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   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    How mosquito brains encode human odor so they can seek us out    
      
     Date:   
         May 4, 2022   
     Source:   
         Princeton University   
     Summary:   
         Some strains of Aedes aegypti -- the mosquito that carries Zika,   
         malaria and dengue fever -- have evolved to bite humans almost   
         exclusively. A team has now discovered how they target us so   
         precisely.   
      
      
      
   FULL STORY   
   ==========================================================================   
   Mosquitoes. Bane of backyard picnics -- and deadly in Zika- and   
   dengue-prone regions.   
      
      
   ==========================================================================   
   Most of the world's mosquitos are opportunistic, willing to drink blood   
   from any nearby source. But in some regions, the mosquitoes that carry   
   Zika, dengue and yellow fever -- Aedes aegypti -- have evolved to bite   
   humans almost exclusively. But to succeed as a specialized feeder,   
   depending on just one species -- ours -- to survive, they must have   
   evolved incredibly precise targeting strategies. How do they do it?   
   "We set out to try to understand how these mosquitoes distinguish human   
   and animal odor," said Carolyn "Lindy" McBride, an assistant professor of   
   ecology and evolutionary biology and neuroscience, "both in terms of what   
   it is about human odor that they cue in on and what part of their brain   
   allows them to cue in on those signals."  After years of dedicated work,   
   including countless scientific and technological challenges, her team   
   has discovered answers to both parts of this equation.   
      
   What is it that the mosquitos are detecting, and how do they detect   
   it? Their results appear in the current issue of Nature.   
      
   McBride described their mosquito-centric approach: "We sort of dove into   
   the brain of the mosquito and asked, 'What can you smell? What lights   
   up your brain? What's activating your neurons? And how is your brain   
   activated differently when you smell human odor versus animal odor?'"   
   Then-graduate student Zhilei Zhao, a 2021 Ph.D. alumnus who is now at   
   Cornell, pioneered their novel approach: imaging mosquito brains at   
   very high resolution to watch how the mosquito identifies its next   
   victim. To do that, he had to first genetically engineer mosquitos   
   whose brains lit up when active, and then the team had to deliver human-   
   and animal-flavored air in ways that the mosquitos could detect while   
   inside the team's custom-built imaging equipment.   
      
      
      
   ==========================================================================   
   Human odor is composed of dozens of different compounds, and those same   
   compounds, in slightly different ratios, are present in most mammal   
   odors. None of those compounds is attractive to mosquitoes by itself,   
   so the challenge was to determine the exact blend of components that   
   mosquitos use to recognize human odor.   
      
   The team concluded that two chemicals, decanal and undecanal, are   
   enriched in human odor. They patented a blend featuring decanal that   
   they hope could lead to baits attracting mosquitoes to lethal traps,   
   or repellents that interrupt the signal.   
      
   To provide comparison mammals to test, graduate student Jessica Zung   
   worked with former research specialists Alexis Kriete and Azwad Iqbal   
   to collect hair, fur and wool samples. For this paper, the team used   
   odor from sixteen humans, two rats, two guinea pigs, two quail, one   
   sheep and four dogs. Howell Living History Farm in Hopewell, N.J.,   
   donated several fleeces from their spring sheep shearing; for another   
   domesticated mammal, Zung went to a grooming salon and gathered trimmed   
   hairs from recently groomed pet dogs.   
      
   "For the human samples, we had a bunch of great volunteers," Zung   
   said. "We had them not shower for a few days, then strip down naked   
   and lie down in a Teflon bag." Why naked? Because cotton, polyester and   
   other clothing fibers have their own smells that would distort the data.   
      
   Once they conquered the technical challenges -- retrieving the human   
   and animal odors nondestructively, designing a system that allowed them   
   to puff human odor at the mosquitos in the imaging setup, creating a   
   wind tunnel to test simple blends or single compounds, and breeding   
   viable strains of mosquitos whose brains respond to the equipment --   
   they began gathering data.   
      
      
      
   ==========================================================================   
   Very surprising data.   
      
   Before this study, researchers speculated that mosquito brains must have   
   a complicated, sophisticated technique for distinguishing humans from   
   other animals. Quite the opposite, it turned out.   
      
   "The simplicity surprised us," said McBride. "Despite the complexity   
   of human odor, and the fact that it doesn't really have any kind of   
   human-specific compounds in it, the mosquitoes have evolved a surprisingly   
   simple mechanism for recognizing us. To me, it's an evolutionary story:   
   if we created a statistical test to differentiate human odor, it would   
   be very complex, but the mosquito does something remarkably simple, and   
   simple usually works pretty well, when it comes to evolution."  In other   
   words, simple solutions tend to breed true, over evolutionary time.   
      
   Mosquito brains have 60 nerve centers called glomeruli (singular:   
   glomerulus).   
      
   The team had hypothesized that many -- maybe even most -- would be   
   involved in helping these human-dependent mosquitos find their favorite   
   food.   
      
   "When I first saw the brain activity, I couldn't believe it -- just two   
   glomeruli were involved," Zhao said. "That contradicted everything we   
   expected, so I repeated the experiment several times, with more humans,   
   more animals. I just couldn't believe it. It's so simple."  Of the   
   two nerve centers, one responds to many smells including human odor,   
   essentially saying, "Hey, look, there's something interesting nearby you   
   should check out," while the other responds only to humans. Having two   
   may help the mosquitos home in on their targets, the researchers suggest.   
      
   That was one of the biggest "Eureka!" moments in the project, said   
   McBride.   
      
   "Zhilei had worked for a couple years to get the transgenic mosquitoes   
   that he needed, and then we found that we didn't have a good way to   
   deliver human odor.   
      
   So we worked for another year or two, coming up with ideas to try to   
   figure out how to deliver enough human odor in a controlled enough way   
   to see a response.   
      
   Then, the first time we tried this new technology that we described   
   in the paper -- this new way of delivering odors -- he actually saw a   
   brain respond.   
      
   It was incredible."  By determining the glomeruli that mosquitos use to   
   detect humans, and identifying what it is they are detecting -- decanal   
   and undecanal -- the team has an elegantly straightforward answer to   
   their questions, noted Zung.   
      
   "If this were purely a neuro imaging paper, there would be some questions   
   remaining," she said. "If this were purely an odor analysis paper,   
   there would still be unanswered questions. A purely behavior paper,   
   same thing. But one real strength of this project is that we were able   
   to bring in so many different methods and the expertise of so many   
   people. And Lindy was just amazing and willing to learn about and invest   
   in all these different methods."  "This entire project is incredibly   
   collaborative," Zhao agreed. "We were tackling so many lines of evidence   
   that have now converged into a cohesive story, and that requires so much   
   different expertise. I hadn't studied any neuroscience before I came   
   to Princeton, but we have the Princeton Neuroscience Institute here,   
   with so many talented people I could learn from. For the odor science   
   part, I have no background in that, but Jessica is an expert. And for the   
   wind tunnel setup, we collaborated with researchers in Sweden. If we had   
   done everything ourselves, we might not have gotten such good results;   
   it's only through collaboration that we got here."   
      
   ==========================================================================   
   Story Source: Materials provided by Princeton_University. Original written   
   by Liz Fuller- Wright. Note: Content may be edited for style and length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. Zhilei Zhao, Jessica L. Zung, Annika Hinze, Alexis L. Kriete, Azwad   
         Iqbal, Meg A. Younger, Benjamin J. Matthews, Dorit Merhof,   
         Stephan Thiberge, Rickard Ignell, Martin Strauch, Carolyn   
         S. McBride. Mosquito brains encode unique features of human odour   
         to drive host seeking.   
      
         Nature, 2022; DOI: 10.1038/s41586-022-04675-4   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2022/05/220504130829.htm   
      
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