial chromosomes (such as replication, conjugal transfer, and transposition). Therefore, we must improvise new models and investigate new mechanisms. We have found that the termini of the chromosomes (and linear plasmids) contain abundant palindromic sequences capable of forming very special secondary structure (see figure below). These structures should be involved in the patching of the telomeres (Replication of the chromosomal DNA from the inside out would leave gaps at the 3' end that require patching).

    We are also studying how the linear chromosomes and plasmids are transferred during conjugation. We discovered new transfer mechanisms drastically different from those of the classical models. The novel mechanisms probably reflect the behaviors of the linear replicons during evolution, and can also be used to explain why circular genetic maps are generated by these linear chromosomes.

    Streptomyces produce a wide variety of secondary metabolites including the majority of known antibiotics. We have studied the involvement of signal transduction in the regulation of antibiotic biosynthesis, and the genetics and biochemistry of drug efflux in Streptomyces. We are also investigating the possibility that linear chromosomes also exit in actinomycetes other than the streptomycetes, particularly some important pathogens (such as mycobacteria). If these chromosomes are indeed linear, it will be of great significance in basic as well as applied research.

    Recently we initiated cytological studies using modern optical techniques, hoping to understand how the linear chromosomes are structured, replicated, and transferred in life cells.