The Race To Map The Human Body — One Cell At A Time

After the news of an accident in a French drug trial on Friday, you might be wondering what drug trials entail. Here’s a summary sheet on the drug discovery process to clear things up! http://wp.me/p4aPLT-1EZ

Neural Pathways by Alexey Kashpersky

TODAY IN SCIENCE: Ada Lovelace Day

Ada Lovelace Day is an international celebration of the achievements of women in science, technology, engineering, math, and all related STEM fields.

The celebration is named in honor of English mathematician Augusta Ada King (1815-1852), Countess of Lovelace, known colloquially as Ada Lovelace. Lovelace, the daughter of Lord Byron, is sometimes considered the world’s first computer programmer for the algorithm she wrote for Charles Babbage’s analytical engine, one of the world’s first mechanical computers. Over the years there have been historical disagreements over the extent of Lovelace’s knowledge of the subject and the originality of the work she published in her article, “Sketch of the Analytical Engine, with Notes from the Translator,“ but Babbage himself seemed to dismiss such future claims in his memoir.

Check out the collection Science NetLinks put together for Women’s History Month for related resources to help all students understand the role women historically have played in the history of STEM development and those they play in current STEM fields.

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Image Credit: Alfred Edward Chalon [Public domain], via Wikimedia Commons

Got a chemistry-themed watch for Christmas - good for checking the time periodically 😃

This massive virus with its own immune system could hold the future of medicine

French researchers think they’ve found a giant virus big enough to house its own virus-killing devices using a system like CRISPR, and it could be a completely new form of life.

Called a mimivirus, it was first found growing in amoebae in a water tower. At four times the size of a typical virus, you can even see it under a light microscope

When the mimivirus encounters another virus, it stores some of the invader’s genetic material. That way, when it encounters the same kind of virus again, the MIMIVIRE system goes into gene-editing berserker mode, finding the key genes of the virus and cutting them to inert oblivion. This could have major applications.

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The 2016 Nobel Prize in Chemistry is awarded to Jean-Pierre Sauvage, Sir Fraser Stoddart, and Bernard Feringa for the design and production of molecular machines with controllable movements: bit.ly/NobelSci2016

(Image caption: A new technique called magnified analysis of proteome (MAP), developed at MIT, allows researchers to peer at molecules within cells or take a wider view of the long-range connections between neurons. Credit: Courtesy of the researchers)

Imaging the brain at multiple size scales

MIT researchers have developed a new technique for imaging brain tissue at multiple scales, allowing them to peer at molecules within cells or take a wider view of the long-range connections between neurons.

This technique, known as magnified analysis of proteome (MAP), should help scientists in their ongoing efforts to chart the connectivity and functions of neurons in the human brain, says Kwanghun Chung, the Samuel A. Goldblith Assistant Professor in the Departments of Chemical Engineering and Brain and Cognitive Sciences, and a member of MIT’s Institute for Medical Engineering and Science (IMES) and Picower Institute for Learning and Memory.

“We use a chemical process to make the whole brain size-adjustable, while preserving pretty much everything. We preserve the proteome (the collection of proteins found in a biological sample), we preserve nanoscopic details, and we also preserve brain-wide connectivity,” says Chung, the senior author of a paper describing the method in the July 25 issue of Nature Biotechnology.

The researchers also showed that the technique is applicable to other organs such as the heart, lungs, liver, and kidneys.

The paper’s lead authors are postdoc Taeyun Ku, graduate student Justin Swaney, and visiting scholar Jeong-Yoon Park.

Multiscale imaging

The new MAP technique builds on a tissue transformation method known as CLARITY, which Chung developed as a postdoc at Stanford University. CLARITY preserves cells and molecules in brain tissue and makes them transparent so the molecules inside the cell can be imaged in 3-D. In the new study, Chung sought a way to image the brain at multiple scales, within the same tissue sample.

“There is no effective technology that allows you to obtain this multilevel detail, from brain region connectivity all the way down to subcellular details, plus molecular information,” he says.

To achieve that, the researchers developed a method to reversibly expand tissue samples in a way that preserves nearly all of the proteins within the cells. Those proteins can then be labeled with fluorescent molecules and imaged.

The technique relies on flooding the brain tissue with acrylamide polymers, which can form a dense gel. In this case, the gel is 10 times denser than the one used for the CLARITY technique, which gives the sample much more stability. This stability allows the researchers to denature and dissociate the proteins inside the cells without destroying the structural integrity of the tissue sample.

Before denaturing the proteins, the researchers attach them to the gel using formaldehyde, as Chung did in the CLARITY method. Once the proteins are attached and denatured, the gel expands the tissue sample to four or five times its original size.

“It is reversible and you can do it many times,” Chung says. “You can then use off-the-shelf molecular markers like antibodies to label and visualize the distribution of all these preserved biomolecules.”

There are hundreds of thousands of commercially available antibodies that can be used to fluorescently tag specific proteins. In this study, the researchers imaged neuronal structures such as axons and synapses by labeling proteins found in those structures, and they also labeled proteins that allow them to distinguish neurons from glial cells.

“We can use these antibodies to visualize any target structures or molecules,” Chung says. “We can visualize different neuron types and their projections to see their connectivity. We can also visualize signaling molecules or functionally important proteins.”

High resolution

Once the tissue is expanded, the researchers can use any of several common microscopes to obtain images with a resolution as high as 60 nanometers — much better than the usual 200 to 250-nanometer limit of light microscopes, which are constrained by the wavelength of visible light. The researchers also demonstrated that this approach works with relatively large tissue samples, up to 2 millimeters thick.

“This is, as far as I know, the first demonstration of super-resolution proteomic imaging of millimeter-scale samples,” Chung says.

“This is an exciting advance for brain mapping, a technique that reveals the molecular and connectional architecture of the brain with unprecedented detail,” says Sebastian Seung, a professor of computer science at the Princeton Neuroscience Institute, who was not involved in the research.

Currently, efforts to map the connections of the human brain rely on electron microscopy, but Chung and colleagues demonstrated that the higher-resolution MAP imaging technique can trace those connections more accurately.

Chung’s lab is now working on speeding up the imaging and the image processing, which is challenging because there is so much data generated from imaging the expanded tissue samples.

“It’s already easier than other techniques because the process is really simple and you can use off-the-shelf molecular markers, but we are trying to make it even simpler,” Chung says.

Trillion-Ton Iceberg Breaks Off Antarctica

Even though the towering berg weighs more than 1.1 trillion tons (1 trillion metric tons), it won't have a direct impact on sea-level rise. That's because the ice was already floating on the sea. Even so, when an iceberg like this one calves, it can speed up the collapse of the rest of the ice shelf.

One of the largest icebergs ever recorded, packing about a trillion tons of ice or enough to fill up two Lake Eries, has just split off from Antarctica, in a much anticipated, though not celebrated, calving event.

A section of the Larsen C ice shelf with an area of 2,240 square miles (5,800 square kilometers) finally broke away some time between July 10 and today (July 12), scientists with the U.K.-based MIDAS Project, an Antarctic research group, reported today.

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How Vera Rubin discovered dark matter

This famous astronomer carved herself a well-deserved place in history, so why doesn’t the Nobel committee see it that way?

R.I.P. Vera Rubin; 1928-2016.

She never did win the Nobel prize for her discovery.

Original illustrations from the 1851 edition of the Iconographic Encyclopedia of Science, Literature and Art by J.G. Heck.