Creative Minds: Teaming Math and Science for an HIV Cure

Alison Hill

Alison Hill

You may have heard about young mathematicians who’ve helped to design cooler cars, smarter phones, and even more successful sports teams. But do you know about the young mathematician who is helping to find a cure for the estimated 35 million people worldwide infected with the human immunodeficiency virus (HIV)? If not, I’d like to introduce you to Alison Hill, a mathematical biologist at Harvard University, Cambridge, MA.

Recognized this year by Forbes Magazine’s 30 Under 30 as one of the most important young innovators in healthcare, Hill is teaming with clinicians to develop sophisticated mathematical tools to predict which experimental drugs might work to clear HIV from the body once and for all. While current treatments are able to reduce some patients’ HIV burden to very low or even undetectable levels, it is eradication of this viral reservoir that stands between such people living with a serious, but controllable chronic disease and actually being cured.

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Bioengineering: Big Potential in Tiny 3D Heart Chambers

iPS human heart

Caption: Heart microchamber generated from human iPS cells; cardiomyocytes (red), myofibroblasts (green), cell nuclei (blue) 
Credit: Zhen Ma, University of California, Berkeley

The adult human heart is about the size of a large fist, divided into four chambers that beat in precise harmony about 100,000 times a day to circulate blood throughout the body. That’s a very dynamic system, and also a very challenging one to study in real-time in the lab. Understanding how the heart forms within developing human embryos is another formidable challenge. So, you can see why researchers are excited by the creation of tiny, 3D heart chambers with the ability to exist (see image above) and even beat (see video below) in a lab dish, or as scientists  say “in vitro.”

iPS heart cells video

Credit: Zhen Ma et al., Nature Communications

To achieve this feat, an NIH-funded team from University of California, Berkeley, and Gladstone Institute of Cardiovascular Disease, San Francisco turned to human induced pluripotent stem (iPS) cell technology. The resulting heart chambers may be miniscule—measuring no more than a couple of hair-widths across—but they hold huge potential for everything from improving understanding of cardiac development to speeding drug toxicity screening.

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Manipulating Microbes: New Toolbox for Better Health?

Bacteroides thetaiotaomicron

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.

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Snapshots of Life: Host vs. Pathogen

Cryptoccocus neoformans

Caption: This scanning electron microscopy image shows mouse macrophages (green) interacting with a fungal cell (blue).
Credit: Sabriya Stukes and Hillary Guzik, Albert Einstein College of Medicine

Macrophages are white blood cells that generally destroy foreign invaders by engulfing them. It’s a tried-and-true strategy, but it doesn’t always work. Cryptoccocus neoformans, a deadly fungal pathogen commonly found in the feces of pigeons, can foil even the best macrophages. No one has captured this grand escape—but researchers are getting a whole lot closer to doing so.

Sabriya Stukes, an NIH-funded microbiologist at New York’s Albert Einstein College of Medicine, studies the interactions between C. neoformans and macrophages to determine how the former causes the lung infection cryptococcosis, which can be deadly for people with compromised immune systems. Stukes believes what makes C. neoformans so dangerous is that it can survive the acid death chamber inside macrophages—a situation that spells doom for most other pathogens. A big reason behind this fungus’s power of survival is its thick coat of polysaccharides, which serves as woolly-looking armor. Once a macrophage engulfs the fungus, this coat can give the white blood cell “indigestion,” prompting it to spit the fungus back into the lungs where it can cause disease.  Continue reading

Creative Minds: Meet a Theoretical Neuroscientist

Sean Escola

Sean Escola

Most neuroscientists make their discoveries in a traditional laboratory or clinical setting. Sean Escola, a theoretical neuroscientist at Columbia University in New York, just needs a powerful computer and, judging from his photo, a good whiteboard.

Using data that he and his colleagues have recorded from living brain cells, called neurons, Escola crunches numbers to develop rigorous statistical models that simulate the activity of neuronal circuits within the brain. He hopes his models will help to build a new neuroscience that brings into sharper focus how the brain’s biocircuitry lights up to generate sensations and thoughts—and how it misfires in various neurological disorders, particularly in mental illnesses.

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