{"id":34967,"date":"2023-09-20T04:41:41","date_gmt":"2023-09-20T04:41:41","guid":{"rendered":"https:\/\/www.lifeandnews.com\/articles\/?p=34967"},"modified":"2023-09-22T10:21:47","modified_gmt":"2023-09-22T10:21:47","slug":"seeing-what-the-naked-eye-cant-%e2%88%92-4-essential-reads-on-how-scientists-bring-the-microscopic-world-into-plain-sight","status":"publish","type":"post","link":"https:\/\/www.lifeandnews.com\/articles\/seeing-what-the-naked-eye-cant-%e2%88%92-4-essential-reads-on-how-scientists-bring-the-microscopic-world-into-plain-sight\/","title":{"rendered":"Seeing what the naked eye can\u2019t \u2212 4 essential reads on how scientists bring the microscopic world into plain sight"},"content":{"rendered":"

The microscope is an iconic symbol of the life sciences \u2013 and for good reason. From the discovery of the existence of cells<\/a> to the structure of DNA<\/a>, microscopy has been a quintessential tool of the field, unlocking new dimensions of the living world not only for scientists but also for the general public.<\/p>\n

For the life sciences, where understanding the function of a living thing often requires interpreting its form, imaging is vital to confirming theories and revealing what is yet unknown.<\/p>\n

This selection of stories from The Conversation\u2019s archive presents a few ways in which microscopy has contributed to different forms of scientific knowledge, including techniques that take visualization beyond sight altogether.<\/p>\n

1. Seeing as identifying<\/h2>\n

Over the past few centuries, the microscope has undergone a gradual but significant evolution. Each advance has allowed researchers to see increasingly smaller and more fragile structures and biomolecules at increasingly higher resolution \u2013 from cells, to the structures within cells, to the structures within the structures within cells, down to atoms.<\/p>\n

But there is still a resolution gap between the smallest and largest structures of the cell. Biophysicist Jeremy Berg<\/a> drew an analogy to Google Maps: Though scientists could see the city as a whole and individual houses, they couldn\u2019t make out the neighborhoods. <\/p>\n

\u201cSeeing these neighborhood-level details is essential to being able to understand how individual components work together in the environment of a cell,\u201d he writes.<\/p>\n

Scientists are working to bridge that resolution gap. Improvements to the 2014 Nobel Prize-winning superresolution microscopy<\/a>, for example, have enhanced the study of lengthy processes like cell division by capturing images across a range of size and time scales simultaneously, bringing clarity to details traditional microscopes tend to blur.<\/p>\n

\n\"Cryo-ET<\/a>
\nCryo-electron tomography shows what molecules look like in high resolution \u2013 in this case, the virus that causes COVID-19.<\/span>
\nNanographics<\/a>, CC BY-SA<\/a><\/span>
\n<\/figcaption><\/figure>\n

Another technique, cryo-electron microscopy, or cryo-EM<\/a>, won a Nobel Prize in 2017 for bringing even more complex, dynamic molecules into view by flash-freezing them. This creates a protective glasslike shell around samples as they\u2019re bombarded by a beam of electrons to create their photo op. Cryo-ET, a specialized type of cryo-EM, can construct 3D images of molecular structures within their natural environments. <\/p>\n

These techniques not only generate images at or near atomic resolution but also preserve the natural shape of difficult-to-capture biomolecules of interest. Researchers were able to use cryo-EM, for instance, to capture the elusive structure of the protein on the surface of the shape-shifting hepatitis C virus<\/a>, providing key information for a future vaccine.<\/p>\n

Further enhancements to science\u2019s visual acuity will reveal more of the fine details of the building blocks of life. <\/p>\n

\u201cI anticipate seeing new theories on how we understand cells, moving from disorganized bags of molecules to intricately organized and dynamic systems,\u201d writes Berg.<\/p>\n

2. Seeing as scoping<\/h2>\n

Microscopy images are often framed as snapshots \u2013 circumscribed parts of a whole that have been magnified to reveal their hidden features. But nothing in an organism works in isolation. After discerning individual components, scientists are tasked with charting how they interact with each other in the macrosystem of the body. Figuring this out requires not only identifying every component that makes up a particular cell, tissue and organ but also placing them in relation to each other \u2013 in other words, making a map.<\/p>\n

Researchers have been charting the brain by stitching together multiple snapshots like a photo mosaic. They use different techniques to label a specific cell type and then image the whole brain at high resolution. Layer by layer, each run-through creates an increasingly detailed and more complete model. Neuroscientist Yongsoo Kim<\/a> likens the process to a satellite image of the brain<\/a>. Combining millions of these photos allows researchers to zoom into the weeds and zoom out to a bird\u2019s-eye view.<\/p>\n

\n\"Stiched<\/a>
\nZooming in on this image of a mouse brain reveals rectangular lines where images were stitched together, with each colored dot representing a specific brain cell type.<\/span>
\nYongsoo Kim<\/a>, CC BY-NC-ND<\/a><\/span>
\n<\/figcaption><\/figure>\n

But building a map of a city, however detailed, is not the same as understanding its rhythm and atmosphere. Likewise, knowing where every cell is located relative to each other doesn\u2019t necessarily tell researchers how they function or interact. Just as important as charting out the landscape of an organ is coming up with a working theory of how it all fits together and performs as a whole. Right now, Kim notes, analysis lags behind technical advances in data collection.<\/p>\n

\u201cIncredibly rich, high-resolution brain mapping presents a great opportunity for neuroscientists to deeply ponder what this new data says about how the brain works,\u201d Kim writes. \u201cThough there are still many unknowns about the brain, these new tools and techniques could help bring them to light.\u201d<\/p>\n

3. Seeing as recognizing<\/h2>\n

Every improvement in technology brings a parallel improvement in the data it collects, both in quality and in quantity. But that data is only useful insofar as researchers are able to analyze it \u2013 high granularity isn\u2019t helpful if those details aren\u2019t appreciable, and high output isn\u2019t beneficial if it\u2019s too overwhelming to organize.<\/p>\n

Automated microscopes, for example, have made it possible to take time-lapse images of cells, resulting in massive amounts of data that require manual sifting. Neuroscientist Jeremy Linsley<\/a> and his team encountered this dilemma in their own work on neurodegenerative disease. They\u2019ve been relying on an army of interns to scour hundreds of thousands of images of neurons and tally each death \u2013 a slow and expensive process.<\/p>\n

\n\"Microscopy<\/a>
\nThese images show living neurons colored green and dead neurons colored yellow.<\/span>
\nJeremy Linsley<\/a>, CC BY-NC-ND<\/a><\/span>
\n<\/figcaption><\/figure>\n

So they turned to artificial intelligence. Researchers can train an AI model to recognize specific patterns by feeding it many sample images, pointing out structures of interest and extrapolating the algorithm to new contexts. Linsley and his team developed a model to distinguish between living and dead neurons<\/a> with greater speed and accuracy than people trained to do the same task. <\/p>\n

They also opened the black box<\/a> of the model to figure out how it was finding dead cells, revealing new signals of neuron death that researchers previously weren\u2019t aware of because they weren\u2019t obvious to the human eye.<\/p>\n

\u201cBy taking out human guesswork, (AI models) increase the reproducibility and speed of research and can help researchers discover new phenomena in images that they would otherwise not have been able to easily recognize,\u201d writes Linsley.<\/p>\n

4. Seeing as appreciating<\/h2>\n

Even before they had the instruments to zoom in on samples, researchers had a tool in their arsenal to study the living world that they still use today: art.<\/p>\n

\n\"Illustration<\/a>
\nThis illustration from Robert Hooke\u2019s \u2018Micrographia\u2019 shows the structure of cells in a cork.<\/span>
\nRobert Hooke\/National Library of Wales via Wikimedia Commons<\/a><\/span>
\n<\/figcaption><\/figure>\n

Centuries ago, scientists and artists examined plants, animals and anatomy through illustration. Sketches of unfamiliar species in their natural environments aided in their classification, and drawings of the human body advanced study of its structure and function. With the help of the printing press, these artistic renderings \u2013 which later included the view under the lenses<\/a> of early microscopes \u2013 popularized scientific knowledge about the natural world.<\/p>\n

Though hand drawings have since given way to advanced imaging techniques and computer models, the legacy of communicating science through art continues. Scientific publications and BioArt competitions<\/a> highlight laboratory images and videos to share the awe and wonder of studying the natural world with the general public. Using visualizations in classrooms and art museums can also promote science literacy by giving students a chance to look through the eye of the microscope as a scientist would.<\/p>\n

Biologist and BioArt Awards judge Chris Curran<\/a> believes that making visible the processes and concepts of science can grant a greater depth of understanding of the natural world necessary to being an informed citizen. <\/p>\n

\u201cThat those images and videos are often beautiful is an added benefit,\u201d she writes.<\/p>\n

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