Caption: MEMOIR cells variably activated (cyan). The recorded information is then read out to visualize certain RNA transcripts (red). Credit: Elowitz and Cai Labs/Caltech
One of the most fascinating challenges in biology is understanding how a single cell divides and differentiates to form a complex, multicellular organism. Scientists can learn a lot about this process by tracking time-lapse images through a microscope. But gazing through a lens has its limitations, especially in the brain and other opaque and inaccessible tissues and organs.
With support from a 2017 NIH Director’s Transformative Research Program, a California Institute of Technology (Caltech) team now has a way around this problem. Rather than watching or digging information out of cells, the team has learned how to program cells to write their own molecular memoirs. These cells store the information right in their own genomic hard drives. Even better, that information is barcoded, allowing researchers to read it out of the cells without dissecting tissue. The programming can be performed in many different cell types, including stem or adult cells in tissues throughout the body.
Caption: University of Washington team that developed new light-sheet microscope (center) includes (l-r) Jonathan Liu, Adam Glaser, Larry True, Nicholas Reder, and Ye Chen. Credit: Mark Stone/University of Washington
After surgically removing a tumor from a cancer patient, doctors like to send off some of the tissue for evaluation by a pathologist to get a better idea of whether the margins are cancer free and to guide further treatment decisions. But for technical reasons, completing the pathology report can take days, much to the frustration of patients and their families. Sometimes the results even require an additional surgical procedure.
Now, NIH-funded researchers have developed a groundbreaking new microscope to help perform the pathology in minutes, not days. How’s that possible? The device works like a scanner for tissues, using a thin sheet of light to capture a series of thin cross sections within a tumor specimen without having to section it with a knife, as is done with conventional pathology. The rapidly acquired 2D “optical sections” are processed by a computer that assembles them into a high-resolution 3D image for immediate analysis.
Credit: Michael Shribak, Marine Biological Laboratory, Woods Hole, MA
Birds do it, bees do it, and even educated fleas do it. No, not fall in love, as the late Ella Fitzgerald so famously sang. Birds and insects can see polarized light—that is, light waves transmitted in a single directional plane—in ways that provides them with a far more colorful and detailed view of the world than is possible with the human eye.
Still, thanks to innovations in microscope technology, scientists have been able to tap into the power of polarized light vision to explore the inner workings of many complex biological systems, including the brain. In this image, researchers used a recently developed polarized light microscope to trace the spatial orientation of neurons in a thin section of the mouse midbrain. Neurons that stretch horizontally appear green, while those oriented at a 45-degree angle are pinkish-red and those at 225 degrees are purplish-blue. What’s amazing is that these colors don’t involve staining or tagging the cells with fluorescent markers: the colors are generated strictly from the light interacting with the physical orientation of each neuron.
Credit: Zhang, Y.V., Aikin, T.J., Li, Z., and Montell, C., University of California, Santa Barbara
It’s a problem that parents know all too well: a child won’t eat because their oatmeal is too slimy or a slice of apple is too hard. Is the kid just being finicky? Or is there a biological basis for disliking food based on its texture? This image, showing the tongue (red) of a fruit fly (Drosophila melanogaster), provides some of the first evidence that biology could indeed play a role .
The image shows a newly discovered mechanosensory nerve cell (green), which is called md-L, short for multidendritic neuron in the labellum. When the fly extends its tongue to eat, the hair bristles (short red lines) on its surface bend in proportion to the consistency of the food. If a bristle is bent hard enough, the force is detected at its base by one of the arms of an md-L neuron. In response, the arm shoots off an electrical signal that’s relayed to the central part of the neuron and onward to the brain via the outgoing informational arm, or axon.
Cell biologists now possess an unprecedented set of laboratory tools to look inside living cells and study their inner workings. Many of these tools have only recently appeared, while others have deeper historical roots. Combining the best of the old with the best of the new, researchers now have the power to explore the biological underpinnings of life in ways never seen before.
That’s the story of this video from the lab of Roberto Weigert, an intramural researcher with NIH’s National Cancer Institute and National Institute of Dental and Craniofacial Research. Weigert is a cell biologist who specializes in intravital microscopy (IVM), an extremely high-resolution imaging tool that traces its origins to the 19th century. What’s unique about IVM is its phenomenal resolution can be used in living animals, allowing researchers to watch biological processes unfold in organs under real physiological conditions and in real time.