Exclusive interview: Indian American teen Indeever Madireddy on how he sequenced the angelfish genome

Ritu Jha-

Indian American student Indeever Madireddy who earned global recognition by becoming the first person to sequence the genome of a freshwater angelfish after his pet fish Calvin died in March 2022, spoke to indica about his research going forward.

Madireddy, 17, a student at BASIS in Silicon Valley was born in Mountain View, California. He spoke to indica in detail about his remarkable journey. “I’ve always been interested in biology. I don’t know if I want to be a doctor, but I definitely want to do research in college and hopefully keep doing that in the future.”

He has a large collection of fish at his home aquarium. He got into research in high school to work on science projects and became a member of BioCurious, a community lab in Santa Clara, California that makes advanced equipment available to anyone for a small membership fee.

Madireddy’s research is not restricted to angelfish alone. He has previously completed aquarium fish projects, and that triggered his interest in research.

But the angelfish project “just happened.”

“I had a dead fish and I took my chance,” Madireddy said. “I did it because I wanted to learn more about my fish.”

No one had published the genome sequencing for an
angelfish. “I thought I could do this cool project where I contribute something new to science.”

He said he did not get any credit points in school. “This research has nothing to do with my school,” he said. ”It is more of a passion and a hobby.” Madireddy said he had two angelfish in his home aquarium. “They would always lay eggs but none of them would survive. In August 2020, when they laid more eggs, he was determined to save them. He moved those eggs to a new aquarium, and raised them separately.

“I had around 70 angel fish. They grew from super tiny size to the size of my hand, in the span of a year and a half,” Madireddy said.

In March this year, though, one of the now-adult angelfish died. “It was around this time that I learned that I could do sequencing work and that the angelfish genome has never been sequenced. I was sad when it passed away. I raised it from when it was a tiny egg.”

He said when he sequencing the genome, and analyzing the results, and found that there was another organism’s genome present within my angelfish. It was the genome of a specific bacterium that infects fish. So, it is possible that the fish died from an infection caused by this bacterium. But, unfortunately, I didn’t have enough. I couldn’t say for sure that it was this bacterium that killed the fish. I don’t have enough evidence to say that conclusively.”

He said sequencing a genome is an adventure. “You’re going to have to figure out how to do the sequencing, get the DNA from the fish, all the lab work, all the related computer science work.”

Madireddy said he spent around two months learning all
necessary genomics tools. I put the fish inside a preservative and I froze it at -80 degrees Celsius in the lab. This freezer kept the fish body tissue safe until I could do my research on it.

He explains his work like he would explain a fifth grader. “Every living thing in the world has DNA, the instruction manual for the organism to survive. It has instructions for every biological process, everything that an organism needs to survive. Every organism’s DNA differs a bit. The four nucleotides (Adenine, Cytosine, Guanine and Thymine, called A, C, G and T) make up the DNA of all the organisms in the world, including humans. Every human has a different
combination of these letters. It’s what makes all of us look different, and grow differently.”

Madireddy said he wanted to figure out what do A, C, G, and T mean for the angelfish. “So, I compared my fish genome with tools online to other fish whose genomes have already been sequenced. By comparing fish
to other similar fish, we can figure out based what the other fish has. What does this sequence in the angel fish mean? What does it do? That’s what I did.”

He said the research cost him around $2,000, but he had raised $1,000 with online crowdsourcing.

Madireddy got some attention on social media for his research. “Within a few hours of publishing his research paper, there were thousands of researchers liking and
tweeting, and commenting. It was definitely an interesting experience,” he said. “I am glad that it led to more conversations about my fish, and I hope that other students see the work and are inspired by it and want to do their own research in the future.”

The 17-year-old said he has performed more research and found that the bacterium found in his angelfish can be found in other fish as well. “What’s interesting about this bacterium is that it harms only those fish that are already sick and are not doing too well. Just because this one fish got sick and passed away doesn’t necessarily mean the other fish are doing badly. If there’s something else weakening the immune system, this bacterium will take
advantage of the opportunity and reproduce and take over the fish and make it sicker.”

Madireddy said his next project is RNA sequencing the angelfish so that he can better understand what genes are present in it. “All I have been able to do is compare the fish to other organisms. But maybe there are some genes that are specific only to the angelfish?”

By expanding his RNA sequencing, he said hopes to find new, unique, and interesting things that aren’t there in any other fish.

He said he wants to explore more biology fields in college because “I’ve done all that I can in my lab.”

Not surprisingly, Madireddy was given the 2022 Davidson fellowship and got a $10,000 scholarship for his work on “Stably Integrating CRISPR-Cas9 to Augment the Mammalian Immune System to Protect Against Viral Infections.”

Does he have a guide or a mentor? “Actually, in the lab, it’s about being completely independent. There is no mentorship because I am not yet 18. There are of course other lab members supervising me and making sure I’m safe.”

Madireddy said, “What’s interesting is that with the pandemic going on, I thought that maybe we could take this defense mechanism that bacteria have and repurpose it to function in a human cell and protect a human cell from infections. I did this research at the same lab, and I genetically modified cancer cells to express this CRISPR, the same thing that bacteria have. And I introduced viral DNA, introduced the virus into the cancer cells. It worked!”

He said that it showed that, with CRISPR, these cancer cells were “basically more immune to the virus and didn’t express the virus genes.”

He added, “It stops the spread of cancer cells. CRISPR destroys the cancerous virus’ DNA and prevents the virus from spreading. I wanted to make CRISPR work in human cells. and human cancer cells, and essentially protect the cells from viruses as well, just like they protect the bacteria from viruses. I want to show that CRISPR could protect human cells from viruses. It’s in process, I have already done the research, published a paper and I won the Davidson Fellows scholarship.”