Here’s an itchy fact: Hungry female mosquitoes are often called “flying syringes.” This tiny tormentor has an exceptional sense of smell; after they sniff out a blood meal, they can triple their weight from 2 to 6 milligrams—the equivalent of a few grains of sand.
So, what makes this minute pest so incredibly lethal?
According to the World Health Organization, mosquitoes cause about 600,000 fatalities annually. In highly affected regions, most deaths occur in children under the age of five who get bitten by the Anopheles mosquito that carries the malaria parasite. Globally, the public health impact of all mosquito-borne diseases such as malaria, dengue fever and Zika is expanding due to rising temperatures driven by climate change, more crowded urban centers and the mosquito's remarkable ability to evolve resistance to insecticides.
On World Malaria Day, April 25, we sat down with Ali Afify, PhD, an assistant professor of biology at Drexel, to find out how Dr. Afify and his biology doctoral students are discovering more effective ways to fight the malaria mosquito.
Photo above: The Afify Lab uses calcium imaging assays, like the one shown above, to study the neuronal response of mosquitos when exposed to different smells. (Left) The mosquito’s antenna is fixed under the microscope for imaging. (Right) Neurons on the antenna light up as the mosquito reacts to an odor.
Photos: Ali Afify (top) and Liz Waldie
Why do you love to hate mosquitoes?
Although a mosquito is a tiny insect, it can transmit deadly diseases and is considered the most dangerous animal on earth. I enjoy studying mosquitoes; they are fascinating insects and persistently tuned to find us.
What motivates you to study them?
I want to contribute significantly to the battle against the diseases they transmit. The malaria mosquito, Anopheles, is the most lethal of all—it kills more people than all other mosquitoes combined. Discovering new methods to control this mosquito can save hundreds of thousands of lives, especially in the most economically disadvantaged areas worldwide. This serves my and Drexel University's mission of addressing society's most pressing challenges.
A cluster of mosquitoes feeding on sheep's blood. This blood feeding method is called membrane feeding, because a membrane (parafilm) is used to mimic real skin that mosquitoes bite through to reach a blood meal.
Why are mosquitoes so good at finding people to bite?
Unlike humans, mosquitoes do not have noses. Yet, they are experts at analyzing odors to identify the perfect host for a blood meal. They use olfaction, special receptors on their feet, legs, antennae and proboscis (mouthparts), to quickly process important smells that tell them what and when to bite and where to lay eggs. Interestingly, even if they can't smell us, they use other cues such as heat, humidity and carbon dioxide. This "redundancy" in sensory cues enhances their ability to bite us and find an ideal location to lay eggs.
What is the focus of your research?
To reduce malaria cases worldwide, my lab explores the smells and olfactory receptors that drive different mosquito behaviors, particularly the egg-laying and host-seeking behaviors of the malaria mosquito Anopheles coluzzii. People who study olfaction and taste are chemical ecologists, mainly because we study the chemicals that affect insects. While I consider myself a biologist, I also draw on my experience as a chemical ecologist and neuroscientist to explore the mosquito's olfactory system and research the neurons it uses to detect us.
Phil Baldassari, a technician who works with the Afify lab, examines a mosquito holding cage he assembled.
What is the Afify lab working on?
Mosquitos use their keen sense of smell (olfaction) to detect chemicals on our skin and in the water and use this to make biting and egg-laying decisions. My lab is interested in developing safe repellents that can interfere with this process and prevent biting and egg-laying where humans live. We also want to identify attractants that lure mosquitos to lay eggs in traps and kill them. My lab members include biology doctoral students Huiruo Zeng, who leads the lab's egg-laying project, and Maithili Sawant, who leads the lab's biting project.
Our lab combines various techniques to give us a complete picture of mosquito behavior and the chemicals that attract and repel them. We use behavioral assays to examine the mosquito's actions and test whether a particular chemical can attract mosquito landings or egg laying. For example, we will count the eggs that a mosquito lays on water versus a specific chemical. The chemical is a repellent if it lays more eggs on the water.
In addition, we use calcium imaging to tell us which of the mosquito's neurons respond to different smells. To do this, I developed a novel assay to measure neuronal activity in transgenic mosquitos that are genetically modified so that a specific molecule in the neurons on the antenna lights up when it is activated by a chemical signal. This method adds GCaMP6f, a molecule sensitive to calcium and fluorescence, to all the olfactory neurons in the Anopheles coluzzii mosquito antennae and brain. If an odorant activates the neurons, they produce high fluorescence and light up. This allows us to identify which neurons get activated by a specific odorant.
What excites you most about your findings?
Although our research is hypothesis-driven, the unexpected results are usually the most exciting. For example, my graduate student Huiruo Zeng recently found that an egg-laying repellent for some mosquito species attracts the egg-laying of the malaria mosquito. Interestingly, this chemical kills the eggs of the malaria mosquito. These results were not expected, but they could have a very pragmatic use.
Biology doctoral student Huiruo Zeng, who leads the Afify lab's egg-laying project, records neuronal activity on a malaria mosquito's antennae.
Can you describe the Afify lab’s collaboration with the Creighton lab?
Both labs bring something valuable to the table. Led by Megan Creighton, PhD, an assistant professor of chemical and biological engineering in Drexel’s College of Engineering, the Creighton lab develops nanomaterials that maximize performance and minimize environmental impact. They formulate materials to prevent mosquito-borne diseases; the Afify lab tests them against malaria mosquitos and provides vital feedback to better inform the Creighton lab's processes.
Together, we are working on an innovative repellent that, when applied to the skin, may prevent mosquito bites by decreasing human odorant diffusion. Our skin has many odorants that evaporate and attract mosquitos—we hope this material will greatly slow this evaporation. My graduate student, Maithili Sawant, leads this project and has shown promising preliminary results.
Biology doctoral student Maithili Sawant, who leads the Afify lab's biting project, conducts an experiment on the malaria mosquito's egg-laying response to a specific chemical.
How will your work make a difference?
Our lab's research aims to develop a novel repellent against mosquito biting using chemicals with a high safety profile; these include chemicals commonly used in cosmetics and foods. In addition, we are working to identify long-range olfactory cues—attractants and repellents—of mosquito egg-laying, identify olfactory receptors that respond to these cues and develop new cues that direct egg-laying mosquitoes away from human dwellings and into traps to kill them. By pioneering new mosquito control methods, we can significantly reduce the spread of malaria worldwide.
Members of the Afify lab at Drexel University are working to develop safe repellents that can prevent malaria mosquito biting and egg-laying where humans live.