Like a computer, cells must process information from the outside world before they respond. Scientists have now developed a powerful new way to observe the internal discussions responsible for cellular decisions.

如同一部電腦，細胞在其作出反應之前，必須處理來自外界的信息。目前，科學家們業已研發出一種強有力的新方法，來觀察導致細胞諸多決擇的內部討論。

圖1.一種新的造影技術，使得即時且同時觀察多個細胞信號成為可能。分子信息簇(綠色)察覺，之後研究人員能標記及識別(多種顏色)的上述信號。該方法賦予了科學家們一種，有關細胞活動之交響樂的詳細視圖。  (圖援用自原文)

A new imaging technology lets scientists spy on the flurry of messages passed within cells as they do . . . potentially everything.

一種新的造影技術，使科學家們能監視，細胞進行可能之每件事時，於其內傳遞的混亂信息。

Until now, most scientists could visualize only one or two of these intracellular signals at a time, says Howard Hughes Medical Institute Investigator Ed Boyden of the Massachusetts Institute of Technology. His team’s new approach could make it possible to see as many signals as you want – in real time, at once, Boyden says – giving researchers a more detailed view of cells’ internal discussions than ever before.

美國霍華德休斯醫學研究所調查研究員，隸屬麻省理工學院的Ed Boyden表示，直到目前，大多數科學家一次只能視覺化，一個或兩個這些細胞內的信號。其團隊的新方法可能使人們，即時且同時觀察想要的諸多信號，成為可能。他表示，這賦予了研究人員們，有關細胞內部的討論，比在此之前更詳細的視圖。

In tests with neurons, the researchers examined five signals involved in processes such as learning and memory, Boyden and his colleagues report November 23, 2020, in the journal Cell. “You could apply this technology to all sorts of biological mysteries,” he says. “Every cell works due to all the signals inside it.” Because signaling contributes to all biological processes, a better means to study it could illuminate a host of diseases, from Alzheimer’s to diabetes and cancer.

在使用神經元的諸多測試中，此些研究人員檢查了，涉及學習及記憶等，過程的五種信號。Boyden及其同僚們，在2020年11月23日的《細胞》期刊，提出研究報告。他宣稱：「人們能將此技術應用於，一切種類之生命現象的謎團上。每一細胞的運作，是由於其內部的所有信號。由於發出信號是所有生命現象之過程的部分原因，因此研究它的更佳方法可能闡明，從阿茲海默氏症到糖尿病及癌症等，諸多疾病。」

The team’s new approach is a breakthrough, says Clifford Woolf, a neurobiologist at Harvard Medical School who was not involved with the work. He plans to use it to examine how pain-sensing neurons become more sensitive in injury or illness. With the new imaging technology, he says “we can take apart what’s happening in cells in a way that just has not been possible before.”

美國哈佛醫學院未涉及該項研究的神經生物學家，Clifford Woolf表示，該團隊的新方法是一項突破。他計劃用它來檢查，於受傷或生病時，痛覺神經元如何變得更加敏感。他表示，使用該項新造影技術，人們能以一種先前一直不可能的方法，來分析細胞內正發生什麼。

Give a computer or a human brain information, and it will crackle with electrical impulses as it prepares a response. Within cells, these impulses result in spurts of multiple molecular signals. Boyden describes this process as a group conversation. “Signals within a cell are like a set of people trying to decide what to do for the evening: they take into account many possibilities, and then decide what to collectively do,” he says.

給予電腦或人腦信息，在其準備作出反應時，會隨著電氣脈衝發出劈啪聲。在細胞內，此些脈衝導致激發出多種分子信號。Boyden記述此過程為一群交談。他宣稱：「細胞內的信號，如同一群試圖決定晚上做什麼的人：他們將諸多可能性納入考量，然後決定要集體做些什麼。」

These cellular discussions are what prompt, for example, a neuron to encode a memory or a cell to turn cancerous. Despite their importance, scientists still don’t have a strong grasp of how these signals work together to guide a cell’s behavior.

譬如，這些細胞的討論促使神經元，進行編碼記憶或使細胞癌變。儘管其重要性，不過科學家們對此些信號如何協同運作，來引導細胞行為，仍然沒有正確的理解。

To see cell signaling in action, scientists typically introduce genes encoding sensors connected to fluorescent proteins. These molecular reporters sense a signal and then glow a specific color under the microscope.

為了觀察運作中的細胞發信號，通常科學家們引進，被連接到螢光蛋白質之編碼感知器的基因。此些分子報告物感知信號，然後在顯微鏡下，發出特定顏色的光。

Researchers can use a different color reporter for each signal to tell the signals apart. But finding sets of reporters with colors that a microscope can differentiate is challenging. And a typical cellular conversation can involve dozens of signals – or more.

研究人員們能為每一信號，使用不同的顏色報告物，來區分此些信號。不過，發現數組顯微鏡能區分之具有顏色的報告物，是一項挑戰。而典型的細胞交談會涉及數十種信號，或更多。

Changyang Linghu and Shannon Johnson, scientists in Boyden’s lab, got around this limitation by affixing reporters to small, self-assembling proteins that act like LEGO bricks. These small proteins “clicked together,” forming clusters that were randomly scattered across the cell like little islands.

於Boyden實驗室的科學家，Changyang Linghu及Shannon Johnson，藉由將報告物固定於，類似樂高積木之小分子、行自組合的蛋白質上。此些小分子蛋白質“聚集”，形成像諸多類似小島物，隨機散佈於整個細胞的簇。

Each cluster, which appears under the microscope as a luminescent dot, reports only one type of cellular signal. “It’s like having some islands with thermometers to report temperature and other islands with barometers measuring pressure,” Johnson says.

在顯微鏡下，每一簇以一個發冷光的點出現，報告物只是一種細胞信號。Johnson宣稱：「這像是有些報告溫度之具有溫度計，及其他具有測量壓力之氣壓計的類似島物。」

In experiments with neurons, the team created clusters that each glowed upon detection of one of five different signals, including calcium ions and other important signaling molecules. After imaging the live cells, the researchers attached molecular labels to the glowing dots to identify the reporters located there.

在使用神經元的諸多實驗中，該團隊創造了，在檢測到包括，鈣離子及其他重要發信號分子等，五種不同信號之一時，每一發光的簇。

Using computer analyses, the team turned the dots magenta, yellow, and other colors, depending on whether they represented calcium or another signal. This let them see which signals were switching on and off across a cell’s interior.

使用電腦分析，該團隊將這些點變成，取決於是否它們代表鈣或其他信號的洋紅色、黃色及其他顏色。這使他們能觀察，於細胞內部，哪些信號被開啟及關閉。

By monitoring so many signals at once, the team was able to figure out how each signal related to one another. “Teasing apart such relationships could help scientists understand complex processes ­– like learning, ” Linghu says.

藉由同時監視這麼多信號，該團隊能理解每一信號，如何相互相關聯。Linghu宣稱：「找出此類關係可能有助於助科學家們瞭解，諸如學習等複雜過程。」

He likens a cell to an orchestra and its signals to a symphony. “It’s difficult to fully appreciate a symphony by listening to just a single instrument,” he says. Because the new technique lets scientists observe multiple signals at the same time, “we can understand the symphony of cellular activities.”

他將細胞比作一個樂團，及其信號比作一個交響樂。 他宣稱：「藉由僅傾聽一種樂器，這很難充分欣賞交響樂。」由於該項新技術使科學家們能同時觀察多個信號，因此他們能理解細胞活動的交響曲。

Boyden’s team estimates it may be possible to detect as many as 16 signals with their technology, but improvements in genetic engineering techniques could raise that number significantly. “Potentially, you could look at dozens, hundreds, or even more signals,” he says. “The next challenge,” Boyden says, “is getting sensors for all of those signals into a cell.”

Boyden的團隊估計，使用他們的技術或許可能檢測多達16種信號。不過，在基因工程技術上的諸多改進，可能顯著提升那數字。他宣稱：「潛在上，可能觀察數十、數百或甚至更多的信號。下一個挑戰是將所有那些信號的感知器，置放入細胞中。」

原文網址：https://www.hhmi.org/news/recording-the-symphony-of-cellular-signals-that-drive-biology

翻譯：許東榮