Here's a question for you: how many different scents do you think you can smell, and maybe even identify with accuracy? 100? 300? 1,000? One study estimates that humans can detect up to one trillion different odors. A trillion. It's hard to imagine, but your nose has the molecular machinery to make it happen.
我要問你們一個問題: 你們知道你可以聞到多少種氣味? 甚至精確地辨識出來? 100 種? 300 種? 1000 種? 一個研究估算,人類可以分辨出 高達一兆種不同氣味。 一兆種。 這個數字很難想像, 但鼻子所具有的分子機制 能夠使之成爲現實。
Olfactory receptors -- tiny scent detectors -- are packed into your nose, each one patiently waiting to be activated by the odor, or ligand, that it's been assigned to detect. It turns out we humans, like all vertebrates, have lots of olfactory receptors. In fact, more of our DNA is devoted to genes for different olfactory receptors than for any other type of protein.
嗅覺接受器── 微小的氣味探測器── 都聚集在你的鼻子裡, 每一個都耐心等待著氣味來激活它, 也就是被配體激活, 被指定來檢測。 事實上我們人類 和所有脊椎動物一樣, 有很多嗅覺接受器。 事實上,我們的 DNA 中被用來表達 不同的嗅覺接受器的基因數量, 多於任何其他的蛋白質結構。
Why is that? Could olfactory receptors be doing something else in addition to allowing us to smell?
為什麽會這樣呢? 難道嗅覺接受器還有別種用途, 除了讓我們聞到東西?
In 1991, Linda Buck and Richard Axel uncovered the molecular identity of olfactory receptors -- work which ultimately led to a Nobel Prize. At the time, we all assumed that these receptors were only found in the nose. However, about a year or so later, a report emerged of an olfactory receptor expressed in a tissue other than the nose. And then another such report emerged, and another. We now know that these receptors are found all over the body, including in some pretty unexpected places -- in muscle, in kidneys, lungs and blood vessels.
1991 年琳達.巴克 和理察.阿克塞爾發現了 嗅覺接受器的分子識別機制。 最終得到了諾貝爾獎。 當時, 我們都以為那些接受器 只存在鼻子裡。 但是,大概一年之後 一篇報告顯示嗅覺接受器 也存在於鼻子以外的身體組織。 接著又有一個類似的報告出現, 一個接一個。 我們現在知道全身上下都可以 找到這些接受器, 包括那些意想不到的部位── 在肌肉裡, 在腎臟裡, 在肺臟裡, 在血管裡。
But what are they doing there? Well, we know that olfactory receptors act as sensitive chemical sensors in the nose -- that's how they mediate our sense of smell. It turns out they also act as sensitive chemical sensors in many other parts of the body. Now, I'm not saying that your liver can detect the aroma of your morning coffee as you walk into the kitchen. Rather, after you drink your morning coffee, your liver might use an olfactory receptor to chemically detect the change in concentration of a chemical floating through your bloodstream.
但它們在那裡做什麼? 我們知道嗅覺接受器 是鼻子中敏感的化學感測器── 它們傳達我們的嗅覺。 然而嗅覺接受器 作為敏感的化學感測器, 也在身體的其他部位起作用。 我不是說你的肝能聞到 你早晨咖啡的香氣, 當你走進廚房時。 不如說,你喝了早晨咖啡後, 你的肝可能啓用一種嗅覺接受器, 用化學方式探測 某種在血液中的 化學物其濃度的變化。
Many cell types and tissues in the body use chemical sensors, or chemosensors, to keep track of the concentration of hormones, metabolites and other molecules, and some of these chemosensors are olfactory receptors. If you are a pancreas or a kidney and you need a specialized chemical sensor that will allow you to keep track of a specific molecule, why reinvent the wheel?
身體裡很多類型的細胞和組織 都會使用化學感測器, 或稱為化學受器, 來追蹤賀爾蒙、代謝物 及其他分子的濃度, 而其中一些化學感測器 就是嗅覺受器。 假設你是胰腺或腎臟, 你需要一種特製的化學感測器, 來幫你追蹤一個特定的分子。 那為什麼要浪費時間重複發明呢?
One of the first examples of an olfactory receptor found outside the nose showed that human sperm express an olfactory receptor, and that sperm with this receptor will seek out the chemical that the receptor responds to -- the receptor's ligand. That is, the sperm will swim toward the ligand. This has intriguing implications. Are sperm aided in finding the egg by sniffing out the area with the highest ligand concentration?
有一個早期發現 鼻子以外有嗅覺接受器的例子, 顯示人的精子裡 具有嗅覺接受器結構, 精子及嗅覺接受器就會找出 會與接受器產生反應化學物質── 嗅覺接受器的配體。 也就是說,精子會游向配體。 這裡頭的含意使人好奇。 精子是否被幫助去尋找卵子? 通過嗅覺接收器聞出 最高濃度的配體區域?
I like this example because it clearly demonstrates that an olfactory receptor's primary job is to be a chemical sensor, but depending on the context, it can influence how you perceive a smell, or in which direction sperm will swim, and as it turns out, a huge variety of other processes. Olfactory receptors have been implicated in muscle cell migration, in helping the lung to sense and respond to inhaled chemicals, and in wound healing.
我喜歡這個例子,是因為這清楚顯示 嗅覺接受器的主要工作 是化學感測器, 但取決於環境, 那可能影響你如何感知氣味, 或影響精子將會游動的方向。 實際上, 涉及一系列其他多種的程序。 嗅覺接收器參與肌肉細胞的移動, 來幫助肺去感測被吸進來的 化學物質並產生反應, 還有幫助傷口癒合。
Similarly, taste receptors once thought to be found only in the tongue, are now known to be expressed in cells and tissues throughout the body. Even more surprisingly, a recent study found that the light receptors in our eyes also play a role in our blood vessels.
同樣,味覺收器曾被認爲 只存在於舌頭上。 現在味覺接收器表現在 身體許多其它細胞和組織裡。 甚至更讓人吃驚的是, 在一個最近的研究發現, 在我們眼中的光感接收器在我們的 血液循環系統中也起一定的作用。
In my lab, we work on trying to understand the roles of olfactory receptors and taste receptors in the context of the kidney. The kidney is a central control center for homeostasis. And to us, it makes sense that a homeostatic control center would be a logical place to employ chemical sensors. We've identified a number of different olfactory and taste receptors in the kidney, one of which, olfactory receptor 78, is known to be expressed in cells and tissues that are important in the regulation of blood pressure. When this receptor is deleted in mice, their blood pressure is low. Surprisingly, this receptor was found to respond to chemicals called short-chain fatty acids that are produced by the bacteria that reside in your gut -- your gut microbiota. After being produced by your gut microbiota, these chemicals are absorbed into your bloodstream where they can then interact with receptors like olfactory receptor 78, meaning that the changes in metabolism of your gut microbiota may influence your blood pressure.
在我的實驗室, 我們正在試圖去理解 嗅覺和味覺收器 在腎臟工作中起的作用。 腎是我們體內恆定的主要控制中心。 對於我們來說, 體內恆定控制中心 運用一系列的化學感應器 是完全合情合理的。 我們已經發現並識別了 在腎的工作中起作用的多種 嗅覺和味覺接收器。 其中之一是第 78 號嗅覺接收器。 事實上,它在 各種細胞和組織裡表現, 有控制血壓的重要作用。 我們發現把小白鼠體内的 這個嗅覺接收器拿掉, 小白鼠的血壓變低。 令人驚訝的是,這個接收器 對某種化學物質── 就是短鏈脂肪酸──產生反應, 它是由生活在 腸道裡的細菌產生的── 腸道菌叢。 短鏈脂肪酸被腸道菌叢製作出來後, 這些化學物質被吸收進血液中。 由此,再與嗅覺和味覺接收器 互相作用和影響, 例如,嗅覺接收器 78, 也就是説,你的腸道菌叢的 新陳代謝的變化 可能會影響你的血壓。
Although we've identified a number of different olfactory and taste receptors in the kidney, we've only just begun to tease out their different functions and to figure out which chemicals each of them responds to. Similar investigations lie ahead for many other organs and tissues -- only a small minority of receptors has been studied to date. This is exciting stuff. It's revolutionizing our understanding of the scope of influence for one of the five senses. And it has the potential to change our understanding of some aspects of human physiology. It's still early, but I think we've picked up on the scent of something we're following.
儘管我們辨識了幾種不同的 嗅覺和味覺接收器, 主要是在腎裡, 我們才剛剛開始試著找出 它們各種不同的功能, 並且找出它們分別對什麽 化學物質發生反應。 擺在我們前面的工作是對 其他器官和組織開展同樣的研究。 目前我們只探究了 非常小部分的接收器。 這可是令人激動的發展。 這些發現革新了 我們對嗅覺影響層面的理解, 而這只是五感覺之一。 它具有很大潛力改變 人類對人體生理學的某些理解。 雖然這些研究還處於早期階段, 但是我們認爲我們已經嗅到了 追尋已久的成功的氣味。
(Laughter)
(笑聲)
Thank you.
謝謝。
(Applause)