systems biology
Lens Crafting
Posted on by Dr. Francis Collins

Credit: Salma Muhammad Al Saai, Salil Lachke, University of Delaware, Newark
Live long enough, and there’s a good chance that you will develop a cataract, a clouding of the eye’s lens that impairs vision. Currently, U.S. eye surgeons perform about 3 million operations a year to swap out those clouded lenses with clear, artificial ones [1]. But wouldn’t it be great if we could develop non-surgical ways of preventing, slowing, or even reversing the growth of cataracts? This image, from the lab of NIH-grantee Salil Lachke at the University of Delaware, Newark, is part of an effort to do just that.
Here you can see the process of lens development at work in a tissue cross-section from an adult mouse. In mice, as in people, a single layer of stem-like epithelial cells (far left, blue/green) gives rise to specialized lens cells (middle, blue/green) throughout life. The new cells initially resemble their progenitor cells, displaying nuclei (blue) and the cytoskeletal protein actin (green). But soon these cells will produce vast amounts of water-soluble proteins, called crystallins, to enhance their transparency, while gradually degrading their nuclei to eliminate light-scattering bulk. What remains are fully differentiated, enucleated, non-replicating lens fiber cells (right, green), which refract light onto the retina at the back of the eye.
Creative Minds: Searching for Solutions to Chronic Infection
Posted on by Dr. Francis Collins
If you or a loved one has ever struggled with a bacterial infection that seemed to have gone away with antibiotic treatment, but then came back again, you’ll probably be interested to learn about the work of Kyle Allison. What sometimes happens when a person has an infection—for instance, a staph infection of the skin—is that antibiotics kill off the vast majority of bacteria, but a small fraction remain alive. After antibiotic treatment ends, those lurking bacterial “persisters” begin to multiply, and the person develops a chronic infection that may be very difficult and costly to eliminate.
Unlike antibiotic-resistant superbugs, bacterial persisters don’t possess any specific genetic mutations that protect them against the killing power of one particular medication or another. Rather, the survival of these bacteria depends upon their ability to enter a dormant state that allows them to hang on in the face of antibiotic treatment. It isn’t clear exactly how the bugs do it, and that’s where Kyle’s work comes in.
Manipulating Microbes: New Toolbox for Better Health?
Posted on by Dr. Francis Collins

Caption: Bacteroides thetaiotaomicron (white) living on mammalian cells in the gut (large pink cells coated in microvilli) and being activated by exogenously added compounds (small green dots) to express specific genes, such as those encoding light-generating luciferase proteins (glowing bacteria).
Credit: Janet Iwasa, Broad Visualization Group, MIT Media Lab
When you think about the cells that make up your body, you probably think about the cells in your skin, blood, heart, and other tissues and organs. But the one-celled microbes that live in and on the human body actually outnumber your own cells by a factor of about 10 to 1. Such microbes are especially abundant in the human gut, where some of them play essential roles in digestion, metabolism, immunity, and maybe even your mood and mental health. You are not just an organism. You are a superorganism!
Now imagine for a moment if the microbes that live inside our guts could be engineered to keep tabs on our health, sounding the alarm if something goes wrong and perhaps even acting to fix the problem. Though that may sound like science fiction, an NIH-funded team from the Massachusetts Institute of Technology (MIT) in Cambridge, MA, is already working to realize this goal. Most recently, they’ve developed a toolbox of genetic parts that make it possible to program precisely one of the most common bacteria found in the human gut—an achievement that provides a foundation for engineering our collection of microbes, or microbiome, in ways that may treat or prevent disease.