Snapshots of Life: A Van Gogh Moment for Pancreatic Cancer

Pancreatic Cancer

Credit: Nathan Krah, University of Utah

Last year, Nathan Krah sat down at his microscope to view a thin section of pre-cancerous pancreatic tissue from mice. Krah, an MD/PhD student in the NIH-supported lab of Charles Murtaugh at the University of Utah, Salt Lake City, had stained the tissue with three dyes, each labelling a different target of interest. As Krah leaned forward to look through the viewfinder, he fully expected to see the usual scattershot of color. Instead, he saw enchanting swirls reminiscent of the famous van Gogh painting, The Starry Night.

In this eye-catching image featured in the University of Utah’s 2016 Research as Art exhibition, red indicates a keratin protein found in the cytoskeleton of precancerous cells; green, a cell adhesion protein called E-cadherin; and yellow, areas where both proteins are present. Finally, blue marks the cell nuclei of the abundant immune cells and fibroblasts that have expanded and infiltrated the organ as a tumor is forming. Together, they paint a fascinating new portrait of pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer.

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Creative Minds: A Transcriptional “Periodic Table” of Human Neurons

neuronal cell

Caption: Mouse fibroblasts converted into induced neuronal cells, showing neuronal appendages (red), nuclei (blue) and the neural protein tau (yellow).
Credit: Kristin Baldwin, Scripps Research Institute, La Jolla, CA

Writers have The Elements of Style, chemists have the periodic table, and biomedical researchers could soon have a comprehensive reference on how to make neurons in a dish. Kristin Baldwin of the Scripps Research Institute, La Jolla, CA, has received a 2016 NIH Director’s Pioneer Award to begin drafting an online resource that will provide other researchers the information they need to reprogram mature human skin cells reproducibly into a variety of neurons that closely resemble those found in the brain and nervous system.

These lab-grown neurons could be used to improve our understanding of basic human biology and to develop better models for studying Alzheimer’s disease, autism, and a wide range of other neurological conditions. Such questions have been extremely difficult to explore in mice and other animal models because they have shorter lifespans and different brain structures than humans.

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Snapshots of Life: Wild Outcome from Knocking Out Mobility Proteins

Spiky fibroblast cell

Credit: Praveen Suraneni and Rong Li, Stowers Institute for Medical Research

When biologists disabled proteins critical for cell movement, the result was dramatic. The membrane, normally a smooth surface enveloping the cell, erupted in spiky projections. This image, which is part of the Life: Magnified exhibit, resembles a supernova. Although it looks like it exploded, the cell pictured is still alive.

To create the image, Rong Li and Praveen Suraneni, NIH-funded cell biologists at the Stowers Institute for Medical Research in Kansas City, Missouri, disrupted two proteins essential to movement in fibroblasts—connective tissue cells that are also important for healing wounds. The first, called ARPC3, is a protein in the Arp2/3 complex. Without it, the cell moves more slowly and randomly [1]. Inhibiting the second protein gave this cell its spiky appearance. Called myosin IIA (green in the image), it’s like the cell’s muscle, and it’s critical for movement. The blue color is DNA; the red represents a protein called F-actin.

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Snapshots of Life: Nanotechnology Meets Cell Biology

Photo of four bright yellow spheres on a textured gray surface

Caption: Scanning electron micrograph of silica beads (yellow) on the surface of a human fibroblast cell.
Source: Matthew Ware and Biana Godin Vilentchouk, Houston Methodist Research Institute, Texas

Many of the most exciting frontiers in biomedical research sound like the stuff of science fiction, but here’s some work that even looks like it’s straight from the set of Star Trek! This scanning electron micrograph captures the pivotal moment when nanospheres—a futuristic approach to drug delivery—are swallowed up by a human fibroblast cell.

The NIH-funded researchers who took this stunning photograph, one of the winners in the Federation of American Societies for Experimental Biology’s 2013 BioArt Competition, are using tiny silica beads (yellow in the image above) to investigate how drug-laden nanoparticles are transported into cells. They are focusing on fibroblasts because although they produce vital molecules that give healthy tissue its structure and strength, they also surround and nourish many types of cancer.

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Exploiting Stem Cell Stickiness for Sorting

Photo of purple web-like objects adjacent to photo of a gloved hand holding a clear device with green lines, making it look like a circuit board.

Caption: Adult human fibroblast cells (left) are reprogramed into human induced pluripotent stem cells
(iPS cells). The iPS cells have a characteristic stickiness that lets them to adhere to sorting devices
(right) with different strengths than other cells.
Credit: Ankur Singh and Andres Garcia, Institute for Bioengineering & Bioscience, Georgia Tech

There is much excitement about the potential of stem cells for many applications, including regenerative medicine and treating human diseases. But growing pure cultures of stem cells by reprograming adult cells—like human fibroblasts—into a less differentiated cell type called a human induced Pluripotent Stem cell (iPS cell), is a tricky business. These stem cell cultures are often contaminated with other normal cells that do not have the same coveted therapeutic potential. Manually sorting these stem cells is time consuming and difficult; using chemical approaches can damage the DNA inside. Now, we have a better option: NIH funded researchers from the Georgia Institute of Technology in Atlanta have invented a cell-sorting device that exploits specific characteristics of iPS cells.

iPS cells have a characteristic ‘stickiness’ that allows them to adhere to surfaces inside the sorting chip with different strengths than other cells. This stickiness is due to a signature set of proteins on the surface of these stem cells. Normal cells are coated in other proteins that give their surfaces different adhesive properties.

The researchers say the method is gentle, efficient, rapid, and generates collections of stem cells that are 95–99% pure.

Reference:

Adhesion strength-based, label-free isolation of human pluripotent stem cells. Singh A, Suri S, Lee T, Chilton JM, Cooke MT, Chen W, Fu J, Stice SL, Lu H, McDevitt TC, García AJ. Nat Methods. 2013 May;10(5):438-44.

NIH support: National Institute of General Medical Sciences; National Institute of Neurological Disorders and Stroke; National Cancer Institute