It may surprise you to learn that the poised young woman featured in this video was a sophomore in high school at the time the film was made. Today, Emily Ashkin is a high school senior with impressive laboratory experience and science awards to her name. As it happens, she’s also introducing me when I deliver a keynote address at the Melanoma Research Alliance’s annual scientific meeting — today, here in Washington, D.C.
What struck me most when I heard Emily’s story was her fearlessness. When mentoring young students, helping some to believe in themselves can be a real challenge. Not Emily. She faces her challenges by seeking solutions, asking—as she does in the video—“Why can’t that be me?”
Caption: A decoy protein that mimics the CD4 receptor (red), the CCR5 receptor (green), and a natural antibody (grey), binds to the HIV envelope protein (three white blobs) and blocks it from infecting immune cells.
Credit: Michael Farzan
Over more than a century, researchers have succeeded in developing vaccines to prevent polio, smallpox, cervical cancer, and many other viral diseases. For three decades now, they have tried to design an effective vaccine for the human immunodeficiency virus (HIV) that causes AIDS. Despite plenty of hard work, lots of great science, and some promising advances along the way, an effective traditional vaccine still remains elusive. That has encouraged consideration of alternative approaches to block HIV infection.
Now in the journal Nature , an NIH-funded team reports promising early results with one of these interesting alternatives. The team hypothesized that producing a protein that binds to HIV and prevents it from entering cells might provide protection. So they designed such a protein, and, using an animal model, introduced multiple copies of a gene that makes this protein. In a small study of non-human primates, this gene-therapy approach blocked HIV infection, even when the animals were exposed repeatedly to large doses of the virus.
Today, we hear a great deal about which foods to eat and which to avoid to maintain a healthy body. Though we know that one of the strongest contributors to body weight is heredity, there has been less specific information available about the genetics underlying obesity. But research in this area is progressing at a phenomenal pace, and new genomic discoveries are helping to bring into better focus how our bodies store fat and how the complex interplay of genetics, diet, behavior, and other factors determine whether we can readily maintain a healthy body weight, or whether it takes a lot of work to do so.
Two papers in Nature provide lots of fresh clues into the genetic factors involved in predisposing to obesity. Researchers in the international Genetic Investigation of ANthropometric Traits (GIANT) Consortium, more than 500 strong and including some of the members of my own NIH research lab (including me), examined the genomes of more than half a million people to look for genes and regions of chromosomes that play a role in body fat distribution and obesity. They turned up over 140 genetic locations that, like low-intensity voices in a choir of many, contribute to these traits. Further analyses of the specific genes located in these regions suggest the possibility that the programming behind how fat cells form may influence their distribution, a discovery that could lead to exploitable findings down the road.
Caption: The location and abundance of six proteins—e-cadherin (green), vimentin (blue), actin (red), estrogen receptor, progesterone receptor, and Ki67—found in breast cancer cells are seen in this multiplexed ion beam image. Cells positive for estrogen receptor a, progesterone receptor, and Ki-67 appear yellow; cells expressing estrogen receptor a and the progesterone receptor appear aqua.
Credit: Michael Angelo
The artistic masterpiece above, reminiscent of a stained glass window, is the work of Michael Angelo—no, not the famous 16th Century Italian artist, but a 21st Century physician-scientist who’s out to develop a better way of looking at what’s going on inside solid tumors. Called multiplexed ion beam imaging (MIBI), Angelo’s experimental method may someday give clinicians the power to analyze up to 100 different proteins in a single tumor sample.
In this image, Angelo used MIBI to analyze a human breast tumor sample for nine proteins simultaneously—each protein stained with an antibody tagged with a metal reporter. Six of the nine proteins are illustrated here. The subpopulation of cells that are positive for three proteins often used to guide breast cancer treatment (estrogen receptor a, progesterone receptor, Ki-67) have yellow nuclei, while aqua marks the nuclei of another group of cells that’s positive for only two of the proteins (estrogen receptor a, progesterone receptor). In the membrane and cytoplasmic regions of the cell, red indicates actin, blue indicates vimentin, which is a protein associated with highly aggressive tumors, and the green is E-cadherin, which is expressed at lower levels in rapidly growing tumors than in less aggressive ones. Taken together, such “multi-dimensional” information on the types and amounts of proteins in a patient’s tumor sample may give oncologists a clearer idea of how quickly that tumor is growing and which types of treatments may work best for that particular patient. It also shows dramatically how much heterogeneity is present in a group of breast cancer cells that would have appeared identical by less sophisticated methods.
When Amy Gladfelter arrived at the University of Basel in Switzerland to pursue post-doctoral work in 2001, she remembers that her research interests were still a little up in the air. As she settled into the new lab, Gladfelter remembers watching movies that others had made of the filamentous fungus Ashbya gossypii and wondering how on earth its myriad nuclei could share the same cytoplasm and do different things. Now, more than a decade later, this cell biologist finds herself at Dartmouth College, Hanover, N.H., where she is leading a lab that is making its own thought-provoking movies and pushing the envelope in an effort to answer this and many other scientific questions.
As you’ll learn by watching this video, Gladfelter’s work has implications far beyond the world of fungi because the filamentous proteins called septins, which act to define territory within Ashbya cells, are very similar to certain proteins found in human cells. While such proteins are normally very flexible, they can morph into toxic, solid states in certain human disorders, including Alzheimer’s disease and Huntington’s disease. Besides illustrating the value of Ashbya for uncovering clues to neurodegenerative disorders, this video delivers a broader message about the importance of all kinds of model organisms for efforts to understand our own biology.