Recreating a Home for Gut Parasites Is Really Hard

Single-cell organisms like Giardia attach to the small intestines to take nutrients, but how they do so is still something of a mystery.

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Dec 8 2014, 12:45pm

Giardia. ​Image: ​Centers for Disease Control

Giardiasis—or beaver fever—is just one of the many illnesses that you can pick up from unclean water. It's caused by the parasite Giardia lamblia, which waits until it makes it through your stomach and into your small intestine before causing an infection that leads to diahrrea and bowel irritation.

Though not as fatal as cholera (most infections clear in about a month), Giardia inf​ects about a third of all people in developing countries and up to 10 percent of people globally, according to the ​Centers for Disease Control and Prevention.

Scientists don't fully understand how Giardia works—specifically how it swims through intestinal mucus and attaches to our cell walls.

Heidi Elme​ndorf, a biologist at Georgetown Universit​y, wants to understand these processes better, and hopefully develop more targeted drugs to fight infections in the future. She's teamed up with the Institute f​or Soft Matter Synthesis and Metrology, a product of the physics department at Georgetown, to use a rare machine that acts as both a microscope and a ​rheometer to simulate the mucus in the intestinal tract.

Image: Courtesy Heidi Elmendorf and her lab

MOTHERBOARD: How did you become interested in parasites like Giardia?
Heidi Elmendorf: I think I like parasites so much because a lot of what they do is so different from how an introductory biology textbook tells you how cells do things. Intro textbooks give you the norm, and parasites just haven't read that book yet.

I was looking for a new parasite after I studied malaria for my graduate work, and I found this beautiful cell—Giardia. It's actually this incredibly complicated, stunningly beautiful kind of cell. It's hard to remember that it's just one because it's just got such a complicated structure.

I also like it because it qualifies as what we call a "neglected tropical disease." They're diseases that we haven't traditionally paid as much attention to—HIV, malaria and TB are the big three, but everything else becomes "another disease," they're not even named. But these neglected diseases actually have a huge impact on human health, primarily because they're so prevalent.

It was appealing to me to study something that wasn't getting a lot of attention but was a very serious health problem around the world, particularly for children.

What's some of the work your lab is studying now?
​We're interested in how Giardia actually sets up an infection inside the intestine, and how it interacts with your mucus in your intestinal tract. All intestinal pathogens either have to invade the cells or attach to them; otherwise peristalsis (the natural movement of your intestines as they push food through) will flush them through the system.

Mucus itself is very disgusting or very fascinating, depending on your point of view

What makes this work so challenging?
For starters, the nature of mucus. Mucus itself is very disgusting or very fascinating, depending on your point of view. All surfaces in the human body that aren't covered with skin where you have the fresh surface of cells exposed are covered with mucus, like your nose, eyes, lungs and intestines.

A lot of things are either a liquid or a gel, but whatever you do to them doesn't change their properties. Mucus, as it turns out, behaves as if it's a ​non-Newtonian fluid. It's like a gel, and when you exert force on it, you change the consistency of the material—that's why you can sneeze it out of your nose.

Giardia, we know, exerts forces on it. It's a swimmer—it has eight flagella, we know it swims around, and we know that when Giardia interacts with mucus it changes how it behaves … From a biophysics perspective, it's a very complicated material that's not well understood.

The other challenge is that we're studying cells. They're really small, and the process we're looking at happens very quickly. It's not impossible, but it makes it technically challenging.

How do you overcome these challenges?
We got really lucky that we had the right guys next door. Though I'm the one that got this work going, my graduate student Theodore Picou and Jeff Ur​bach, a physicist from Georgetown, are also working on the project. Urbach has a swanky microscope that lets us do all the imaging.

Giardia. Image: ​schmidty4112/Flickr​

The microscope actually does two things: it's both a microscope, and also a rheometer, which means we have some kind of variability. Normally, we have microscope slides and cover slips, but that's a very stationary kind of observation. But we want to study Giardia in its intestinal tract—where it spends most of its daily life. If you think instead of putting your sample on the slide, but then spin your cover slip around, you're going to generate what we call sheer forces. Basically you're going to spin the fluid underneath it as well. It's more similar to reality.

It also has this incredibly fast imaging capability. We need to capture thousands of images with even just a short clip. When people talk about 'big data' they seem to be thinking of what millions of people are doing, or millions of web pages, but what we think of big data is 10 seconds of video of a single parasite. It can actually take us a couple of days to process those images through the unique algorithms we're using to look at what's happening to the parasite and the environment around it.

So, studying parasites like Giardia is biology with a touch of physics and computer science?
Right—it's clearly a question of biological organisms and substances, which is where I come in. But it's also a question of hydrodynamics, or fluid flow, and that's an important set of principles we use in terms of attachment. And then part of the work is in this newly emerging field called soft matter, where materials like mucus behave as neither solids nor liquids that bring in physicists and chemists. This challenge isn't unique to our research—a lot of fascinating research happens at the intersection of disciplines.

Is there anything else your lab is working on?
In addition to our work figuring out how Giardia attaches, we're looking for ways to clear the infection. We have a patient on a class of drugs already, in our first drug target block attachment. In theory, you can stop an infection. The next step in the research is to test things on mice.

I have a graduate student, Sweta Batni, who's doing a meta-analysis about giardiasis trying to better understand consequences from human health that giardiasis causes. What she's found is a correlation between Giardia and malnutrition. Consistently, infection with Giardia, particularly in children, impacts children's nutritional status, and this can be measured in terms of their growth. It kind of makes sense, and it's striking that it took so long for it to come out.