Merry Microscopy and a Happy New Technique!

Color EM WreathSeasons Greetings! What looks like a humble wreath actually represents an awe-inspiring gift to biomedical research: a new imaging technique that adds a dash of color to the formerly black-and-white world of electron microscopy (EM). Here the technique is used to visualize the uptake of cell-penetrating peptides (red) by the fluid-filled vesicles (green) of the endosome (gray), a cellular compartment involved in molecular transport. Without the use of color to draw sharp contrasts between the various structures, such details would not be readily visible.

This innovative technique has its origins in a wonderful holiday story. In December 2003, Roger Tsien, a world-renowned researcher at the University of California, San Diego (UCSD), decided to give himself a special present. With the lab phones still and email traffic slow for the holidays, Tsien decided to take advantage of the peace and quiet to spend two weeks alone at the research bench, pursuing an intriguing, yet seemingly wacky, idea. He wanted to find a way to deposit ions of a rare earth metal, called lanthanum, directly into cells as the vital first step in creating a new imaging technique designed to infuse EM with some much-needed color. After the holidays, when the lab returned to its usual hustle and bustle, Tsien handed off his project to Stephen Adams, a research scientist in his lab, thereby setting in motion a nearly 13-year quest to perfect the colorful new mode of EM.

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Summer Reading Suggestions from Scientists: Robert Horvitz

Summer ReadingTwo Science Selections: 

Horace Freeland Judson, Eighth Day of Creation. A comprehensive history of the origins and early science of the field of modern molecular biology, written by historian Horace Freeland Judson based on personal interviews with those who drove the revolution in biology. First and foremost are the science—DNA, RNA and protein, the genetic code, and gene regulation—and the scientific process—the seed ideas, the “aha” insights and the brilliant and elegant experiments. But this book is also the story of scientists in the process of discovery and of how the science that emerged was at least as much a consequence of the personalities as of the experimental skills of those involved. Fascinating, engaging, and fun—I’ve recommended this book to many, scientist and non-scientist alike.

Georgina Ferry, Dorothy Hodgkin. A superb biography of one of modern science’s most exceptional and distinguished pioneers. Awarded the Nobel Prize in Chemistry in 1964 for determining the crystal structures of penicillin and vitamin B12, Dorothy Crowfoot Hodgkin faced repeated challenges as a woman attempting to study and then pursue a career in chemistry in the 1930s and 1940s in England. Hodgkin is only one of four women ever awarded the Nobel Prize in Chemistry; the others were Marie Curie (1911); her daughter Irene Joliot-Curie (1935); and Ada Yonath (2009). Once recognized, Hodgkin worked hard to combat social inequalities and was president for more than a decade of Pugwash, an international organization founded by Bertrand Russell and dedicated to preventing war. Hodgkin has been a role model for many, although she disagreed rather strongly with the political views and actions of her most famous student, Margaret Thatcher.

Personal Connection: 

George Klein, The Atheist and the Holy City. This book was a gift to me from George Klein, a Hungarian-Swedish tumor biologist and virologist at the Karolinska Institute in Stockholm. George and his wife Eva are best known in biological circles for their pioneering discovery of the role of the Epstein-Barr virus in Burkitt’s lymphoma and other neoplasms. This book, one of many George has written, is a compilation of essays that focus on science, but incorporate history, religion and philosophy. Its sections are entitled “The Wisdom and Folly of Scientists,” “Journeys,” “Viruses and Cancer” and “The Human Condition,” and collectively touch upon topics as diverse as DNA hybridization, the discovery of Rous sarcoma virus, and the life cycle of Schistosoma mansoni, as well as the Nazi death camps, scientific creativity, and the conviction that God is an example of man’s wishful thinking. Thought-provoking and uplifting, this book is a story of science and much more. A must read for all.Line

Bob Horvitz

Robert Horvitz
Credit: Aynsley Floyd/ AP Images for HHMI

Robert Horvitz, Ph.D. is the David H. Koch Professor of Biology at the Massachusetts Institute of Technology, and a member of the MIT McGovern Institute for Brain Research and the MIT Koch Institute for Integrative Cancer Research. Dr. Horvitz is co-winner of the 2002 Nobel Prize in Physiology or Medicine for discoveries concerning genetic regulation of organ development and programmed cell death.

Summer Reading Suggestions from Scientists: Harold Varmus

Summer ReadingSummertime! Long weekends, a vacation, the threat of boredom. Time for uninterrupted reading—on beaches or in air-conditioned bedrooms. A chance to look beyond the best-seller lists or the daily news to dive, with full concentration, into one or two books that some friend has argued might be a life-changing experience. In that spirit, here are two for which I would make that argument to almost any friend.

In the sphere of science: The Age of Wonder: The Romantic Generation and the Discovery of the Beauty and Terror of Science, by Richard Holmes (HarperCollins, 2008). Holmes is primarily a literary biographer (of Coleridge and other Romantic poets), but also an art historian and a science junkie, who has written about ballooning and women scientists. Of the many books I’ve read about the growth of the scientific enterprise, The Age of Wonder stands out for several reasons: its deep engagement with the full range of cultural and political currents in which science arises; its focus on the excitement about discovery—geographical, astronomical, chemical, biological—that permeated the late 18th and early 19th centuries; and its absorption with personal histories of people who made those discoveries. Holmes is a superb storyteller and drawn to the complexities of life (especially in Britain) that influenced the talented people—Joseph Banks, Humphry Davy, several members of the Herschel family—who made novel observations that changed our perceptions of the world and solidified the place of science.

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Summer Reading Suggestions from Scientists

Summer ReadingNow that we are in the “dog days” of summer, it’s time again to consider which books to pack (or load onto your e-reader) for your well-deserved getaway to the beach and beyond. With so many interesting titles published every year, it’s never easy to make recommendations. But I thought it might be fun to ask a few distinguished researchers to share a few of their favorite reads—both about science and other things in the world at large. Some might be classics; some might have just been published. It’s up to the guests to decide.

During the month of August, the NIH Director’s Blog will run a series of guest posts in which some of biomedical science’s most creative minds discuss one or two of the books they’ve been reading. I’m sure what they share will be informative, provocative, and possibly even provide you with a few more possibilities for your late summer reading list. So, please check out the blog next Tuesday for the first installment in our scientists’ summer reading series, which happens to be penned by an avid reader who also holds a Nobel Prize in Physiology or Medicine. Can anyone guess who it is?

Cool Videos: Pushing the Limits of Live-Cell Microscopy

Actin

If you’re not watching recent work in biology, you might have thought that light microscopy hit its limits years ago.  After all, it’s been around a long time. But to the contrary, microscopic imaging technology just keeps getting better and better. Here you can look with unprecedented clarity at just one of the many dynamic processes going on within a living cell. Specifically, this video shows actin fibers (orange-red), which are key components of the cell’s cytoskeleton, slowly pulling clathrin-coated pits (green), which are basket-like structures containing molecular cargo, away from the cell’s external membrane and deeper within the cell.

This remarkable live-action view was produced using one of two new forms of extended-resolution, structured illumination microscopy (SIM). SIM is faster than other forms of super-resolution fluorescence microscopy. It’s also less damaging to cells, making it the go-to method for live-cell imaging. The downside has been SIM’s limited resolution—just twice that of conventional light microscopes. However, Nobel Prize-winner Eric Betzig and postdoc Dong Li of Howard Hughes Medical Institute, Janelia Research Campus, Ashburn, VA, along with colleagues including Jordan Beach and John Hammer at NIH’s National Heart, Lung, and Blood Institute, recently came up with two different solutions to enhance SIM’s spatial resolution.

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