Professor Wu Develops a Tool That Contributes to Major Breakthrough in C.elegans Research
成大電機系教授吳謂勝開發利器,助線蟲研究突破
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        As a C.elegans researcher, Professor Wei-Sheng Wu at the Department of Electrical Engineering in National Cheng Kung University recognized the need for a fast and user-friendly tool to aid in C.elegans research. With his master’s student Wei-Che Huang, he thus developed the web tool piScan and helped a research team in Chicago make a breakthrough. They now have the chance to solve a genetic mystery that has baffled C.elegans researchers for more than two decades. Their achievements are published in the February issue of Science in 2018, and the article is expected to capture the attention of C.elegans researchers around the world and exert a significant impact.

        The corresponding author of this article in Science, “The piRNA targeting rules and the resistance to piRNA silencing in endogenous genes”, is Professor Heng-Chi Lee of the University of Chicago, and Professor Wu and Wei-Che Huang are co-authors. Professor Wu is devoted to designing bio-databases and developing bioinformatics web tools. Unable to tolerate things that cannot be used or understood, he insists that all of the tools produced in his laboratory must be “simple, functional, but not fancy.” Users only need to open a webpage, choose the settings, and execute. They do not need to install any programs and can obtain results even for people who cannot write any programs.” These tools are exactly what researchers have wanted.

        Wu originally specialized in communication systems in graduate school. While pursuing his doctorate degree, however, he decided to follow his mentor, Professor Bor-Sen Chen at the Department of Electrical Engineering in National Tsing Hua University, to cross over into the field of systems biology. By continuously improving himself and his expertise, Wu was able to accumulate enough biological knowledge, and he immediately hit it off with Lee. “We met at a Chinese New Year party held by the University of Chicago Taiwanese Student Association in the January of 2017. Maybe it was because we were both Taiwanese; we decided to collaborate really quickly. Heng-Chi Lee is a post-doctor of Nobel Prize winner Craig Mello. If you don’t have a strong background in biology, you won’t understand what he wants. It was just the perfect conditions for this international collaboration.”

        Wu indicated that there is new knowledge to be gained every day. All modern biologists will have to conduct big data analyses at one time or another to derive further conclusions, which makes program development even more important. He regards the development of each program as a process of giving birth to new life and exercises utmost care. In regards to Wei-Che Huang, who was responsible for writing the program, Wu expressed strong praise. “He contributed enormously to this project. He originally had no experience at all but overcame a number of difficulties through self-learning.”

        Mild-mannered and reserved, Huang never imagined that his accomplishments would be published in Science. He jokes that he is most thankful for Professor Wu breaking down his neck all the way. “Professor Wu is really different. Most of the time, grad students only see their advisors during meetings, but Professor Wu is at the lab checking our progress and discussing things with us every day, sometimes even on holidays.” With strict and meticulous Wu as his advisor, Huang admitted that there were agonizing days, but he never thought about quitting. Feeling fortunate to have undergone such training, he has gained a strong sense of accomplishment.

        Even before its official launch, piScan has already received much attention from C.elegans researchers. Wu indicated that C.elegans researchers have been trying to use reporter genes in the past but were hindered by piRNA recognition, an intracellular defense mechanism. This problem has confronted C.elegans researchers for more than 20 years. Lee found the targeting logic of piRNA in C.elegans to explain why foreign nucleic acids are generally silenced after entering C.elegans germline cells. With piScan, the nucleic acid sequences of fluorescent protein can be changed to escape piRNA targeting, which results in the successful fluorescent protein expression. Thus, C.elegans researchers will be able to insert the nucleic acid sequences that they want to be expressed in C.elegans. In other words, based on the targeting rules of piRNA, researchers can successfully find the sequences they want to be expressed and modify them. “What originally could not be expressed could now successfully be expressed. This is a major breakthrough for biologists.”

        As stated in Issue 555 of the Science Monthly, “There are more than 10,000 papers on C. elegans, and six scientists have received Nobel Prizes for research on C.elegans”. This shows that there are numerous C.elegans researchers, and Wu’s achievement will assist them in solving more mysteries in C.elegans genetics.

        成大電機工程系教授吳謂勝帶領碩士班學生黃偉哲,站在使用者角度了解線蟲生物學家需求,「要人性化、速度也要夠快」,順利開發出簡便好用的網頁工具piScan,協助芝加哥大學研究團隊找到突破關鍵,可望解開困擾線蟲生物學家20多年的序列謎團,研究成果登上2018年2月《Science》期刊,預期將受到全球線蟲生物學家關注,極具影響力。

        這篇榮登《Science》的論文「The rules for piRNA targeting reveal resistance of endogenous genes to piRNA silencing in C. elegans」,通訊作者是美國芝加哥大學李亨啓教授,吳謂勝與黃偉哲為共同作者。吳謂勝教授擅於設計生物資料庫及開發生物資訊網頁工具,「無法容忍看不懂或不能用的狀況」,所有出自他實驗室的工具,一定要「簡單、功能到位但不花俏,只要會使用瀏覽器開啟網頁,選按條件、執行,不需要安裝程式,即使電腦程式功力不佳,也能透過這個工具獲得結論。」完全說中使用者心聲。

        原本碩士班專長在通訊的吳謂勝,唸博士班時毅然決然跟隨恩師清大電機系陳博現教授跨足系統生物學,靠著自我不斷精進,提高專業層次,點滴累積生物知識才能夠和李亨啓一拍即合。「2017年1月,我們在美國芝加哥大學台灣同學會春節聚餐上相識,可能因為同是台灣人所以很快就決定合作,李亨啓是諾貝爾獎得主Craig Mello門生,沒有深厚的生物底子很難搞懂他要什麼,此次跨國合作可說是天時地利加上人和。」

        吳謂勝指出,知識日新月異,現代生物學家多少都必要透過巨量分析獲得進一步結論,開發程式越顯重要,他把每個程式開發都當作孕育生命的過程,全心呵護。提到這次負責寫程式的學生黃偉哲,吳謂勝教授大力讚賞「他貢獻很大,從原本完全沒有經驗,經過自學克服許多難關。」

        溫文靦腆的黃偉哲做夢都沒想過自己的研究成果能登上《Science》,他笑說最感謝吳老師一路緊迫盯人,「老師很不一樣,一般研究生通常都是meeting的時候才會和指導教授見面,但是吳老師是每天、甚至假日都到實驗室關心我們的進度,一起討論。」面對細心又嚴格的吳老師雖然有過痛苦的日子,黃偉哲卻沒想過要放棄,他說很幸運能有這段很好的訓練,覺得很有成就感。

        piScan這個網頁工具還未公開發表,就已經備受線蟲生物學家關注。吳謂勝指出,過去線蟲生物學家想使用報導基因(reporter gene)來進行研究,會因為被細胞內的防禦機制piRNA所辨認並受到抑制而無法表現,許多研究因此無法順利進行,這問題已經困擾線蟲生物學家20年。李亨啓找出線蟲中piRNA的結合法則,可以解釋為何外來核酸進到線蟲生殖細胞後通常表現都會受到抑制,進一步透過piScan這個工具,則可以更改螢光蛋白的核酸序列,以逃脫piRNA的結合而能成功表達螢光蛋白,讓線蟲生物學家可以輸入他們想在線蟲表達的核酸序列。也就是說,根據piRNA的結合法則,順利找出想要表現的序列並修正序列。「本來沒辦法成功表現的因此能順利表現,對生物學家而言將可說是震撼性突破。」

        根據《科學月刊》第555期提到,「以線蟲為主題的研究論文就有超過上萬篇,甚至還有6位科學家,因線蟲研究而獲頒諾貝爾獎。」足見線蟲生物學家者眾,吳謂勝的開發成果,有助於揭開更多線蟲基因的奧秘。