Leah Houri-Zeevi could speak forever about mosquitoes. Many of us, when we think about them at all, think resentfully about the lingering itch that accompanies every mosquito bite. But Houri-Zeevi views this bothersome insect differently. She finds scientific inspiration in the fascinating behavior of mosquitoes, which could help us understand fundamental neural processes across many species — including our own.
Indeed, Houri-Zeevi’s work aims to show that the mechanisms guiding mosquito behavior can be used for studying the molecular basis of memory: the mechanisms that encode memories in the cells of the nervous system. Currently in her first year as a Simons Society Junior Fellow, Houri-Zeevi is working to understand this still mysterious process.
Houri-Zeevi earned a doctorate in neurobiology at Tel Aviv University and is now a postdoctoral fellow in Leslie Vosshall’s lab at Rockefeller University. We spoke recently about the fascinating world of mosquitoes, and what it might teach us about the genetic roots of memory.
Our conversation has been edited for clarity.
What is the molecular basis of memory, and why is it so challenging to study?
When we talk about the molecular basis of memory, what we really mean is: What are the molecules and mechanisms that together generate our ability to recall past events and change our behavior based on experience? We still don’t have a full understanding of how this happens, but it is critical to our understanding of how we learn and retain memories — whether it be remembering where you put your glasses to recalling a birthday party that happened 20 years ago.
There are plenty of theories and experimental findings that can help explain some of what happens as we remember things, but thus far a coherent and complete picture has remained elusive. In fact, we don’t even know whether memory functions the same from species to species, or even within a single species! What we do know is that not all memories are processed the same way. For example, the way we process motor memories — like how we learned to write by hand — is different than the way we process more complex or abstract memories, like recalling the details of a Zoom meeting that happened a few weeks ago.
How do you study this concept in your own work on mosquitoes?
Mosquitoes are obviously a lot different from us, but I am most interested in the basic mechanisms by which the brain and nervous system keep track of past events, and how behavior changes in response to those events. Mosquitoes make for a perfect subject of study to answer these questions. They exhibit a suite of unique and interesting behaviors. And as we learn more about their genetics, we can investigate potential connections between their genes and behavior. These insights might extend beyond mosquitoes and apply to other species — perhaps even ourselves.
Most people find mosquitoes at best irritating. What about their behavior is interesting?
I get this comment a lot! Of course, most of our experiences with mosquitoes are quite awful. I think that everyone has one vivid memory of wishing for mosquitoes to go extinct, or at least that the one mosquito buzzing around the room will disappear and stop turning your night into a nightmare.
However, this is also where mosquitoes become so fascinating to me. For example, studies have shown that female mosquitoes have a special ability to detect and navigate through many different cues when searching for a blood meal. For the female mosquito, this blood meal is not a simple source of nutrition, but instead is needed for the development of her eggs; it plays an essential role in female reproduction.
Indeed, if you’ve ever had a mosquito bite, that was courtesy of a female looking for blood to help develop her eggs. These uniquely female host-seeking and blood-feeding behaviors are tightly linked to the ability of the female to produce progeny and ‘survive’ across evolution. There’s tremendous variation in these behaviors; for example, the females of some species prefer the blood of frogs, and in other species the blood of humans. Behavioral differences such as these are mostly driven by genetic evolution — and therefore hold the key to my research.
Another, related behavior pattern of great interest to me is that female mosquitoes generally only mate once in their lives. Somehow, through a mechanism that we don’t yet understand, this single mating event completely changes the way the female interacts with males for the rest of her life. We also have indications that this single event also changes the way females hunt for blood. I am taking advantage of this rapid and permanent shift in behavior as an entry point into the molecular mechanisms that direct and maintain behavioral changes that last for a lifetime.
How do you plan to decipher the molecular mechanisms that underlie behavioral changes?
Since the behavioral changes I mentioned are so robust and irreversible, we hypothesize that they are directed and maintained through changes in the expression of genes that are expressed and that function in the female before and after mating. The first step is to examine these alterations in gene expression in the brain of the female mosquito after mating and try to understand which differences could explain the effects on behavior. The second step is much more complicated: We must discover how these changes in gene expression are maintained for a lifetime. We think that some of these memories might be preserved in an epigenetic manner, meaning that the mosquitoes keep a memory of this past event via changes in the way that their DNA is ‘read’ in the cells.
That’s our working theory in a nutshell: Epigenetic modifications after mating change behavior so profoundly that the behavioral change is permanent and can’t be reversed, which is why the female only mates once. But this is a work in progress; science at its heart is about testing theories until they can be confirmed or need to be modified. The Simons fellowship allows me to get into the core of these questions and theory.
In addition to being bothersome, mosquitoes can also be deadly. They serve as vectors for harmful diseases, such as yellow fever, Zika and dengue. Does the fact that females only mate once relate to mosquito-borne diseases too?
Absolutely it does. One main strategy for reducing mosquito-borne diseases is to sterilize numerous males so that they cannot produce progeny. If those sterile males mate with a female before a non-sterilized male does so, the female — who only mates once — will not produce any offspring of her own. Over time, the mosquito population should dwindle. This is a good example of manipulating a known behavior pattern to change real-world outcomes. This isn’t my personal focus, but obviously it’s important — and illustrates how a detailed knowledge of behavioral patterns and biology can have a positive impact on society.
What do you hope your work can accomplish?
People have been studying the behavior of mosquitoes for a long time. But in recent years, with the increased power of complementary genetic and genomic studies, we are able to discover so much more — and apply that knowledge to larger questions about behavior and neurobiology.
These days, we collaborate with the Vertebrate Genome Lab here at Rockefeller University —which made an exception for the mosquito and are excited to study these invertebrate animals too! We ‘read’ for the first time the genomes of several non-blood-feeding mosquitoes and compare them to the genetic coding of regular, blood-thirsty mosquitoes. This way, we can gain insight into how genetics controls and alters mosquitoes’ behavior, and together with that the many different aspects that are affected by this change in behavior, such as reproductive processes and even the mosquito immune system. With my work and that of my colleagues here in the Vosshall lab at Rockefeller and around the world, I hope that we will develop a paradigm for how genetic and genomic mechanisms impact behavior — both over the course of a single lifetime and across evolutionary time. This is what interests me most, both during the Simons Fellowship and beyond.