Snapshots of Life: Development in Exquisite Detail

Developmental biology

Credit: Shachi Bhatt and Paul Trainor, Stowers Institute for Medical Research, Kansas City, MO

If you’ve ever tried to take photos of wiggly kids, you know that it usually takes several attempts before you get the perfect shot. It’s often the same for biomedical researchers when taking images with microscopes because there are so many variables—from sample preparation to instrument calibration—to take into account. Still, there are always exceptions where everything comes together just right, and you are looking at one of them! On her first try at using a confocal microscope to image this cross-section of a mouse embryo’s torso, postdoc Shachi Bhatt captured a gem of an image that sheds new light on mammalian development.

Bhatt, who works in the NIH-supported lab of Paul Trainor at the Stowers Institute for Medical Research, Kansas City, MO, produced this micrograph as part of a quest to understand the striking parallels seen between the development of the nervous system and the vascular system in mammals. Fluorescent markers were used to label proteins uniquely expressed in each type of tissue: reddish-orange delineates developing nerve cells; gray highlights developing blood vessels; and yellow shows where the nerve cells and blood vessels overlap.

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Snapshots of Life: Green Eggs and Heart Valves

three-day old chicken embryo

Credit: Jessica Ryvlin, Stephanie Lindsey, and Jonathan Butcher, Cornell University, Ithaca, NY

What might appear in this picture to be an exotic, green glow worm served up on a collard leaf actually comes from something we all know well: an egg. It’s a 3-day-old chicken embryo that’s been carefully removed from its shell, placed in a special nutrient-rich bath to keep it alive, and then photographed through a customized stereo microscope. In the middle of the image, just above the blood vessels branching upward, you can see the outline of a transparent, developing eye. Directly to the left is the embryonic heart, which at this early stage is just a looped tube not yet with valves or pumping chambers.

Developing chicks are one of the most user-friendly models for studying normal and abnormal heart development. Human and chick hearts have a lot in common structurally, with four chambers and four valves pumping two circulations of blood in parallel. Unlike mammalian embryos tucked away in the womb, researchers have free range to study the chick heart in or out of the egg as it develops from a simple looped tube to a four-chambered organ.

Jonathan Butcher and his NIH-supported research group at Cornell University, Ithaca, NY, snapped this photo, a winner in the Federation of American Societies for Experimental Biology’s 2015 BioArt competition, to monitor differences in blood flow through the developing chick heart. You can get a sense of these differences by the varying intensities of green fluorescence in the blood vessels. The Butcher lab is interested in understanding how the force of the blood flow triggers the switching on and off of genes responsible for making functional heart valves. Although the four valves aren’t yet visible in this image, they will soon elongate into flap-like structures that open and close to begin regulating the normal flow of blood through the heart.

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Creative Minds: Fighting Cancer with Supercomputers

Amanda Randles

Amanda Randles

After graduating college with degrees in physics and computer science, Amanda Randles landed her dream first job. She joined IBM in 2005 to work on its Blue Gene Project, which had just unveiled the world’s fastest supercomputer. So fast, in fact, it’s said that a scientist with a calculator would have to work nonstop for 177,000 years to perform the operations that Blue Gene could complete in one second. As a member of the applications team, Randles was charged with writing new code to make the next model run even faster.

Randles left IBM in 2009 for graduate school, with the goal to apply her supercomputing expertise to biomedical research. She spent the next several years developing the necessary algorithms to produce a high-resolution 3D model of the human cardiovascular system, complete with realistic blood flow. Now, an assistant professor at Duke University, Durham, NC, and a 2014 NIH Director’s Early Independence awardee, Randles will build on her earlier work to attempt something even more challenging: simulating the movement of cancer cells through the circulation to predict where a tumor is most likely to spread. Randles hopes all of her late nights writing code will one day lead to software that helps doctors stage cancer more precisely and gives patients accurate personalized computer simulations that put an earlier, potentially life-saving bullseye on secondary tumors.

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Nanoparticles Target Damaged Blood Vessels

Microscopic view of damaged vs. undamaged lamina

Caption: [A] Elastin stain (black) showing damaged elastic lamina in aorta. Inset (higher magnification) shows fluorescent nanoparticles attached to aorta where elastin is damaged. [B] Elastin stain showing aorta with undamaged elastic lamina. Inset shows no nanoparticle attachment. L stands for lumen, the open area inside the aorta.
Credit: Naren Vyavahare, Clemson University

Cardiovascular disease (CVD) is the number one killer of Americans. There are, in fact, many types of CVD—but common to most of them is damaged blood vessels. Stents can be inserted to prop open collapsed or narrowed arteries, and deliver drugs inside vessels. But, so far, we haven’t been able to repair the damaged vessels themselves. Researchers in an NIH-funded team of bioengineers at Clemson University, in South Carolina, are among those who believe that delivering drugs directly to the site of damage to mend the vessel might boost our ability to treat CVDs. And they’ve devised a way to deliver such drugs right where they want them: using specially-crafted nanoparticles.

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Reprograming Adult Cells to Produce Blood Vessels

Green mesh with blue dots over a thick red mesh

Caption: New network of blood vessels (green) grown from reprogrammed adult human cells (blue: connective tissue, red: red blood cells)
Credit: Reproduced from R. Samuel et al, Proc Natl Acad Sci U S A. 2013;110:12774-9.

Individuals with heart disease, diabetes, and non-healing ulcers (which can lead to amputation) could all benefit greatly from new blood vessels to replace those that are diseased, damaged, or blocked. But engineering new blood vessels hasn’t yet been possible. Although we’ve learned how to reprogram human skin cells or white blood cells into so-called induced pluripotent stem (iPS) cells—which have the potential to develop into different cell types—we haven’t really had the right recipe to nudge those cells down a path toward blood vessel development.

But now NIH-funded researchers at Massachusetts General Hospital in Boston have taken another step in that direction. Continue reading