Willem Laursen, PhD

Postdoctoral Research Fellow
Garrity Lab
Brandeis University
(September 27, 2019)

A molecular driver for mosquito heat-seeking

Mosquitos are attracted to humans – we can all feel the itch just thinking about a bite from these pests. But what drives this behavior? How do mosquitoes seek out a human or animal to bite? Dr. Laursen explains how two ion channels (openings in a cell membrane that let molecules through) are responsible for heat seeking in the fruit fly. His work shows that similar channels are necessary for heat seeking in mosquitos.

Mosquitoes serve as vectors for malaria, dengue, yellow fever, West Nile virus, and others, making them arguably the deadliest animal on the planet. Infected female mosquitoes seeking a bloodmeal spread disease by locating, and subsequently biting, human hosts--something they accomplish through a combination of visual, chemical, and thermal cues. Although the importance of these cues has been appreciated for decades, the molecular sensors remain largely unknown. Using Anopheles gambiae (the major malaria vector for sub-Saharan Africa) as a model system, my work aims to better understand the cellular and molecular bases for the detection of host-relevant stimuli in mosquitoes, with the current focus on heat-seeking.

To identify the molecules responsible for driving this behavior, we turned to our work on the Drosophila thermosensory system for inspiration. Our lab has previously demonstrated that two warm-activated ion channels, dTRPA1 and Gr28b.D, are required for proper responses to warm temperatures. However, work from others has shown that neither is required for mosquito heat-seeking. More recently, we identified a member of the Ionotropic Receptor family (IR21a), invertebrate-specific relatives of glutamate receptors, that activates in response to cooling. Surprisingly, this receptor is required not only for Drosophila behavioral avoidance of innocuous cold but also warm temperatures.

Based on its ability to function as a derivative thermosensor across a range of temperatures and control Drosophila behavioral responses to warmth, we probed the role of IR21a in mosquito host-seeking using molecular genetics, physiology, and behavioral experiments. Similar to Drosophila, we found that IR21a is expressed in antennal thermoreceptors that respond to decreasing temperatures. Mutant mosquitoes show dramatically reduced attraction to a heated peltier element and lose their strong preference for warm blood, indicating IR21a serves as a critical driver of heat-seeking. This suggests that a conserved cooling receptor molecule has been co-opted over the course of evolution to suit specialized--and in some cases apparently opposing--behavioral roles (i.e. avoidance of warmth in Drosophila and attraction in female mosquitoes). Interestingly, hematophagy (blood-feeding) in insects is believed to have independently evolved multiple times, raising the question of whether other lineages have converged on the same molecular mechanisms for host seeking. Such knowledge will be important for rational design of new strategies for vector control.