Posted by: salamandercandy | January 28, 2007

What’s so fascinating about antimicrobial peptides?

I study genes that code for antimicrobial peptides, or AMPs. What are these AMPs, and why are they so interesting that I would spend 5-6 precious years of young adulthood doing research on them?

A peptide is a small protein molecule. Yes, protein, just like it says on the nutrition label on your bag of beef jerky. An antimicrobial peptide is able to kill bacteria and other germs by poking holes in the germ’s cell membrane. All animals, even humans, produce AMPs, and they seem to be pretty widespread among plants and other eukaryotes, too. Most people I talk to can understand the potential application of an antimicrobial substance. We all like to be able to kill germs at times, since otherwise they are liable to kill us. The development of antibiotics has been a medical miracle, but we’re living on borrowed time, since many bacteria species are rapidly evolving resistance to whatever antibiotics we throw at them. We will soon need a whole new arsenal. Are AMPs the solution? Well, maybe. There are a lot of practical issues involved in actually using them as medicine. If you swallowed them, these small protein molecules would suffer the same fate as your beef jerky: get digested. But maybe someone can design a new antibiotic based on an AMP molecule but without the easily breakable peptide bonds…

There’s a conservation angle, too. As we’ve discussed at SC several times before, infectious diseases can threaten wildlife. It’s important to understand the genetic basis for immunity in lots of species, so they can be managed to ensure that they have sufficient genetic variation to resist disease threats. In other words, if there are several variants of an immune system gene, don’t let one variant get fixed in the species, because a new disease might come along that can overcome that variant. In reality, of course, humans are only willing to spend so much effort to monitor and manage wildlife. Some charismatic megafauna receive special help through captive breeding programs that might incorporate data on immunity genes. The fates of most species, though, will not be much affected by how much we know about variation in disease resistance among individuals. So, while I hope that conservationists will be able to use my research results, there’s only a small chance that what I do will make a direct difference to endangered animals. A larger, indirect effect might be through education. If more people learn about amazing and potentially useful molecules like AMPs, they might be less willing to extirpate endangered species and the AMPs they produce.

The main reason I study AMPs is because they are a terrific model system for discovering how adaptive evolution occurs at the molecular level. Moreso than for most other genes, AMP evolution is rapid and frequently driven by positive natural selection. In other words, new variants are always appearing that confer higher fitness to the organism, and these replace the old variants. Why this happens isn’t entirely clear, but it could be that germs quickly evolve resistance to a particular AMP, prompting the evolution of a new one in an endless molecular dance. It’s easy to measure the antimicrobial abilities of different AMPs in the lab, and this functional data can be integrated with observations of evolutionary patterns. Adaptive evolution is the reason we are who we are and nature is the way it is. I want to use AMPs to help figure out how the whole process works. And then, who knows? The beauty of basic research, which often goes unappreciated, is that you can never tell what applications your results might lead to. Could Watson and Crick have predicted that their basic research on an obscure acid would lead to genetic counseling? If we learn enough about the fundamental forces of our world, such as natural selection, we’ll be able to move forward in ways currently unimaginable.


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