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 茶六燒肉堂節慶時段會不會太難訂位？》台中公益路美食Top10｜選店困難症救星 |
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身為一個熱愛美食、喜歡在城市裡挖掘驚喜的人，臺中公益路一直是我最常出沒的地方之一。這條路可說是「臺中人的美食戰場」，從精緻西餐到創意火鍋，從日式丼飯到義式早午餐，每走幾步，就會有完全不同的特色料理餐廳。 這次我特別花了一整個月，實際造訪了公益路上十間口碑不錯的餐廳。有的是網友熱推的打卡名店，也有隱藏在巷弄裡的小驚喜。我以環境氛圍、口味表現、價格CP值與再訪意願為基準，整理出這篇實測評比。希望能幫正在猶豫去哪裡吃飯的你，找到那一間「吃完會想再來」的餐廳。 評比標準與整理方向
這次我走訪的10家餐廳橫跨不同料理類型，從高質感牛排館到巷弄系早午餐，每一間都有自己獨特的風格。為了讓整體比較更客觀，我依照以下四大面向進行評比，並搭配實際用餐體驗來打分。
整體而言，我希望這份評比不只是「哪家好吃」，而是幫你在不同情境下（約會、家庭聚餐、朋友小聚、商業午餐）都能快速找到合適的選擇。畢竟，美食不只是味覺的滿足，更是一段段與朋友共享的生活記憶。 10間臺中公益路餐廳評比懶人包公益路向來是臺中人聚餐的首選地段，從火鍋、燒肉到中式料理與早午餐，每走幾步就有驚喜。以下是我實際造訪過的10間代表性餐廳清單，橫跨平價、創意、高級各路風格。
一頭牛日式燒肉｜炭香濃郁的和牛饗宴，約會聚餐首選
走在公益路上，很難不被 一頭牛日式燒肉 的木質外觀吸引。低調卻不失質感的門面，搭配昏黃燈光與暖色調的內裝，讓人一進門就感受到濃濃的日式職人氛圍。店內空間不大，但桌距規劃得宜，每桌皆設有獨立排煙設備，烤肉時完全不怕滿身油煙味。 餐點特色
一頭牛的靈魂，絕對是他們招牌的「三國和牛拼盤」。 用餐體驗整體節奏掌握得非常好。店員會在你剛想烤下一片肉時貼心遞上夾子、幫忙換烤網，讓人完全不用分心。整場用餐過程就像一場表演，從視覺、嗅覺到味覺都被滿足。 綜合評分
地址：408臺中市南屯區公益路二段162號電話：04-23206800 小結語一頭牛日式燒肉不僅是「吃肉的地方」，更像是一場五感盛宴。從進門那一刻到最後一道甜點，都能感受到他們對細節的用心。 TANG Zhan 湯棧｜文青系火鍋代表，麻香湯底與視覺美感並重
在公益路這條美食戰線上，TANG Zhan 湯棧 是讓人一眼就會想走進去的那一種。 餐點特色
湯棧最有名的當然是它的「麻香鍋」。 用餐體驗整體氛圍比一般火鍋店更有質感。 綜合評分
地址：408臺中市南屯區公益路二段248號電話：04-22580617 官網：https://www.facebook.com/TangZhan.tw/ 小結語TANG Zhan 湯棧 把傳統火鍋做出新的樣貌保留臺式鍋物的溫度，又結合現代風格與細節服務，讓吃鍋這件事變得更有品味。 如果你想找一間兼具「好吃、好拍、好放鬆」的火鍋店，湯棧會是公益路上最有風格的選擇之一。 NINI 尼尼臺中店｜明亮寬敞的義式早午餐天堂
如果說前兩間是肉食愛好者的天堂，那 NINI 尼尼臺中店 絕對是想放鬆、聊聊天的好地方。餐廳外觀以白色系與大片玻璃窗為主，陽光灑進室內，讓人一踏入就有種度假般的輕盈感。假日早午餐時段特別熱鬧，建議提早訂位。 餐點特色
NINI 的菜單融合義式與臺灣人口味，選擇多樣且份量十足。主打的 松露燉飯 濃郁卻不膩口，米芯保留微Q口感；而 香蒜海鮮義大利麵 則以新鮮白蝦、花枝與淡菜搭配微辣蒜香，口感層次豐富。 用餐體驗店內氣氛輕鬆不拘謹，無論是一個人帶電腦工作、或朋友聚餐，都能找到舒服角落。餐點上桌速度穩定，服務人員態度親切、補水與收盤都非常主動。整體節奏讓人覺得「時間變慢了」，很適合想遠離忙碌日常的人。 綜合評分
地址：40861臺中市南屯區公益路二段18號電話：04-23288498 小結語NINI 尼尼臺中店是一間能讓人放下手機、慢慢吃飯的餐廳。餐點不追求浮誇，而是以「剛剛好」的份量與風味，陪伴每個平凡午後。如果你在找一間能邊吃邊聊天、拍照也漂亮的早午餐店，NINI 會是你在公益路上最不費力的幸福選擇。 加分100%浜中特選昆布鍋物｜平價卻用心的湯頭系火鍋，家庭聚餐好選擇
在公益路這條高質感餐廳林立的戰場上，加分100%浜中特選昆布鍋物 走的是截然不同的路線。它沒有浮誇的裝潢、也沒有高價位的套餐，但靠著實在的湯頭與親切的服務，默默吸引許多回頭客。每到用餐時間，總能看到家庭或情侶三兩成群地圍著鍋邊聊天。 餐點特色
主打 北海道浜中昆布湯底，湯頭清澈卻不單薄，越煮越能喝出海藻與柴魚的自然香氣。 用餐體驗整體氛圍偏家庭取向，桌距寬敞、座位舒適，帶小孩來也不覺擁擠。店員態度親切，補湯、收盤都很勤快，給人一種「被照顧著」的安心感。 綜合評分
地址：403臺中市西區公益路288號電話：0910855180 小結語加分100%浜中特選昆布鍋物是一間「不浮誇、但會讓人想再訪」的火鍋店。它不追求豪華擺盤，而是用最簡單的湯頭與新鮮食材，傳遞出家常卻不平凡的溫度。 印月餐廳｜中式料理的藝術演繹，宴客與家庭聚會首選
說到臺中公益路的中式料理代表，印月餐廳 絕對是榜上有名。這間開業多年的餐廳以「中菜西吃」的概念聞名，把傳統中式料理以現代手法重新詮釋。從建築外觀到餐具擺設，每個細節都散發著低調的典雅氣息。 餐點特色
印月最令人印象深刻的是他們將傳統中菜融入創意手法。 用餐體驗服務方面完全對得起餐廳的高級定位。從入座、點餐到上菜節奏，都拿捏得恰如其分。每道菜都會有服務人員細心介紹食材與吃法，讓人感受到「被款待」的尊榮感。 綜合評分
地址：408臺中市南屯區公益路二段818號電話：0422511155 小結語印月餐廳是一間「不只吃飯，更像品味生活」的地方。 KoDō 和牛燒肉｜極致職人精神，專為儀式感與頂級味覺而生
若要形容 KoDō 和牛燒肉 的用餐體驗，一句話足以總結——「像在欣賞一場關於肉的表演」。 餐點特色
這裡主打 日本A5和牛冷藏肉，以「精切厚燒」的方式呈現。 用餐體驗KoDō 的最大特色是「儀式感」。 綜合評分
地址：403臺中市西區公益路260號電話：0423220312 官網：https://www.facebook.com/kodo2018/ 小結語KoDō 和牛燒肉不是日常餐廳，而是一場體驗。 永心鳳茶｜在茶香裡用餐的優雅時光，臺味早午餐的新詮釋
走進 永心鳳茶公益店，彷彿進入一間有氣質的茶館。 餐點特色
永心鳳茶的餐點結合中式靈魂與西式擺盤，無論是「炸雞腿飯」還是「紅玉紅茶拿鐵」，都能讓人感受到熟悉卻不平凡的味道。 用餐體驗店內服務人員態度溫和，對茶品介紹詳盡。上餐節奏剛好，不急不徐。 綜合評分
地址：40360臺中市西區公益路68號三樓(勤美誠品)電話：0423221118 小結語永心鳳茶讓人重新定義「臺味」。 三希樓｜老饕級江浙功夫菜，穩重又帶人情味的中式饗宴
位於公益路上的 三希樓 是許多臺中老饕的口袋名單。 餐點特色
三希樓的菜色以 江浙與港式料理 為主，兼顧傳統與現代風味。 用餐體驗三希樓的服務給人一種老派但貼心的感覺。 綜合評分
地址：408臺中市南屯區公益路二段95號電話：0423202322 官網：https://www.sanxilou.com.tw/ 小結語三希樓是一間「吃得出功夫」的餐廳。 一笈壽司｜低調奢華的無菜單日料，職人手藝詮釋旬味極致
在熱鬧的公益路上，一笈壽司 低調得幾乎不顯眼。 餐點特色
一笈壽司採 Omakase（無菜單料理） 形式，每一餐都由主廚根據當日食材設計。 用餐體驗整場用餐約90分鐘，節奏緩慢但沉穩。 綜合評分
地址：408臺中市南屯區公益路二段25號電話：0423206368 官網：https://www.facebook.com/YIJI.sushi/ 小結語一笈壽司是一間真正讓人「放慢呼吸」的餐廳。 茶六燒肉堂｜人氣爆棚的和牛燒肉聖地，肉香與幸福感同時滿分
若要票選公益路上「最難訂位」的餐廳，茶六燒肉堂 絕對名列前茅。 餐點特色
茶六主打 和牛燒肉套餐，價格約落在 $700–$1000 間，份量與品質兼具。 用餐體驗茶六的服務效率相當高。店員親切、換網勤快、補水速度快，整場用餐流程流暢無壓力。 綜合評分
地址：403臺中市西區公益路268號電話：0423281167 官網：https://inline.app/booking/-L93VSXuz8o86ahWDRg0:inline-live-karuizawa/-LUYUEIOYwa7GCUpAFWA 小結語茶六燒肉堂用「穩定品質＋輕奢氛圍」抓住了臺中年輕族群的心。 吃完10家公益路餐廳後的心得與結語吃完這十家餐廳後，臺中公益路不只是一條美食街，而是一段生活風景線。 有的餐廳講究細膩與儀式感，像 一頭牛日式燒肉 與 一笈壽司，讓人感受到食材最純粹的美好 有的則以親切與溫度打動人心，像 加分昆布鍋物、永心鳳茶，讓人明白吃飯不只是為了飽足，而是一種被照顧的幸福。 而像茶六燒肉堂、TANG Zhan 湯棧 這類人氣名店，則用穩定的品質與熱絡的氛圍，成為許多臺中人心中「想吃肉就去那裡」的代名詞。 這十家店，構成了公益路最動人的縮影 有華麗的，也有溫柔的；有傳統的，也有創新的。 每一家都在自己的風格裡發光，讓人吃到的不只是料理，而是一種生活的溫度與節奏。 對我而言，這不僅是一場美食旅程，更是一趟關於「臺中味道」的回憶之旅。 FAQ：關於臺中公益路美食常見問題Q1：公益路哪一區的餐廳最集中？ Q2：需要提前訂位嗎？ 最後的話若要用一句話形容這趟美食之旅，我會說： 三希樓團體宴客合適嗎？ 如果你也和我一樣喜歡用味蕾探索一座城市，那就把這篇公益路美食攻略收藏起來吧。印月餐廳春酒場面夠體面嗎？ 無論是約會、慶生、家庭聚餐，或只是想犒賞一下辛苦的自己——這條路上永遠會有一間剛剛好的餐廳在等你。一頭牛日式燒肉調味偏重嗎？ 下一餐，不妨從這10家開始。一笈壽司值得專程去嗎？ 打開手機、約上朋友，讓公益路成為你生活裡最容易抵達的小確幸。茶六燒肉堂值得推薦嗎？ 如果你有私心愛店，也歡迎留言分享，KoDō 和牛燒肉需要訂位嗎？ 你的推薦，可能讓我下一趟美食旅程變得更精彩。NINI 尼尼臺中店真的有那麼好吃嗎？ The spliceosome is a large and complex molecular machine within the cell that removes introns from pre-messenger RNA (pre-mRNA), allowing for the proper assembly of protein-coding sequences, or exons. This essential process of RNA splicing enables the accurate translation of genetic information, facilitating the diversity and functionality of proteins in eukaryotic organisms. Researchers unveil the inner mechanisms of the most intricate and complex molecular machine in human biology. Scientists at the Centre for Genomic Regulation (CRG) in Barcelona have developed the first comprehensive blueprint of the human spliceosome, the most complex and intricate molecular machine found in every cell. This groundbreaking achievement, over a decade in the making, was published in the journal Science. The spliceosome edits genetic messages transcribed from DNA, allowing cells to create different versions of a protein from a single gene. The vast majority of human genes – more than nine in ten – are edited by the spliceosome. Errors in the process are linked to a wide spectrum of diseases including most types of cancer, neurodegenerative conditions, and genetic disorders. The sheer number of components involved and the intricacy of its function has meant the spliceosome has remained elusive and uncharted territory in human biology – until now. The blueprint reveals that individual components of the spliceosome are far more specialized than previously thought. Many of these components have not been considered for drug development before because their specialized functions were unknown. The discovery can unlock new treatments that are more effective and have fewer side effects. “The layer of complexity we’ve uncovered is nothing short of astonishing. We used to conceptualize the spliceosome as a monotonous but important cut-and-paste machine. We now see it as a collection of many different flexible chisels that allow cells to sculpt genetic messages with a degree of precision worthy of marble-sculpting grandmasters from antiquity. By knowing exactly what each part does, we can find completely new angles to tackle a wide spectrum of diseases,” says ICREA Research Professor Juan Valcárcel, lead author of the study and researcher at the CRG. The most complex molecular machine in human biology Every cell in the human body relies on precise instructions from DNA to function correctly. These instructions are transcribed into RNA, which then undergoes a crucial editing process called splicing. During splicing, non-coding segments of RNA are removed, and the remaining coding sequences are stitched together to form a template or recipe for protein production. While humans have about 20,000 protein-coding genes, splicing allows the production of at least five times as many proteins, with some estimates suggesting humans can create more than 100,000 unique proteins. The spliceosome is the collection of 150 different proteins and five small RNA molecules which orchestrate the editing process, but until now, the specific roles of its numerous components were not fully understood. The team at the CRG altered the expression of 305 spliceosome-related genes in human cancer cells one by one, observing the effects of splicing across the entire genome. Dr. Malgorzata Rogalska studying cell cultures at the Centre for Genomic Regulation in Barcelona. Credit: Centro de Regulación Genómica Their work revealed that different components of the spliceosome have unique regulatory functions. Crucially, they found that proteins within the spliceosome’s core are not just idle support workers but instead have highly specialized jobs in determining how genetic messages are processed, and ultimately, influence the diversity of human proteins. For example, one component selects which RNA segment is removed. Another component ensures cuts are made at the right place in the RNA sequence, while another one behaves like a chaperone or security guard, keeping other components from acting too prematurely and ruining the template before it’s finished. The authors of the study compare their discovery to a busy post-production set in film or television, where genetic messages transcribed from DNA are assembled like raw footage. “You have many dozens of editors going through the material and making rapid decisions on whether a scene makes the final cut. It’s an astonishing level of molecular specialization at the scale of big Hollywood productions, but there’s an unexpected twist. Any one of the contributors can step in, take charge, and dictate the direction. Rather than the production falling apart, this dynamic results in a different version of the movie. It’s a surprising level of democratization we didn’t foresee,” says Dr. Malgorzata Rogalska, co-corresponding author of the study. Cancer’s ‘Achilles’ Heel’ One of the most significant findings in the study is that the spliceosome is highly interconnected, where disrupting one component can have widespread ripple effects throughout the entire network. For example, the study manipulated the spliceosome component SF3B1, which is known to be mutated in many cancers including melanoma, leukemia, and breast cancer. It is also a target for anti-cancer drugs, though the exact of mechanisms of action has been unclear – until now. The study found that altering the expression of SF3B1 in cancer cells sets off a cascade of events that affected a third of the cell’s entire splicing network, causing a chain reaction of failures which overwhelm the cell’s ability to fuel growth. The finding is promising because traditional therapies, for example, those targeting mutations in DNA, often cause cancer cells to become resistant. One of the ways cancers adapt is by rewiring their splicing machinery. Targeting splicing can push diseased cells past a tipping point that cannot be compensated for, leading to their self-destruction. “Cancer cells have so many alterations to the spliceosome that they are already at the limit of what’s biologically plausible. Their reliance on a highly interconnected splicing network is a potential Achilles’ heel we can leverage to design new therapies, and our blueprint offers a way of discovering these vulnerabilities” says Dr. Valcárcel. “This pioneering research illuminates the complex interplay between components of the spliceosome, revealing insight into its mechanistic and regulatory functions. These findings not only advance our understanding of spliceosome function but also open potential opportunities to target RNA processing for therapeutic interventions in diseases associated with splicing dysregulation” says Dom Reynolds, CSO at Remix Therapeutics, a clinical-stage biotechnology company in Massachusetts who collaborated with the CRG on the study. Bringing splicing treatments into the mainstream Apart from cancer, there are many other diseases caused by faulty RNA molecules produced by mistakes in splicing. With a detailed map of the spliceosome, which the authors of the study have made publicly available, researchers can now help pinpoint exactly where the splicing errors are occurring in a patient’s cells. “We wanted this to be a valuable resource for the research community,” says Dr. Valcárcel. “Drugs correcting splicing errors have revolutionized the treatment of rare disorders like spinal muscular atrophy. This blueprint can extend that success to other diseases and bring these treatments into the mainstream,” he adds. “Current splicing treatments are focused on rare diseases, but they are just the tip of the iceberg. We are moving into an era where we can address diseases at the transcriptional level, creating disease-modifying drugs rather than merely tackling symptoms. The blueprint we’ve developed paves the way for entirely new therapeutic approaches. It’s only a matter of time,” concludes Dr. Rogalska. Reference: “Transcriptome-wide splicing network reveals specialized regulatory functions of the core spliceosome” by Malgorzata E. Rogalska, Estefania Mancini, Sophie Bonnal, André Gohr, Bryan M. Dunyak, Niccolò Arecco, Peter G. Smith, Frédéric H. Vaillancourt and Juan Valcárcel, 31 October 2024, Science. DOI: 10.1126/science.adn8105 Phylogenetic trees, starting with an individual cancer cell. Each color represents a different location in the body. A very colorful tree shows a highly metastatic phenotype, where a cell’s descendants jumped many times between different tissues. A tree that is primarily one color represents a less metastatic cell. Credit: Jeffrey Quinn/Whitehead Institute Using CRISPR technology, researchers are tracking the lineage of individual cancer cells as they proliferate and metastasize in real-time. When cancer is confined to one spot in the body, doctors can often treat it with surgery or other therapies. Much of the mortality associated with cancer, however, is due to its tendency to metastasize, sending out seeds of itself that may take root throughout the body. The exact moment of metastasis is fleeting, lost in the millions of divisions that take place in a tumor. “These events are typically impossible to monitor in real-time,” says Jonathan Weissman, MIT professor of biology and Whitehead Institute for Biomedical Research member. Now, researchers led by Weissman, who is also an investigator with the Howard Hughes Medical Institute, have turned a CRISPR tool into a way to do just that. In a paper published on January 21, 2021, in Science, Weissman’s lab, in collaboration with Nir Yosef, a computer scientist at the University of California at Berkeley, and Trever Bivona, a cancer biologist at the University of California at San Francisco, treats cancer cells the way evolutionary biologists might look at species, mapping out an intricately detailed family tree. By examining the branches, they can track the cell’s lineage to find when a single tumor cell went rogue, spreading its progeny to the rest of the body. “With this method, you can ask questions like, ‘How frequently is this tumor metastasizing? Where did the metastases come from? Where do they go?’” Weissman says. “By being able to follow the history of the tumor in vivo, you reveal differences in the biology of the tumor that were otherwise invisible.” Scratch Paper Cells Scientists have tracked the lineages of cancer cells in the past by comparing shared mutations and other variations in their DNA blueprints. These methods, however, depend to a certain extent on there being enough naturally occurring mutations or other markers to accurately show relationships between cells. That’s where Weissman and co-first authors Jeffrey Quinn, then a postdoc in Weissman’s lab, and Matthew Jones, a graduate student in Weissman’s lab, saw an opportunity to use CRISPR technology — specifically, a method developed by Weissman Lab member Michelle Chan to track embryo development — to facilitate tracking. Instead of simply hoping that a cancer lineage contained enough lineage-specific markers to track, the researchers decided to use Chan’s method to add in markers themselves. “Basically, the idea is to engineer a cell that has a genomic scratchpad of DNA, that then can be ‘written’ on using CRISPR,” Weissman says. This ‘writing’ in the genome is done in such a way that it becomes heritable, meaning a cell’s grand-offspring would have the ‘writing’ of its parent cells and grandparent cells recorded in its genome. To create these special “scratchpad” cells, Weissman engineered human cancer cells with added genes: one for the bacterial protein Cas9 — the famed “molecular scissors” used in CRISPR genome editing methods — others for glowing proteins for microscopy, and a few sequences that would serve as targets for the CRISPR technology. They then implanted thousands of the modified human cancer cells into mice, mimicking a lung tumor (a model developed by collaborator Bivona). Mice with human lung tumors often exhibit aggressive metastases, so the researchers reasoned they would provide a good model for tracking cancer progression in real-time. As the cells began to divide, Cas9 made small cuts at these target sites. When the cell repaired the cuts, it patched in or deleted a few random nucleotides, leading to a unique repair sequence called an indel. This cutting and repairing happened randomly in nearly every generation, creating a map of cell divisions that Weissman and the team could then track using special computer models that they created by working with Yosef, a computer scientist. Revealing the Invisible Tracking cells this way yielded some interesting results. For one thing, individual tumor cells were much different from each other than the researchers expected. The cells the researchers used were from an established human lung cancer cell line called A549. “You’d think they would be relatively homogeneous,” Weissman says. “But in fact, we saw dramatic differences in the propensity of different tumors to metastasize — even in the same mouse. Some had a very small number of metastatic events, and others were really rapidly jumping around.” To find out where this heterogeneity was coming from, the team implanted two clones of the same cell in different mice. As the cells proliferated, the researchers found that their descendants metastasized at a remarkably similar rate. This was not the case with the offspring of different cells from the same cell line — the original cells had apparently evolved different metastatic potentials as the cell line was maintained over many generations. The scientists next wondered what genes were responsible for this variability between cancer cells from the same cell line. So they began to look for genes that were expressed differently between nonmetastatic, weakly metastatic, and highly metastatic tumors. Many genes stood out, some of which were previously known to be associated with metastasis — although it was not clear whether they were driving the metastasis or simply a side effect of it. One of them, the gene that codes for the protein Keratin 17, is much more strongly expressed in low metastatic tumors than in highly metastatic tumors. “When we knocked down or overexpressed Keratin 17, we showed that this gene was actually controlling the tumors’ invasiveness,” Weissman says. Being able to identify metastasis-associated genes this way could help researchers answer questions about how tumors evolve and adapt. “It’s an entirely new way to look at the behavior and evolution of a tumor,” Weissman says. “We think it can be applied to many different problems in cancer biology.” Where Did You Come From, Where Did You Go? Weissman’s CRISPR method also allowed the researchers to track with more detail where metastasizing cells went in the body, and when. For example, the progeny of one implanted cancer cell underwent metastasis five separate times, spreading each time from the left lung to other tissues such as the right lung and liver. Other cells made a jump to a different area, and then metastasized again from there. These movements can be mapped neatly in phylogenetic trees (see image), where each color represents a different location in the body. A very colorful tree shows a highly metastatic phenotype, where a cell’s descendants jumped many times between different tissues. A tree that is primarily one color represents a less metastatic cell. Mapping tumor progression in this way allowed Weissman and his team to make a few interesting observations about the mechanics of metastasis. For example, some clones seeded in a textbook way, traveling from the left lung, where they started, to distinct areas of the body. Others seeded more erratically, moving first to other tissues before metastasizing again from there. One such tissue, the mediastinal lymph tissue that sits between the lungs, appears to be a hub of sorts, says co-first author Jeffrey Quinn. “It serves as a way station that connects the cancer cells to all of this fertile ground that they can then go and colonize,” he says. Therapeutically, the discovery of metastasis “hubs” like this could be extremely useful. “If you focus cancer therapies on those places, you could then slow down metastasis or prevent it in the first place,” Weissman says. In the future, Weissman hopes to move beyond simply observing the cells and begin to predict their behavior. “It’s like with Newtonian mechanics — if you know the velocity and position and all the forces acting on a ball, you can figure out where the ball is going to go at any time in the future,” Weissman says. “We’re hoping to do the same thing with cells. We want to construct essentially a function of what is driving differentiation of a tumor, and then be able to measure where they are at any given time, and predict where they’re going to be in the future.” The researchers are optimistic that being able to track the family trees of individual cells in real-time will prove useful in other settings as well. “I think that it’s going to unlock a whole new dimension to what we think about as a measurable quantity in biology,” says co-first author Matthew Jones. “That’s what’s really cool about this field in general is that we’re redefining what’s invisible and what is visible.” Reference: “Single-cell lineages reveal the rates, routes, and drivers of metastasis in cancer xenografts” by Jeffrey J. Quinn, Matthew G. Jones, Ross A. Okimoto, Shigeki Nanjo, Michelle M. Chan, Nir Yosef, Trever G. Bivona and Jonathan S. Weissman, 21 January 2021, Science. DOI: 10.1126/science.abc1944 The research team has increased the sensitivity of the acoustic reporter genes technique to the extent that it can now image a single cell carrying an acoustic reporter gene within body tissue. Credit: Barth van Rossum for Caltech If you are a researcher who wants to see how just a few cells in an organism are behaving, it is no simple task. The human body contains approximately 37 trillion cells; the fruit fly flitting around the overripe bananas on your counter might have 50,000 cells. Even Caenorhabditis elegans, a tiny worm commonly used in biological research, can have as many as 3,000 cells. So, how do you monitor a couple of microscopic specks amid all of that? Scientists working in the Caltech lab of Mikhail G. Shapiro, professor of chemical engineering and Heritage Medical Research Institute Investigator, have found a way. The new technique makes use of so-called acoustic reporter genes, of which Shapiro has been a pioneering developer. To understand acoustic reporter genes, first know that reporter genes are a specialized snippet of DNA that researchers can insert into an organism’s genome to help them understand what it is doing. Historically, reporter genes have encoded fluorescent proteins. For example, if a researcher inserts one of these reporter genes next to a gene they want to study—say, the gene that is responsible for the development of neurons—the activation of those neuron genes will also produce fluorescent protein molecules. When the right kind of light is shined upon those cells, they will light up, kind of like how a highlighter can mark a specific passage in a book. These fluorescent reporter genes have a big disadvantage though: light does not penetrate very far through living tissues. So, Shapiro has developed reporter genes that use sound instead of light. These genes, when inserted into a cell’s genome, cause it to produce microscopic hollow protein structures known as gas vesicles. These vesicles are normally found in certain species of bacteria that use them to stay afloat in water, but they also have the useful property of “ringing” when struck by ultrasound waves. The idea is that when a cell producing these vesicles is imaged with ultrasound, it will send out an acoustic signal announcing its presence, allowing researchers to see where it is and what it is doing. This technique has been used to show the activity of enzymes in cells in previous work by Shapiro’s lab. In their latest paper, the research team describes how it has increased the sensitivity of that technique so much that it can now image a single cell, located within body tissue, that is carrying an acoustic reporter gene. Single cells traveling through the liver of a mouse are highlighted by a new imaging technique developed in Mikhail Shapiro’s lab. Credit: Caltech/Daniel Sawyer, Shapiro Lab “In comparison to previous work on gas vesicles, this paper allows us to see much smaller quantities of these gas vesicles,” says Daniel Sawyer (PhD ’21), lead author and former bioengineering PhD student in Shapiro’s lab. “This is like going from a satellite that can see the lights of a small town to one that can see the light from a single lamppost.” Their improvements represent an increase of more than 1000-fold in sensitivity over the previous technique they had been using for imaging cells carrying the acoustic reporter genes. The difference lies in the ultrasound they use and how the gas vesicles respond to it. Whereas the previous imaging technique relied on the vesicles ringing like a bell that has been struck, the new technique uses stronger ultrasound that “pops” the vesicles like a balloon. “The vesicles produce a very strong signal in that moment,” Shapiro says. “Then the vesicles break and stop making a signal. We’re looking for the little blip.” That blip is so clear that it can easily be detected by the researchers, even amid all the background noise produced by ultrasound penetrating through tissue. Shapiro says recent work on engineered strains of injectable bacteria that attack cancer cells, or “tumor-homing” bacteria, creates a need for better ways to track these cells to see where in the body they land. The researchers showed that when the bacteria were also engineered to carry the gas-vesicle gene, it was possible to track individual bacterial cells as they entered and traveled through the liver after being injected into the bloodstream. Sawyer says this level of sensitivity is necessary if researchers want to use ultrasound for studying the composition of the gut microbiome, which, when disrupted, can influence conditions like Alzheimer’s disease and autism. “There are so many species of bacteria in your gut, and some are so rare that you need something sensitive enough to see just the few of them deep inside the body,” he says. Does popping the vesicles inside cells harm the cells? No, not really. “The short answer is no, and the long answer is no in most practical cases,” Sawyer says. “There are some cases where single bacterial cells that are very small and have a very large amount of these gas vesicles are harmed, but it doesn’t make much of a difference to the bacterial population if a few of them become less viable. And in mammalian cells, we saw no negative effect.” Shapiro and Sawyer are pursuing two paths for their research going forward. One path will build on what the researchers have already developed to create more advanced imaging techniques. That will involve engineering and testing new kinds of vesicles that have different properties, such as vesicles that pop more easily, or vesicles that are more robust, or smaller vesicles that can fit into places that larger vesicles cannot. The other path is finding practical applications for the technology they have developed, Sawyer says. “In the optical microscopy field, there was this co-evolution of optical probes and microscopy methods with techniques like two-photon microscopy and light-sheet microscopy [both are types of fluorescent microscopy],” Shapiro says. “Danny’s paper is part of the development of the ultrasound analog of those imaging techniques.” The paper describing their research, titled, “Ultrasensitive ultrasound imaging of gene expression with signal unmixing,” appears in the August 6 issue of the journal Nature Methods. Co-authors include Avinoam Bar Zion, the visitor in chemical engineering; Arash Farhadi (PhD ’20); bioengineering graduate student Shirin Shivaei; chemical engineering graduate student Bill Ling; and Audrey Lee-Gosselin, formerly of Caltech. Reference: “Ultrasensitive ultrasound imaging of gene expression with signal unmixing” by Daniel P. Sawyer, Avinoam Bar-Zion, Arash Farhadi, Shirin Shivaei, Bill Ling, Audrey Lee-Gosselin and Mikhail G. Shapiro, 5 August 2021, Nature Methods. DOI: 10.1038/s41592-021-01229-w Funding for the research was provided by the National Institutes of Health. Mikhail Shapiro is an affiliated faculty member of the Tianqiao and Chrissy Chen Institute for Neuroscience. RRG455KLJIEVEWWF |
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