Research models metabolic responses to conserve endangered species

Research models metabolic responses to conserve endangered species

Thomas Raffel, Ph.D. teaches courses in parasitology and ecology. His research explores climate effects on diseases, with specific emphasis on amphibian diseases.

Different species have different responses to temperature, making it difficult to predict how climate will influence the distribution and impact of deadly diseases. Could one metabolic model predict dozens of species’ responses to temperature and acclimation in the fight to save them? 


Infection by the fungus Batrachochytrium dendrobatidis (Bd) causes the disease chytridiomycosis, which threatens hundreds of amphibian species on six of seven continents. 


“The pathogen attacks keratin on tadpoles’ mouth parts, which keeps them from eating properly,” says Thomas Raffel, Ph.D. “Keratin is also throughout the skin of adult frogs, which is important to their physiology because they breathe, get water, and maintain their ion balance through the skin. Bd infects the skin, disrupting these processes enough to kill frogs.” 


Dr. Raffel’s research focuses on how fluctuations in temperature (as opposed to mean temperature) influence parasitic infection. He recently discovered that frogs and salamanders can acclimate their immune systems following a shift to a new temperature, making them more able to fight off infections at this temperature. However, “both host and parasite need time to acclimate after encountering an unpredictable temperature shift.” These delays can make frogs more susceptible to infectious diseases when temperatures fluctuate. 



“We already knew that Bd infection was temperature-dependent, and not in a way that you can predict based on what it is doing in culture. There also has to be temperature-dependence with the host’s immune response,” says Dr. Raffel, assistant professor of Biology at Oakland University. 


Dr. Raffel is creating mathematical models to describe the temperature dependence of Bd infection in the amphibian species he has studied. However, he believes they are still a long way from obtaining generalities, because the temperature- dependence of infection seems to vary among species and it would be impossible to run infection experiments for all the hundreds of species threatened by Bd. 


One possible solution to this problem comes from metabolic theory, which predicts that the temperature-dependence of physiological processes (like the immune system) should reflect the temperature-dependence of whole-body metabolism. “The idea is to estimate key model parameters by measuring metabolic responses to temperature with dozens of species,” he says. “That is where I want to go. I am applying for NSF funds to collect data on temperature dependence of metabolism and Bd infection in multiple species of frogs. 


“The core hypothesis that I want to test is based on metabolic theory,” he says. “The metabolic theory of ecology essentially states that ecological processes and responses to things like temperature are going to be driven largely by, and are going to depend a lot on, the metabolic rates of the organisms in the ecosystem.” 


He got the idea while reading an article by Peter Molnár, whom he would later meet at the 90th Annual Meeting of the American Society of Parasitologists. “They wanted to describe how temperature influences the environmental stage of a nematode parasite and found that development and mortality rates could be predicted using metabolic models, which are based on the equations used to describe enzyme kinetics. So I adapted some of his ideas describing the interaction between host and parasites. 


“In this case,” he continues, “the host has its own equation and the parasite has its own equation. The parasite’s equation describes how well it can infect the host at different temperatures. The host equation describes how well it can resist the parasite. 


“The idea is we cannot measure parasite infectivity or host resistance by itself. They are only meaningful in terms of how many parasites actually were successful. However, we can measure other things about their metabolisms. For example, we can measure a parasite’s swimming speed as a proxy for their ability to infect hosts. For the hosts, we have been measuring oxygen consumption as a metabolic proxy.” 


Dr. Raffel uses these measurements to estimate some of the model parameters describing how temperature should influence parasite infectivity and host resistance. “We then take the actual parasite infection data and use statistics to fit it to a fairly complicated model that mathematically includes both host and the parasite responses. Normally it would be difficult to fit a model like this to raw data, but by estimating some of the parameters from our metabolic proxies, we can really simplify the model-fitting process.” 


This is the first time someone has tried describing a host-parasite interaction using metabolic theory, but Dr. Raffel is excited about the potential for the new approach. “I’ve been amazed by how well these models have worked so far. In several cases we’ve been able to estimate model parameters separately using both respirometry and infection experiments, and the parameter estimates have been remarkably similar.” 


Beyond frogs, there are common patterns to how metabolism works across all species of animal, plants, and microbe and fungus. “We all respond to temperature and body mass in similar ways — these are called metabolic scaling laws.” Metabolic scaling laws are useful because once established, one can predict how almost any organism is going to change its metabolism based on its size and the temperature. 


“You do not have to measure the metabolic responses of all species to get to that kind of generality,” he says. “If you look at enough species and you find that there is a strong correlation with species’ geographic ranges or life history traits, and you can predict how other species are likely to respond.” 


From the perspective of amphibian disease ecology, conservation is the most immediate benefit of Dr. Raffel’s research. “There are hundreds of species of conservation concern that are declining or almost extinct due to infectious diseases. The ones that we are most concerned about are endangered. You cannot do these experiments with them.”