Fruit flies shed light on how immune responses are regulated

Featured Scientist: Pooja Kadaba Ranganath (she/her/hers), PhD (Anticipated: January 2022), School of Biological Sciences, Illinois State University

Two pictures of Pooja KR. In one, she stands in front of the river holding a cup of coffee. In the other, she stands in a museum next to an image of a human body.
Pooja enjoying hot chocolate from Ghirardelli near the Chicago River (left) and exploring a science museum in Washington D.C (right).

Birthplace:  Bangalore, India

My Research: In my research, I work to understand how the immune system works and how it defends itself against germs that can cause sickness, also called pathogens.

Research Goals: I want to work at the intersection of two types of science, basic and translational. The goal of basic research is to learn how a particular system works. The goal of translational research is to apply the information that we learn from basic research to help humans. My main interest is to do research to understand cancer and help make personalized medicine a reality for patients.

Career Goals: I want to help advance medicine by working in the industry research setting.

Hobbies: In my free time, I like to cook, spend time with friends and family, try out new food, and practice a classical form of Indian music. I also love to travel and explore new places.

Favorite Thing About Science: Cells are amazing to me. It is fascinating to explore the mysteries of the body and use that information to support human health. Science allows you to explore new questions. I love the feeling that my work can make a difference to people who are in need.

My Team: The research for this paper was made possible with the help of Jonathan Lee, an undergraduate student who helped me do the experiments, and the principal investigator, who supervised us throughout the process.

Organism of Study: The fruit fly, also called Drosophila melanogaster.

A picture of a fruit fly. It had red eyes and a light brown body.
Image source: Wikimedia Commons

Field of Study: Cellular Immunology

What is Cellular Immunology? Cellular Immunology is a type of biology. When a person is infected with a pathogen, the immune system is activated to destroy the pathogen before the person can get sick. Researchers in the field of cellular immunology will study the cells and molecules of the immune system to understand how they all work together to protect the body.   

Check Out My Original Paper: “The S1A protease family members CG10764 and CG4793 regulate cellular immunity in Drosophila”

QR code to the original publication

Citation: KR, P, Lee, J, Mortimer, NT. 2021. The S1A protease family members CG10764 and CG4793 regulate cellular immunity in Drosophila. micropublication Biology. (Doi: 10.17912/micropub.biology.000370)

Article written by Rosario Marroquin-Flores, PhD (Anticipated: August 2022), Illinois State University

Research At A Glance: The immune system plays an important role in protecting our bodies against pathogens. When exposed to a pathogen, the body will turn on immune cells to help defend the body against infection. This is called the immune response. To understand how the human immune system functions, scientists often study the immune systems of other animals. In our research, we used the fruit fly and a parasitic wasp to learn more about the immune response. In nature, parasitic wasps can infect flies by laying their eggs inside the body of the fly. When the wasp infects the fly with its eggs, the immune system of the fly will activate to kill the parasite. Special immune cells in the fly recognize the infection, bind to the wasp egg, and surround it with several layers of proteins in a process called encapsulation. During encapsulation, immune cells surround the egg and harden to stop the wasp from getting vital nutrients, killing the parasite. In our research, we identified two important genes called CG10764 and CG4793 that may impact the fly immune response. To figure out what these genes do, we turned them off and measured how the absence of these genes impacted the encapsulation process. We found that these two genes have opposite roles. One gene is involved in turning on the immune response, while the other is involved in turning off the immune response.

Highlights: One important cell involved in the fly immune response is called a lamellocyte. Lamellocytes are immune cells that turn on in response to infection and help form the capsule that kills the wasp parasite. In this study, we turned off our two genes of interest, CG10764 and CG4793, in lamellocyte cells.Then, we watched to see if the fly was still able to encapsulate the wasp egg. Figure 1 is a boxplot that shows how encapsulation changed when our genes of interest were turned off. 

A data figure that shows the percent of encapsulated wasp eggs when CG10764 and CG4793 are turned off. In unchanged cells, around 50% of eggs are encapsulated. When CG10764 is turned off, around 25% of eggs are encapsulated. When CG4793 is turned off, around 80% of eggs are encapsulated.
Figure 1. The percent of encapsulated wasp eggs when CG10764 and CG4793 are turned off in lamellocyte immune cells. The y-axis (vertical) shows the percentage of eggs that were encapsulated. The x-axis (horizontal) shows which gene was absent. Figure adapted from KR et al. 2021.

The letters in Figure 1 show the results of the statistical test. When the letters are different, that means that the percentage of wasp eggs encapsulated by the fly changed. We see that the percentage of eggs encapsulated went down when CG10764 was removed from the cell, compared to unchanged cells. We can see this because the boxplot for “CG10764 gene absent” has a “B” above it while the boxplot for cell unchanged has an “A” above it. We see the opposite effect for CG4793. We see that the percentage of eggs encapsulated went up when CG4793 was removed from the cells because the boxplot for “CG479 gene absent” has a “C” above it while the boxplot for cell unchanged has an “A” above it.

These results suggest that CG10764 may activate the fly immune response to help it fight against the infection. When CG10764 is absent, the fly has a harder time encapsulating the wasp eggs. Our results also suggest that CG4793 can turn off the fly immune response. When CG4793 is absent, the fly is better at encapsulating wasp eggs. We think that these two genes work together to help regulate the immune system when the fly is infected. CG10764 turns on the response and CG4793 turns it off.

What My Science Looks Like: In our research, we work with fly larvae, these are immature flies that have not yet grown their wings. We allow the parasitic wasps to lay their eggs inside the body of the larvae. It usually takes 72 hours for the fly to encapsulate the wasp eggs.  The image below shows a fly larva with an encapsulated wasp egg inside it.

A picture of an infected fly larva under a microscope. The larva looks fat and grub-like. The encapsulated wasp eggs look like hard black ovals.

Microscopic image of a fly larvae infected with a wasp egg. This fly has successfully encapsulated the wasp parasite. Image adapted from Mortimer et al. 2012.

Recall that lamellocyte cells are immune cells that help form the capsule that kills the wasp parasite. The image below shows what a lamellocyte looks like under the microscope. 

A picture of a lamellocyte cell under a microscope. The cell looks amoeba-like and gelatinous.
Microscopic image of a fly lamellocyte cell.

The Big Picture: In this study, we start to get a better understanding about how the fly immune response is regulated. The fruit fly is a model organism, which means that it has been very well studied and there are many tools available to understand the genes of the fly. Model organisms are often used to study human diseases and several parts of the immune response in the fruit fly can be applied to humans. In our research, we have identified two genes that may help regulate the immune response and this might help us to understand human immune systems too.

 Decoding the Language:

Basic research: Basic research is a type of research with the goal of understanding a particular phenomenon or law of nature. The goal of basic research is to advance knowledge in a particular topic.

Boxplot: A boxplot is a graph that shows you information about the spread of your data. The top line of the box shows the 75th percentile. This is where 75% of the data fall below the line, and 25% of the data fall above the line. The line in the middle of the box shows the 50th percentile, or the middle of the data. The bottom line shows the 25th percentile. This is where 25% of the data fall below the line and 75% of the data fall above the line. The lines that extend from the box in either direction are called whiskers. They show the range of the highest values and the lowest values of the data set.

Encapsulation: Encapsulation is the process of enclosing something. In the context of this research, it is the process of surrounding the wasp egg with layers of protein that harden around the parasite to kill it.

Gene: A gene is a unit of heredity passed from parents to offspring. Genes normally code for proteins that have certain functions in the body.

Immune response: An immune response is the reaction that the body has when it encounters a pathogen. The purpose of this response is to defend the body. In the context of this research, the immune response of the fly is to activate the immune cells that the fly needs to encapsulate the wasp egg.

Lamellocyte: A lamellocyte one of several types of immune cell that is turned on when the body identifies an infection, and these cells play a role in the encapsulation process in flies.

Larvae (plural): A larva (singular) is the immature form of an insect. Larvae often look very different from the adult form of the insect. As the larvae grow, they will change to look more like the adult version of the insect.

Model organism: A model organism is a non-human species that is very well studied and is used to learn more about other species. Model species are frequently used to study human disease.

Pathogen: A pathogen is a bacteria, virus, or other microorganism that can cause disease.

Principal investigator: A principal investigator is the person responsible for organizing and managing a research project or lab. In colleges, faculty often serve as principal investigators and run research labs with graduate and undergraduate students.

Translational research: Translational research is a type of applied research with the goal of improving human health.

Learn More:

University of Arkansas Medical Sciences (AKMS) information on translation research

National Institutes of Health (NIH) information on model organisms

Dros4schools information on the fruit fly as a model organism

A video of a wasp laying eggs inside a fly larva

Article edited by Brooke Proffitt, B.S. in Zoology, University of Illinois-Alumni.

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