85折優惠券.

跟著城市嚮導「老臺北胃」，用味道認識臺北

很多朋友來臺北，
都會問我同一個問題：
「臺北小吃那麼多，到底該從哪裡開始吃？」
夜市裡攤位一字排開、老店藏在巷弄轉角，
看起來都很有名，卻又怕吃錯、踩雷，
結果行程走完，反而沒真正記住臺北的味道。
我常被朋友笑說是「老臺北胃」。
不是因為特別會吃，而是因為在這座城市待久了，
知道哪些味道是陪著臺北人成長的日常。
這篇文章，就是我整理的一份清單。
如果你第一次來臺北，
我會帶你從這 10 樣最具代表性的臺北小吃開始，
不追一時爆紅、不走浮誇路線，
而是讓你吃完後能真正理解
原來，這就是臺灣的小吃文化。
跟著老臺北胃走，
用最簡單的方式，
把臺北的味道，一樣一樣記在心裡。

我怎麼選出這 10 大臺北小吃？

在臺北，
你隨便走進一條夜市或老街，
都可以輕易列出 30 種以上的小吃。
所以這份清單，
不是「臺北最好吃」的排名，
 而是我站在「第一次來臺北的旅客」角度，
做的推薦。
身為一個被朋友稱作「老臺北胃」的人，
我選這 10 樣小吃時，心裡一直放著幾個原則。

一吃就知道：這就是臺灣味

燒烤、火鍋很好吃，
但換個城市、換個國家，也吃得到。
我挑的，是那種
只要一入口，就會讓人聯想到的臺灣味。
 不需要解釋太多，舌頭就能懂。

不只是好吃，而是有「臺北日常感」

臺北的小吃迷人，
不只在味道，
而在它融入生活的方式。
我在意的是：

1. 會不會出現在早餐、宵夜、下班後
   
2. 有沒有陪伴這座城市很久的記憶
   

吃完之後，你會記得臺北

最後一個標準很簡單。
如果你回到家，
還會突然想起某個味道、某碗熱湯、某個攤位的香氣
那它就值得被放進這份清單裡。

接下來的 10 樣臺北小吃，
就是我會親自帶朋友去吃的在地美食。
不趕行程、不拚數量，
而是一口一口，
慢慢認識臺北。

第 1 家：饌堂－黑金滷肉飯（雙連店）｜一碗就懂臺灣人的日常

如果只能用一道料理，
 來解釋臺灣人的日常飲食，
 那我一定會先帶你吃滷肉飯。
在臺北，滷肉飯不是什麼特別的節慶料理，
 而是從早餐、午餐到宵夜，
 默默陪著很多人長大的味道。
而在眾多滷肉飯之中，
饌堂－黑金滷肉飯（雙連店），
 我很常帶第一次來臺北的朋友造訪的一家。

為什麼第一站，我會選饌堂？
饌堂的滷肉飯，走的是**「黑金系」路線**。
滷汁顏色深、香氣厚，
卻不死鹹、不油膩。
滷肉切得細緻，
肥肉入口即化，搭配熱騰騰的白飯，
每一口都是很完整、很臺灣的味道。
對第一次吃滷肉飯的旅客來說，
這種風味夠經典、也夠穩定，
不需要太多心理準備，就能理解為什麼臺灣人這麼愛它。

不只是好吃，而是「現在的臺北感」
饌堂並不是那種躲在深巷裡的老攤，
空間乾淨、節奏俐落，
卻沒有失去滷肉飯該有的靈魂。
這也是我會推薦給旅客的原因之一：
它保留了臺灣小吃的核心味道，
同時也讓第一次來臺北的人，
吃得安心、坐得舒服。

老臺北胃的帶路小提醒
如果是第一次來：

1. 一定要點招牌黑金滷肉飯
   
2. 可以加一顆滷蛋，風味會更完整
   
3. 搭配簡單的小菜，就很有臺灣家常感
   

這不是那種吃完會驚呼「哇！」的料理，
而是會讓你在幾口之後，
慢慢理解
原來，臺灣人的日常，就是這樣被一碗飯照顧著。

地址：103臺北市大同區雙連街55號1樓

電話：0225501379

菜單：https://bio.site/ZhuanTang

第 2 家：富宏牛肉麵｜臺北深夜也醒著的一碗熱湯

如果說滷肉飯代表的是臺灣人的日常，
 那牛肉麵，
 就是很多臺北人心中最有份量的一餐。
而在臺北提到牛肉麵，
 富宏牛肉麵，
 幾乎是夜貓族、加班族、外地旅客一定會被帶去的一站。

為什麼老臺北胃會帶你來吃富宏？
富宏最讓人印象深刻的，
不是華麗裝潢，
而是那鍋永遠冒著熱氣的紅燒湯頭。
湯色濃而不混，
帶著牛骨與醬香慢慢熬出的厚度，
喝起來溫潤、不刺激，
卻會在嘴裡留下很深的記憶點。
牛肉給得大方，
燉到軟嫩卻不鬆散，
搭配彈性十足的麵條，
每一口都很直接、很臺北。

不分時間，任何時候都適合的一碗麵
富宏牛肉麵最迷人的地方，
在於它陪伴了無數個臺北的夜晚。
不管是深夜下班、看完演唱會、
或是剛抵達臺北、還沒適應時差，
這裡總有一碗熱湯在等你。
對旅客來說，
這種不用算時間、不用擔心打烊的安心感，
本身就是一種臺北特色。

老臺北胃的帶路小提醒
第一次來富宏，我會這樣點：

1. 紅燒牛肉麵是首選
   
2. 如果想吃得更過癮，可以加點牛筋或牛肚
   
3. 湯先喝一口原味，再視情況調整辣度
   

這不是精緻料理，
卻是一碗能在任何時刻撐住你的牛肉麵。
在臺北，
很多夜晚，
就是靠這樣一碗熱湯走過來的。

地址：108臺北市萬華區洛陽街67號

電話：0223713028

菜單：https://www.facebook.com/pages/富宏牛肉麵-原建宏牛肉麵/

第 3 家：士林夜市・吉彖皮蛋涼麵｜臺北夏天最有記憶點的一口清爽

如果你在夏天來到臺北，
 一定會很快發現一件事
 這座城市，真的很熱。
也正因為這樣，
 臺北的小吃世界裡，
 才會出現像「涼麵」這樣的存在。
而在士林夜市，
 吉彖皮蛋涼麵，
 就是我很常帶旅客來吃的一家。

為什麼在夜市，我會帶你吃涼麵？
很多人對夜市的印象，
都是炸物、熱湯、重口味。
但真正的臺北夜市，
其實也很懂得照顧人的胃。
吉彖的涼麵，
冰涼的麵條拌上濃郁芝麻醬，
再加上切得細緻的皮蛋，
入口的第一瞬間，
就是一種「被降溫」的感覺。
那種清爽，
不是沒味道，
而是在濃香與清涼之間取得剛剛好的平衡。

皮蛋，是靈魂，也是臺灣味的關鍵
對很多外國旅客來說，
皮蛋是既好奇、又有點猶豫的存在。
但我常說，
如果要嘗試皮蛋，
涼麵是一個非常溫柔的起點。
芝麻醬的香氣會先接住味蕾，
皮蛋的風味則在後段慢慢出現，
不衝、不嗆，
反而多了一層深度。
很多人吃完後，
都會露出那種「原來是這樣啊」的表情。

老臺北胃的帶路小提醒
第一次點吉彖皮蛋涼麵，我會建議：

1. 一定要選皮蛋款，才吃得到特色
   
2. 醬料先拌勻，再吃，風味會更完整
   
3. 如果天氣真的很熱，這一碗會救你一整晚
   

這不是華麗的小吃，
卻非常臺北。
在悶熱的夜晚，
站在夜市人潮裡，
吃著一碗涼麵，
你會突然明白——

原來臺北的小吃，連氣候都一起考慮進去了。

地址：111臺北市士林區基河路114號

電話：0981014155

菜單：https://www.facebook.com/profile.php?id=100064238763064

第 4 家：胖老闆誠意肉粥｜臺北人深夜最踏實的一碗粥

如果你問我，
 臺北人在深夜、下班後，
 最容易感到被安慰的食物是什麼——
 我會毫不猶豫地說：肉粥。
而提到肉粥，
 胖老闆誠意肉粥，
 就是很多老臺北人口中的那一味。

為什麼這一碗粥，會被叫做「誠意」？
胖老闆的肉粥，看起來很簡單。
白粥、肉燥、配菜，
沒有華麗擺盤，也沒有複雜作法。
但真正坐下來吃，你會發現：
這碗粥，不敷衍任何一個細節。
粥體滑順、不稀薄，
肉燥香而不膩，
搭配各式家常小菜，
一口一口吃下去，
很自然就會放慢速度。
這種味道，
不是要你驚艷，
而是要你安心。

這不是觀光小吃，而是臺北人的生活片段
胖老闆誠意肉粥，
最迷人的地方，
就是它的客人。
你會看到：

1. 剛下班的上班族
   
2. 熬夜後來吃一碗熱粥的人
   
3. 熟門熟路、點菜不用看菜單的老客人
   

這些畫面，
比任何裝潢都更能說明這家店在臺北的位置。
對旅客來說，
這是一個走進臺北人日常的入口。

老臺北胃的帶路小提醒
第一次來吃，我會這樣建議：

1. 肉粥一定要點，這是主角
   
2. 配幾樣小菜一起吃，才有完整體驗
   
3. 不用急，慢慢吃，這碗粥就是要你放鬆
   

這不是為了拍照而存在的小吃，
而是那種
**會讓人記得「那天晚上，我在臺北吃了一碗很溫暖的粥」**的味道。

地址：10491臺北市中山區長春路89-3號

電話：0913806139

菜單：https://lin.ee/xxbYZyS

第 5 家：圓環邊蚵仔煎｜夜市裡最不能缺席的臺灣經典

如果要選一道
 最常出現在旅客記憶裡的臺灣小吃，
 蚵仔煎一定排得上前幾名。
而在臺北，
 圓環邊蚵仔煎，
 就是那種很多臺北人從小吃到大的存在。

為什麼蚵仔煎，這麼能代表臺灣？
蚵仔煎的魅力，
不在於精緻，
而在於它把幾種看似簡單的食材，
煎成了一種獨特的口感。
新鮮蚵仔的海味、
雞蛋的香氣、
地瓜粉形成的滑嫩外皮，
最後再淋上甜中帶鹹的醬汁，
一口下去，
就是夜市的完整畫面。
這種味道，
很難在其他國家找到替代品。

圓環邊，吃的是記憶感
圓環邊蚵仔煎，
沒有多餘的包裝，
也不刻意迎合潮流。
它留下來的原因很簡單
味道夠穩、節奏夠快、
讓人一吃就知道「對，就是這個」。
對旅客來說，
這是一家
不需要研究、不需要比較，就能安心點蚵仔煎的地方。

老臺北胃的帶路小提醒
第一次吃蚵仔煎，我會這樣建議：

1. 趁熱吃，口感最好
   
2. 不用急著加辣，先吃原味
   
3. 醬汁是靈魂，別急著把它拌掉
   

蚵仔煎不是細嚼慢嚥的料理，
它屬於人聲鼎沸、鍋鏟作響的夜市時刻。
站在人群裡，
吃著一盤熱騰騰的蚵仔煎，
你會很清楚地感受到
這，就是臺北的夜晚。

地址：103臺北市大同區寧夏路46號

電話：0225580198

菜單：https://oystera.com.tw/menu

第 6 家：阿淑清蒸肉圓｜第一次吃肉圓，就該從這裡開始

說到臺灣小吃，
 很多人腦中一定會出現「肉圓」兩個字。
但真正吃過之後才會發現，
 肉圓，從來不只有一種樣子。
在臺北，
 阿淑清蒸肉圓，
 就是我很常拿來介紹「清蒸派肉圓」的一家。

清蒸肉圓，和你想像的不一樣
不少旅客對肉圓的第一印象，
來自油炸版本，
外皮厚、口感重。
而阿淑的清蒸肉圓，
完全是另一個方向。
外皮晶瑩、滑嫩，
帶著自然的彈性，
不油、不膩，
一入口反而顯得清爽。
內餡扎實，
豬肉香氣清楚，
搭配特製醬汁，
味道層次簡單卻很乾淨。

為什麼我會推薦給第一次來臺北的旅客？
因為這顆肉圓，
不需要適應期。
它不刺激、不厚重，
即使是第一次嘗試臺灣小吃的人，
也能輕鬆接受。
對旅客來說，
這是一顆
「吃得懂、也記得住」的肉圓。

老臺北胃的帶路小提醒
第一次來阿淑，我會這樣吃：

1. 直接點一顆清蒸肉圓，吃原味
   
2. 醬汁先別全部拌開，邊吃邊調整
   
3. 放慢速度，感受外皮的口感變化
   

這不是夜市裡熱鬧喧囂的料理，
而是那種
安靜地展現臺灣小吃功夫的味道。
當你吃完這顆肉圓，
會更明白一件事
臺灣小吃的魅力，
往往藏在這些細節裡。

地址：242新北市新莊區復興路一段141號

電話：0229975505

第 7 家：胡記米粉湯｜一碗最貼近臺北早晨的味道

如果說前面幾樣小吃，
 是臺北的熱鬧與記憶，
 那麼米粉湯，
 就是這座城市最真實的日常。
而在臺北，
 胡記米粉湯，
 是很多人從小吃到大的存在。

為什麼米粉湯，這麼「臺北」？
米粉湯不是重口味料理，
它靠的不是刺激，
而是一碗清澈卻有深度的湯。
胡記的湯頭，
用豬骨慢慢熬出香氣，
喝起來清爽、不油，
卻能在喉嚨留下溫度。
米粉細軟，
吸附湯汁後入口順滑，
簡單到不能再簡單，
卻正是臺北人習以為常的早晨風景。

配菜，才是這一碗的靈魂延伸
在胡記吃米粉湯，
主角雖然是湯，
但真正讓人滿足的，
往往是那些小菜。
紅燒肉、豬內臟、燙青菜，
隨意點上幾樣，
湯一口、菜一口，
就是很多臺北人記憶中的早餐組合。
對旅客來說，
這是一種
不需要解釋，就能融入的臺北生活感。

老臺北胃的帶路小提醒
第一次來胡記，我會這樣建議：

1. 一定要點米粉湯，湯先喝
   
2. 再配 1～2 樣小菜，體驗會完整很多
   
3. 這一餐適合慢慢吃，不用趕
   

這不是為了觀光而存在的小吃，
而是一碗
每天準時出現在臺北人生活裡的湯。
當你坐在店裡，
聽著湯勺碰撞的聲音，
你會突然感覺到——
原來，臺北的早晨，
就是從這樣一碗米粉湯開始的。

地址：106臺北市大安區大安路一段9號1樓

電話：0227212120

第 8 家：藍家割包｜一口咬下的臺灣街頭記憶

如果要選一道
 外國旅客一看到就會好奇、吃完又會記住的小吃，
 割包，一定在名單裡。
而在臺北，
 藍家割包，
 就是我很放心帶旅客來認識這道經典的一站。

割包，為什麼被叫做「臺灣漢堡」？
割包的結構其實很簡單：
鬆軟的白饅頭、
燉得入味的滷五花肉、
酸菜、花生粉、香菜。
但真正迷人的，
是這些元素組合在一起時，
形成的層次感。
肉香、甜味、鹹味、清爽度，
在一口之間同時出現，
沒有誰搶戲，
卻彼此剛好。
這種平衡感，
正是臺灣小吃很迷人的地方。

藍家割包不是走浮誇路線，
它給人的感覺很直接
就是你期待中的割包樣子。
饅頭柔軟不乾，
五花肉肥瘦比例恰到好處，
入口即化卻不膩口，
花生粉的甜香收尾，
讓整體味道非常完整。
對第一次吃割包的旅客來說，
這是一個
不會出錯、也很容易愛上的版本。

老臺北胃的帶路小提醒
第一次吃藍家割包，我會這樣建議：

1. 直接點招牌割包，不要改配料
   
2. 如果有香菜，建議保留，味道會更完整
   
3. 趁熱吃，饅頭口感最好
   

割包不是精緻料理，
卻非常有記憶點。
站在街頭，
拿著一顆熱騰騰的割包，
邊走邊吃，
你會很清楚地感受到
這一口，就是臺灣的街頭生活。

地址：100臺北市中正區羅斯福路三段316巷8弄3號

電話：0223682060

菜單：https://instagram.com/lan_jia_gua_bao?utm_medium=copy_link

第 9 家：御品元冰火湯圓｜臺北夜晚最溫柔的一碗甜

吃了一整天的臺北小吃，
 到了這個時候，
 胃其實已經差不多滿了。
但只要天氣一涼，
 或夜色慢慢降下來，
 你還是會想找一碗——
 不是為了吃飽，而是為了舒服的甜點。
這時候，我通常會帶你來 御品元冰火湯圓。

為什麼叫「冰火」？這碗湯圓的關鍵就在這裡
御品元最有特色的地方，
就在於它的「冰火交錯」。
熱騰騰的湯圓，
外皮軟糯、內餡濃香，
搭配冰涼清甜的桂花蜜湯，
一口下去，
溫度在嘴裡交替出現。
不是衝突，
而是一種很細膩的平衡。
這樣的吃法，
也正是臺灣甜點很擅長的地方——
不張揚，但很有記憶點。

這是一碗，會讓人慢下來的甜點
和夜市裡熱鬧的甜品不同，
御品元的冰火湯圓，
更像是一個讓人停下腳步的存在。
你會發現，
坐在這裡吃湯圓的人，
說話聲都會不自覺地變小。
對旅客來說，
這不只是吃甜點，
而是一個
把白天的熱鬧慢慢收進回憶裡的時刻。

老臺北胃的帶路小提醒
第一次吃御品元，我會這樣建議：

1. 點招牌冰火湯圓，體驗完整特色
   
2. 先單吃湯圓，再搭配湯一起吃
   
3. 放慢速度，這一碗不適合趕時間
   

這不是為了拍照而存在的甜點，
而是一碗
會讓你記得「那天晚上在臺北，很舒服」的湯圓。

地址：106臺北市大安區通化街39巷50弄31號

電話：0955861816

菜單：https://instagram.com/lan_jia_gua_bao

第 10 家：頃刻間綠豆沙牛奶專賣店｜把臺北的味道，留在最後一口清甜

走到這一站，
 其實已經不需要再吃什麼大份量的東西了。
這時候，
 最適合的，
 是一杯不吵鬧、不張揚，
 卻會默默留在記憶裡的飲品。
頃刻間綠豆沙牛奶，
 就是我很常用來替一天畫下句點的選擇。

綠豆沙牛奶，為什麼這麼「臺灣」？
在臺灣，
飲料不只是解渴，
而是一種生活節奏。
綠豆沙牛奶看起來簡單，
但真正好喝的版本，
靠的是火候、比例，
還有耐心。
頃刻間的綠豆沙，
口感細緻、不粗顆，
甜度自然、不膩口，
牛奶的加入，
讓整杯變得柔順而溫和。
這不是衝擊味蕾的飲料，
而是一種
喝完之後，會覺得剛剛那一刻很舒服的甜。

為什麼我會用它當作最後一站？
因為它很臺北。
你可以外帶，
邊走邊喝；
也可以站在店門口，
慢慢把杯子喝空。
沒有儀式感，
卻很真實。
對旅客來說，
這杯綠豆沙牛奶，
就像是把今天吃過的所有味道，
溫柔地整理好，
帶走。

老臺北胃的帶路小提醒
第一次喝頃刻間，我會這樣建議：

1. 直接點招牌綠豆沙牛奶
   
2. 正常甜就很剛好，不用特別調整
   
3. 找個角落慢慢喝，別急著趕路
   

這一杯，
不會讓你驚呼，
卻會在回程的路上，
突然想起來。
原來，臺北的味道，是這樣結束一天的。

地址：111臺北市士林區小北街1號

電話：0228818619

菜單：https://instagram.com/chill_out_moment?igshid=YmMyMTA2M2Y=

如果只有 3 天的自助旅行在臺北，怎麼吃這 10 家？

第一次來臺北，
時間有限、胃容量也有限，
與其每一家都趕，不如照著節奏吃。
這份 3 天小吃路線，
是老臺北胃會帶朋友實際走的版本：
不爆走、不硬塞，
讓你每天都吃得剛剛好。

臺北 3 天小吃推薦行程表（老臺北胃版本）

雖然每個小吃的地點都有一點距離，但是你也知道，好吃的小吃，是值得你花一點時間前往品嘗
老臺北胃的小提醒

1. 不需要每一家都點到最滿
   
2. 留一點餘裕，才會想再回來
   
3. 臺北小吃的魅力，不在於吃多少，而在於記住了什麼味道
   

當你照著這 3 天走完，
你會發現，
臺北不是靠一兩道名菜被記住的，
而是靠這些看似日常、卻很真實的小吃。
下次再來，老臺北胃再帶你吃更深的那一輪。

老臺北胃帶路｜這 10 口，就是我心中的臺北

寫到這裡，
 其實已經不是在推薦哪一家小吃了。
而是在回頭看，
 這座城市，是怎麼用食物陪著人生活的。
滷肉飯、牛肉麵、肉粥、米粉湯，
 不是為了成為觀光名單而存在，
 而是每天默默出現在臺北人的日子裡。
夜市裡的蚵仔煎、涼麵、割包，
 熱鬧、吵雜、節奏很快，
 卻也正是臺北最真實的樣子。
而最後那碗湯圓、那杯綠豆沙牛奶，
 則是在一天結束時，
 替味蕾留下一個溫柔的句點。

如果你問我，
「這 10 家是不是臺北最好吃的小吃？」
我會說，
它們不一定是排行榜第一名，
卻是我真的會帶朋友去吃的版本。
因為它們吃得到：

1. 臺北人的日常
   
2. 巷弄裡的熟悉感
   
3. 不需要解釋，就能被理解的味道
   

如果你是第一次來臺北，
跟著這份清單走，
你不一定會吃得最飽，
但你一定會記得——
臺北，是什麼味道。
而如果有一天，
你又再回到這座城市，
走進熟悉的街口、
看到冒著熱氣的小攤，
你也會開始懂得，
為什麼老臺北胃，
總是記得這些看似平凡的滋味。
因為，真正留在心裡的，
從來不是吃過多少，
而是哪一口，讓你想起臺北。

士林夜市－吉彖皮蛋涼麵推薦嗎？

走完這 10 家，

你可能會發現一件事御品元冰火湯圓一定要點嗎？

臺北的小吃，其實不急著被你記住。

它們就安靜地存在在街角、夜市、轉彎處，藍家割包怎麼點比較好？

等你有一天，再回到這座城市。富宏牛肉麵當正餐適合嗎？

如果你是第一次來臺北，頃刻間綠豆沙牛奶專賣店會不會膩？

希望這份「老臺北胃帶路」的清單，

能幫你少一點猶豫、多一點安心。

不用擔心踩雷，御品元冰火湯圓排隊值得嗎？

也不用為了排行而奔波，富宏牛肉麵吃過會想再來嗎？

只要照著節奏走，

你就會吃到屬於自己的臺北味道。

而如果你已經來過臺北，

那更希望這篇文章，胖老闆誠意肉粥男生會吃得飽嗎？

能帶你走進那些

你可能錯過、卻一直都在的日常小吃。

因為真正迷人的旅行，

從來不是把清單全部打勾，

而是某一天，

你突然想起那碗飯、那口湯、那杯甜，富宏牛肉麵好吃嗎？

然後在心裡對自己說一句：圓環邊蚵仔煎吃起來順口嗎？

「下次再去臺北，還想再吃一次。」

把這篇文章存起來、分享給一起旅行的人，

或是在規劃行程時，再回來看看。

讓味道，成為你認識臺北的方式。

下一次來臺北，

別急著走遠。

老臺北胃，藍家割包不加辣好吃嗎？

會一直在這些地方，

等你再回來。

Light microscope images of E. coli cells in transmitted light (left) and reflected light that picks up the red fluorescence of a dye staining the cells’ DNA (right). In normal cells (upper panel), the DNA is spread throughout the cells. But in cells expressing the aberrant plant protein identified in this study (bottom panel) all the DNA within each cell has collapsed into a dense mass. DNA condensation also occurs after bacteria have been treated with aminoglycoside antibiotics. Credit: Brookhaven National Laboratory Discovery of an aberrant protein that kills bacterial cells could help unravel the mechanism of certain antibiotics and point the way to new drugs. An aberrant protein that’s deadly to bacteria has been discovered by biologists from the U.S. Department of Energy’s Brookhaven National Laboratory and their collaborators. In a paper that will be published today (April 29, 2022) in the journal PLOS ONE, the scientists describe how this erroneously built protein mimics the action of aminoglycosides, a class of antibiotics. The newly found protein could serve as a model for scientists to decipher the specifics of those medications’ lethal impact on bacteria—and possibly point the way to future antibiotics. “Identifying new targets in bacteria and alternative strategies to control bacterial growth is going to become increasingly important,” said Brookhaven biologist Paul Freimuth, who led the research. Bacteria are becoming resistant to several routinely used antibiotics, and many scientists and clinicians are concerned about the possibility of large-scale epidemics caused by these antibiotic-resistant bacteria, he explained. “What we’ve discovered is a long way from becoming a drug, but the first step is to understand the mechanism,” Freimuth said. “We’ve identified a single protein that mimics the effect of a complex mixture of aberrant proteins made when bacteria are treated with aminoglycosides. That gives us a way to study the mechanism that kills the bacterial cells. Then maybe a new family of inhibitors could be developed to do the same thing.” Following an Interesting Branch The Brookhaven scientists, who normally focus on energy-related research, weren’t thinking about human health when they began this project. They were using E. coli bacteria to study genes involved in building plant cell walls. That research could help scientists learn how to convert plant matter (biomass) into biofuels more efficiently. Brookhaven Lab biologist Paul Freimuth and co-author Feiyue Teng, a scientist in Brookhaven Lab’s Center for Functional Nanomaterials (CFN), at the light microscope used to image bacteria in this study. Credit: Brookhaven National Laboratory But when they turned on expression of one particular plant gene, enabling the bacteria to make the protein, the cells stopped growing immediately. “This protein had an acutely toxic effect on the cells. All the cells died within minutes of turning on expression of this gene,” Freimuth said. Understanding the basis for this rapid inhibition of cell growth made an ideal research project for summer interns working in Freimuth’s lab. “Interns could run experiments and see the effects within a single day,” he said. And maybe they could help figure out why a plant protein would cause such dramatic damage. Misread Code, Unfolded Proteins “That’s when it really started to get interesting,” Freimuth said. The group discovered that the toxic factor wasn’t a plant protein at all. It was a strand of amino acids, the building blocks of proteins, that made no sense. This nonsense strand had been churned out by mistake when the bacteria’s ribosomes (the cells’ protein-making machinery) translated the letters that make up the genetic code “out of phase.” Instead of reading the code in chunks of three letters that code for a particular amino acid, the ribosome read only the second two letters of one chunk plus the first letter of the next triplet. That resulted in putting the wrong amino acids in place. “It would be like reading a sentence starting at the middle of each word and joining it to the first half of the next word to produce a string of gibberish,” Freimuth said. The gibberish protein reminded Freimuth of a class of antibiotics called aminoglycosides. These antibiotics force ribosomes to make similar “phasing” mistakes and other sorts of errors when building proteins. The result: all the bacteria’s ribosomes make gibberish proteins. “If a bacterial cell has 50,000 ribosomes, each one churning out a different aberrant protein, does the toxic effect result from one specific aberrant protein or from a combination of many? This question emerged decades ago and had never been resolved,” Freimuth said. According to the current findings, just a single aberrant protein can be sufficient for the toxic effect. That wouldn’t be too farfetched. Nonsense strands of amino acids can’t fold up properly to become fully functional. Although misfolded proteins get produced in all cells by chance errors, they usually are detected and eliminated completely by “quality control” machinery in healthy cells. Breakdown of quality control systems could make aberrant proteins accumulate, causing disease. Messed-Up Quality Control The next step was to find out if the aberrant plant protein could activate the bacterial cells’ quality control system—or somehow block that system from working. Freimuth and his team found that the aberrant plant protein indeed activated the initial step in protein quality control, but that later stages of the process directly required for degradation of aberrant proteins were blocked. They also discovered that the difference between cell life and death was dependent on the rate at which the aberrant protein was produced. “When cells contained many copies of the gene coding for the aberrant plant protein, the quality control machinery detected the protein but was unable to fully degrade it,” Freimuth said. “When we reduced the number of gene copies, however, the quality control machinery was able to eliminate the toxic protein and the cells survived.” The same thing happens, he noted, in cells treated with sublethal doses of aminoglycoside antibiotics. “The quality control response was strongly activated, but the cells still were able to continue to grow,” he said. Model for Mechanism These experiments indicated that the single aberrant plant protein killed cells by the same mechanism as the complex mixture of aberrant proteins induced by aminoglycoside antibiotics. But the precise mechanism of cell death is still a mystery. “The good news is that now we have a single protein, with a known amino acid sequence, that we can use as a model to explore that mechanism,” Freimuth said. Scientists know that cells treated with the antibiotics become leaky, allowing toxic levels of things like salts to seep in. One hypothesis is that the misfolded proteins might form new channels in cellular membranes, or alternatively jam open the gates of existing channels, allowing diffusion of salts and other toxic substances across the cell membrane. “A next step would be to determine structures of our protein in complex with membrane channels, to investigate how the protein might inhibit normal channel function,” Freimuth said. That would help advance understanding of how the aberrant proteins induced by aminoglycoside antibiotics kill bacterial cells—and could inform the design of new drugs to trigger the same or similar effects. Reference: “A polypeptide model for toxic aberrant proteins induced by aminoglycoside antibiotics” by Mangala Tawde, Abdelaziz Bior, Michael Feiss, Feiyue Teng and Paul Freimuth, 29 April 2022, PLOS ONE. DOI: 10.1371/journal.pone.0258794 This work was supported by a Laboratory Directed Research and Development award from Brookhaven Lab and in part by the DOE Office of Science, Office of Workforce Development for Teachers and Scientists (WDTS) under the Visiting Faculty Program (VFP). Additional funding from the National Science Foundation (NSF) supported students participating in internships under NSF’s Science, Technology, Engineering, and Mathematics Talent Expansion Program (STEP) and the Louis Stokes Alliances for Minority Participation (LSAMP) program.

Dynein intermediate chain structure showing folded WD repeat domain in the center (blue) and disordered N-terminal domain (orange). Illustrated on the left are multiple models of open and closed structures of the disordered domain (grey) bound to light chains (yellow, red, and orange blobs). Credit: Elisar Barbar, OSU College of Science. OSU research revealed how dynein’s intermediate chain regulates cellular transport, offering insights into neurodegenerative diseases. Scientists at Oregon State University have made a key advancement in understanding neurodegenerative diseases by utilizing various biophysical techniques to gain insight into a motor protein that plays a crucial role in many disorders. The study, which was published in the journal eLife, represents a significant step forward in the effort to improve care for the millions of people worldwide who are affected by conditions such as Alzheimer’s disease, ALS, Parkinson’s disease, and multiple sclerosis. Neurodegenerative diseases occur when nerve cells in the brain and spinal cord, known as neurons, break down, function abnormally, and eventually die. As neurons deteriorate, patients typically experience a range of gradually worsening neurological symptoms that can progress to debilitation and, in many cases, death. According to the Harvard NeuroDiscovery Center, 5 million people in the United States have Alzheimer’s disease and 1 million have Parkinson’s. There are also 400,000 MS patients and 30,000 have ALS, a disease that reached the public’s consciousness when baseball star Lou Gehrig was diagnosed with it in 1939. Neurodegenerative conditions onset primarily in mid- to late-life, meaning the incidence is expected to rise as the U.S. population ages. Demographic data suggest that without new interventions more than 12 million Americans will be affected by neurodegenerative diseases by 2050. Dynein: The Cellular Motor Protein Elisar Barbar, head of the Department of Biochemistry and Biophysics in the OSU College of Science, and Kayla Jara, program coordinator for Oregon State’s genetic code expansion center, GCE4All, led a deep dive into dynein, one of the two types of motor proteins within cells; the other type is kinesin. Motor proteins are tiny molecular machines that animal and fungi cells use to convert chemical energy into mechanical work. They are miniature “vehicles” traversing a cell via a network of tracks referred to as the cytoskeleton, hauling a cellular payload and generating forces to aid in many vital processes and functions. Investigating Dynein’s Intermediate Chain “Dynein is responsible for the transport of cargo that controls cell proliferation and differentiation in the nervous system in the immediate aftermath of injury and during regeneration,” Jara said. “Neurodegenerative diseases arise as a consequence of mutations in the genes that produce components of the dynein motor and impair transport machinery in the axon.” Nerve cells can be very long and heavily dependent on motor proteins to ensure the transport of material between the cell body and the tip of the axon, she said. A cable that extends from the main part of the cell, the axon transmits electrical impulses from one neuron to other neurons. “Just as freeways connect towns and cities, inside our cells lie an array of roads called microtubules that the motor proteins use to shuttle their loads,” Barbar said. “Dynein is responsible for carrying cargo in one direction, and about 40 proteins of the kinesin type haul in the opposite direction. That suggests there are intricate methods of regulation between the many subunit proteins that together make up dynein.” In this study, Barbar and Jara, a doctoral student during the research, collaborated with scientists from Oregon State and Lewis & Clark College for a close look at one of those subunits: the intermediate chain, or IC, which acts as a binder for other subunits as well as for two non-dynein proteins, p150Glued and NudE. Unveiling IC’s Binding Mechanism “These binding interactions all take place in the first half of IC, which has escaped study by many structural techniques because it doesn’t fold into a specific structure,” Barbar said. “We wanted to find out how the binding of the subunits regulates IC interactions with p150Glued and NudE. This question has gone unanswered because of the difficulty in studying unstructured protein complexes of this size. But p150Glued and NudE bind to the same region of IC, and those proteins are involved in different dynein functions, so there must be a mechanism to select between the two.” Studying proteins from a fungus, Chaetomium thermophilum, the scientists learned what that mechanism is: IC’s ability to fold back on itself and affect the p150Glued/NudE binding site. Due to the challenge of conducting research into non-structured proteins, many biophysical techniques were used in combination, Jara said, which resulted in a blueprint for how to study other, similar protein complexes. “Dynein is the molecular motor responsible for the transport of misfolded proteins so they can be broken down, meaning it is crucially involved in the appearance and clearance of proteins that are a hallmark of neurodegenerative diseases,” Jara added. “In particular, dynein malfunction is an early feature in disorders such as ALS and Alzheimer’s. Knowledge about the dynein structure and how it works will contribute to our understanding and treatment of these disorders.” Reference: “Multivalency, autoinhibition, and protein disorder in the regulation of interactions of dynein intermediate chain with dynactin and the nuclear distribution protein” by Kayla A Jara, Nikolaus M Loening, Patrick N Reardon, Zhen Yu, Prajna Woonnimani, Coban Brooks, Cat H Vesely and Elisar J Barbar, 23 November 2022, eLife. DOI: 10.7554/eLife.80217 The study was funded by the National Science Foundation, the National Institutes of Health, and the M.J. Murdock Charitable Trust.

Intestine cross-section showing its characteristic folded structure. Credit: Amy Engevik An international team led by Xavier Trepat at IBEC, with support from “La Caixa Foundation, measures the cellular forces in mini-intestines grown in the laboratory, deciphering how the inner wall of this vital organ folds and moves. The study, published in Nature Cell Biology, opens the doors to a better understanding of the bases of diseases such as celiac disease or cancer, and to the ability to find solutions for gut diseases through the development of new therapies. The human intestine is made up of more than 40 square meters (430 square feet) of tissue, with a multitude of folds on its internal surface that resemble valleys and mountain peaks in order to increase the absorption of nutrients. The intestine also has the unique characteristic of being in a continuous state of self-renewal. This means that approximately every 5 days all the cells of its inner walls are renewed to guarantee correct intestinal function. Until now, scientists knew that this renewal could take place thanks to stem cells, which are protected in the so-called intestinal crypts, and which give rise to new differentiated cells. However, the process that leads to the concave shape of the crypts and the migration of new cells towards the intestinal peaks was unknown. Now, an international team led by Xavier Trepat, ICREA Research Professor and Group Leader at IBEC, in collaboration with the IRB, researchers from the UB and UPC universities in Barcelona, and the Curie Institute of Paris, has deciphered the mechanisms leading the crypts to adopt and maintain their concave shape, and how the migration movement of the cells towards the peaks occurs, without the intestine losing its characteristic folded shape. The study, published in the prestigious journal Nature Cell Biology, has combined computer modeling, led by Marino Arroyo, professor at the UPC, researcher associated with IBEC and member of CIMNE, with experiments with intestinal organoids from mouse cells, and shows that this process is possible thanks to the mechanical forces exerted by the cells. An important part of this study has been supported by the “la Caixa” Foundation within the framework of the Caixa Research program. The entity has also awarded a scholarship to the first co-author, Gerardo Ceada, to carry out his PhD at IBEC. The forces determine and control the shape of the intestine and the movement of the cells Using mouse stem cells and bioengineering and mechanobiology techniques, researchers have developed mini-intestines, organoids that resemble the three-dimensional structure of peaks and valleys, recapitulating tissue functions in vivo. Using microscopy technologies developed by the same group, researchers carried out high-resolution experiments for the first time that have allowed them to obtain 3D maps showing the forces exerted by each cell. In addition, with this in vitro model, scientists have shown that the movement of new cells to the peak is also controlled by mechanical forces exerted by the cells themselves, specifically by the cytoskeleton, a network of filaments that determines and maintains cell shape. “Contrary to what was believed up until now, we have been able to determine that it is not the cells of the intestinal crypt that push the new ones up, but that it is the cells at the peak pulling the new ones up, akin to a mountaineer who helps another climber by pulling them up,” explains Gerardo Ceada from IBEC “With this system, we have discovered that the crypt is concave because the cells have more tension on their upper surface than on the bottom, which causes them to adopt a conical shape. When this occurs in several cells next to each other, the result is that the tissue folds, giving rise to a pattern of peaks and valleys,” adds Carlos Perez-Gonzalez, (IBEC and Curie Institute). The new mini-intestine model will allow further studies of diseases such as cancer, celiac disease or colitis to be conducted in reproducible and real conditions, in which there is an uncontrolled proliferation of stem cells or a destructuring of the folds. In addition, intestinal organoids can be manufactured with human cells and used for the development of new drugs or for the study of the intestinal microbiota. Reference: “Mechanical compartmentalization of the intestinal organoid enables crypt folding and collective cell migration” by Carlos Pérez-González, Gerardo Ceada, Francesco Greco, Marija Matejcic, Manuel Gómez-González, Natalia Castro, Anghara Menendez, Sohan Kale, Denis Krndija, Andrew G. Clark, Venkata Ram Gannavarapu, Adrián Álvarez-Varela, Pere Roca-Cusachs, Eduard Batlle, Danijela Matic Vignjevic, Marino Arroyo and Xavier Trepat, 21 June 2021, Nature Cell Biology. DOI: 10.1038/s41556-021-00699-6 X. Trepat is a member of the Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN). E. Batlle is a member of the Center for Biomedical Research in Cancer Network (CIBERONC). Both are research professors at the Catalan Institution for Research and Advanced Studies (ICREA). The Bioengineering Institute of Catalonia (IBEC) is a CERCA center, it has been twice named a “Severo Ochoa Center of Excellence” and has received the TECNIO seal as a technology developer and facilitator to companies. IBEC is a member of the Barcelona Institute of Science and Technology (BIST) and carries out multidisciplinary research of excellence on the boundary between engineering and life sciences to generate knowledge, integrating fields such as nanomedicine, biophysics, biotechnology, tissue engineering and information technology applications in the healthcare field. IBEC was created in 2005 by the Catalonian Government, the University of Barcelona (UB) and the Polytechnic University of Catalonia (UPC).

RE98915RGPOIOKJ

御品元冰火湯圓當宵夜適合嗎？ 》台北美食Top10｜選店困難症救星圓環邊蚵仔煎好吃嗎？ 》台北夜市美食10大美食推薦｜從燒肉到火鍋全攻略圓環邊蚵仔煎推薦嗎？ 》台北夜市美食必吃美食Top10｜高質感餐廳大集合