Introduction
    Research interests

    Our laboratory studies the genetic bases of the intrinsic cell defense systems against pathogenic bacteria and their virulence factors. We apply chemical genomic, forward/reverse genetic, CRISPR/Cas9 genome editing, molecular and biochemical methodologies, and the model organism Caenorhabditis elegans to elucidate the conserved mechanisms in host-pathogen interactions. The advantage of using C. elegans as a host-pathogen model includes: 1) This organism has a short 2-3 weeks life span; 2) It has a relative small and fully sequenced genome which can facilitates genetic and genomic analysis; 3) A wealth of data has demonstrated that a variety of developmental, neurological, cell biological and biochemical processes have been highly conserved between this simple model organism and mammals. Moreover, a rapidly growing number of human and animal microbial pathogens have been shown to infect and kill C. elegans. In many cases, microbial genes known to be essential for full virulence in mammalian models have been shown to be similarly required for maximum pathogenicity. Since the innate immune responses are highly conserved among different organisms throughout evolution, understanding the molecular basis of the intrinsic cell defense systems in C. elegans should shed light onto some aspects of immunity in Human diseases.

    研究主軸

    本實驗室主要運用線蟲(C. elegans)作為模式生物,來研究致病細菌及其致病因子之病源與宿主間之交互作用(pathogen-host interaction)。我們主要運用:化學基因體學、遺傳學篩選、CRISPR/Cas9 基因體編輯、分子及生物化學等方法來探索病源與宿主交互作用之生物訊息傳遞以及致病機制。

    線蟲被運用於分子生物學、細胞生物學、神經生物學與發育生物學之研究已有數十年之久,這個世紀以來已有兩組線蟲科學家因利用此一模式生物對計畫性細胞死亡(programmed cell death)及干擾性核醣核酸(RNA interference)生物機制的研究而獲頒諾貝爾生醫獎,以及研究在活體表現綠色螢光蛋白(Green fluorescent protein)的運用而獲得一次的諾貝爾化學獎的殊榮,顯示線蟲在尖端生物技術的開發與生命現象的深入探索,皆具有其他生物材料所不可取代的優勢。

    近年來以線蟲作為模式生物來研究致病菌之致病機制也正快速發展中。在許多研究中發現,許多致病菌在感染哺乳類宿所需的致病因子,也同樣被用於對線蟲之致病過程,而且線蟲之細胞以及先天性免疫反應(innate immunity)也與哺乳類細胞具有很高的相似性。因為先天性免疫反應在演化的過程中具有相當高的保留性,我們相信經由對線蟲的研究或許我們可以對人類感染性疾病之免疫反應有更進一步的了解。