Creative Minds: Mapping Molecules in their Cellular Compartments

Alice Ting

Alice Ting, Ph.D.
Credit: Vilcek Foundation

If you were trying to understand how a city functions, it would be useful to map not only its streets and buildings, but to identify all of the people in the city and pinpoint their locations at different times throughout the day. That’s pretty much what biologists would like to do for a cell: map an entire living cell in a way that identifies all of its parts and shows their precise locations at various points in time.

The challenge has been developing the tools and technologies needed to create such a map. Among those who have risen to that challenge is Alice Ting, an associate professor at the Massachusetts Institute of Technology (MIT), Cambridge, MA, and winner of a 2008 NIH Director’s Pioneer Award and a 2013 NIH Director’s Transformative Research Award.

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Snapshots of Life: Fisheye View

Goldfish retina

Credit: Bryan William Jones and Robert E. Marc, University of Utah, Salt Lake City

It looks like a celebration with confetti and streamers that the photographers—among the winners of the Federation of American Societies for Experimental Biology’s 2013 BioArt Competition—captured in this image. But these dots and lines are actually cells in the retina of a goldfish. And what such images reveal may be far more than just a pretty picture.

NIH-funded researchers at the University of Utah used a set of tools called Computational Molecular Phenotyping (CMP) to take a snapshot of the amacrine cells in the retina. The retina is delicate, light-sensitive tissue in the back of the eye, and its amacrine cells are involved in processing and conveying signals from the light-gathering photoreceptor cells to the brain’s visual cortex, where the image is decoded. The colors in this photograph reveal the unique metabolic chemistry, and thus the identity, of each subtype of neuron. The red, yellow, and orange cells are amacrine neurons with a high level of the amino acid glycine; the blue ones have a lot of the neurotransmitter gamma-aminobutyric acid (GABA). The green color tells us something different: it provides a physiological snapshot revealing which neurons were active and talking to each other at the time the image was created.

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Creative Minds: REST-ling with Alzheimer’s Disease

REST in healthy and Alzheimer's cells

Caption: The REST protein (green) is dormant in young people but switches on in the nucleus of normal aging human neurons (top), apparently providing protection against age-related stresses, including abnormal proteins associated with neurodegenerative diseases. REST is lost in neuron nuclei in critical brain regions in the early stages of Alzheimer’s disease (bottom). Neurons are labeled with red.
Credit: Yankner Lab, Harvard Medical School

Why do some people remain mentally sharp over their entire lifetimes, while others develop devastating neurodegenerative diseases that destroy their minds and rob them of their memories? What factors protect the human brain as it ages? And can what we learn about those factors enable us to find ways of helping the millions of people at risk for Alzheimer’s disease and other forms of senile dementia?

Those are just a few of the tough questions that Bruce Yankner, a 2010 recipient of the NIH Director’s Pioneer Award, has set out to answer by monitoring how gene activity in the brain’s prefrontal cortex (PFC) changes as we age. The PFC is the region of the brain involved in decision-making, abstract thinking, working memory, and many other higher cognitive functions; it is also among the regions hardest hit by Alzheimer’s disease.

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Antimicrobial Resistance: Seeing the Problem at Hand

A hand with green and brown swirls with some orange specks throughout

Credit: Lydia-Marie Joubert, Stanford University Medical Center

You’ll be relieved to know that this is not a real hand, swarming with exotic species of microbes. But this eerie image does send a somber message: antimicrobial resistant bacteria (green) are becoming more common and more resilient, while the numbers of vulnerable bacteria (red) are dwindling.

The artist is Lydia-Marie Joubert, an electron microscopy expert at Stanford University Medical Center. She created this image by overlaying a photograph of artist Francis Hewlett’s sculpture of a human hand, five feet tall and emerging from the grounds of a garden in Wales, with epifluorescence micrographs of Pseudomonas bacteria growing on the surface of a glass tube. Her imaginative image earned her the People’s Choice award from The International Science & Engineering Visualization Challenge, run annually by Science magazine and the National Science Foundation.

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Creative Minds: Making Sense of Stress and the Brain

Photo of a woman in front of a chalk board

Amy Arnsten
Credit: Terry Dagradi, Yale School of Medicine

Right behind your forehead lies the most recently evolved region of the human brain: the prefrontal cortex (PFC). It’s a major control center for abstract thinking, thought analysis, working memory, planning, decision making, regulating emotions, and many of the things we most strongly associate with being human. But in times of stress, the PFC is literally taken offline, allowing more primitive parts of the brain to take over.

Amy Arnsten, a neuroscientist at the Yale School of Medicine, New Haven, CT, has pioneered the study of stress on the brain [1] and how impaired regulation of stress response in the PFC contributes to neurological disorders, such as Attention Deficit Hyperactivity Disorder (ADHD), schizophrenia [2, 3], and Alzheimer’s disease [4]. In these disorders, cells in the PFC are negatively affected, while those in the primary sensory cortex, a more primitive part of the brain that processes vision and sound, are thought to remain relatively unscathed. With support from a 2013 NIH Director’s Pioneer Award, Arnsten hopes to uncover why the PFC is more vulnerable to disease than the primary sensory cortex—and how we might be able to prevent or reverse damage to these circuits.

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