He’s A Rebel! Paul Heideman visits Lehigh

     This week the Schneider lab had the pleasure of hosting one of our scienImagece heroes, Paul Heideman from The College of William and Mary. He doesn’t wear a leather jacket or anything, and in fact, he looks like a typical white-guy professor. We’re still wondering exactly how he left us so inspired and energized, like we just discovered the thrill of science all over again.

He’s a loner, Dottie, a rebel

     Like most of us, Paul came up the ranks when everyone was advised to learn super cool state-of-the-art molecular techniques, to work on conditional knock-out/knock-in-optogenetic-whatever-the-hell mice, and to focus on cellular mechanism. Did he do this? No. Is he tenured? Yes. Is he funded? Yes, well funded. Is he happy? He seems pretty darn ecstatic.

     Second, he studies the one thing that most biologists avoid like the plague: Individual differences. Most scientists seek to minimize them. They like groups that show little natural variance, and they omit outliers.

      Hating individual differences makes sense in a way. When a drug works to reduce pain or fight infection, you want it to do so reliably in just about everyone. Will a new drug X decrease depression? We want a clean result. We want to see clear differences in depression between the drug-treated and placebo-treated groups. We want as little variation as possible within the groups. Face it. Too much variation within the treated group, and the drug is not going to market.

Vive la diffe’rence!

Image      Paul solved the problem of individual differences by embracing them. He started his career in the field, trying to figure out why some equatorial animals are seasonal breeders and some aren’t.  Fruit bats (a.k.a., flying foxes) that inhabit particular islands in the Philippines breed only in certain seasons, whereas  those on other islands begin their breeding season months later. Presumably, this ensures that offspring are born at the time when they are most likely to survive. But what is the source of the difference?

      To be a seasonal breeder, you need an internal clock, a reliable cue in the environment to set your clock (like the availability of food or the day length), and a sensory system to detect the environmental cue. Also, you need your clock and your senses to be connected to your reproductive system, and ultimately, to your gonads (ovaries or testes). What’s up with a nonseasonal breeder? Is the clock broken or are they deaf to the alarm? Is there a disconnect between the clock and the gonad?

Now What?

Image     Paul was stuck. He just couldn’t figure this out in the field. In order to uncover the internal brain mechanisms, he needed to have animals in the lab. Commercially available lab animals, however, will not do. They gots no variance in the thing he wanted to study. Most lab animals are uniformly year-round breeders. He would have to create a lab population that had the same variation that exists in nature.

     Being a rebel, he did what all of his colleagues were not doing. He trapped wild mice (Peromyscus leucopus) from the wild, brought them to his laboratory, and began crossbreeding. He kept the population large enough to avoid inbreeding (breeding close relatives tends to decrease heritable variation). Now he had a lab population that contained most of the variation that existed in the wild. How would he make use of this to answer his questions about individual differences in seasonality?

     The next thing he did was brilliant. This base population served as the starting point for a selective breeding program. He started breeding lines of mice that differed in their seasonality. By breeding seasonal males to seasonal females, and unseasonal males to unseasonal females for many generations, he ended up with two groups of animals that differed from each other. They didn’t just differ by accidental inbreeding, or for other unknown reasons. They differed because they were selectively bred for those traits he wanted to study.

     Paul has created and maintained a scientific gold mine. He can expose the two groups to winter conditions, measure their hormones and neuropeptide levels, and figure out what accounts for their differential response to the changing season. He can even sequence their genome and look for differences. He can get answers to questions like “How does evolution change the reproductive system?” “Can natural selection change hormone levels or does it change hormone receptors?” “In nonseasonal animals, is their internal clock broken or are they simply blind to the seasons?”

      To find out the answers, you can check out Paul’s work here and here. Paul writes, “I have worked on multiple populations, but my current mice all come from one population. That’s important to me because I can say that all this variation is just from one little population — and that suggests that other mammals, including humans, might also contain large amounts of variation.”

    I agree and I think it’s especially cool that selection has created wildly different strategies for survival and reproduction within the same species. In this case, you’ve got cautious mice that take the hint that winter is on the way by shutting down the reproductive system in order to conserve energy for survival in the cold. In the same population, you’ve also got flexible mice that will breed willy nilly as long as they can. If the winter is mild, the sexy mice beat the conservatives by producing litters and getting more genes into the next generation. If winter is harsh, the conservatives will win the gamble because they will be the only ones to survive to breed in spring. It takes all kinds. Vive la diffe’rence!

Paul gives a great talk. He gives all of his attention to the students, and he has tons of helpful advice about teaching behavioral endocrinology and science writing. Plus. . .

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