Meet the NLM Investigators: L. Aravind Iyer, PhD, Uncovers the Language of Our DNA

NLM is home to a robust research enterprise. Before the COVID-19 pandemic, I introduced you to two researchers from our Intramural Research Program (IRP), Dr. Lauren Porter and Dr. Xiaofang Jiang.

Now I would like you to meet another one of our researchers, L. Aravind Iyer, PhD. A member of the NLM IRP, Dr. Iyer is a Senior Investigator in the Computational Biology Branch of the National Center for Biotechnology Information. His research revolves around uncovering the stories and patterns held within DNA and RNA and is aimed at unraveling the evolutionary forces that shape biochemical functioning and biological form.

Just like any other biological structure, DNA and RNA evolve over time, which can tell a complex story of an organism’s past and illustrate relationships between organisms that aren’t obvious.

See the infographic below to learn more about the exciting research happening in Dr. Iyer’s lab.

Infographic titled: Language of Our DNA and RNA. Listing the featured researcher, L. Aravind Iyer, PhD and his title, Senior Investigator in Computational Biology. 

The first column of the infographic reads: What I'm Working On. The text in the first column lists Dr. Iyer's short term goals to: (1) Decipher evolutionary relationships of organisms (vertical and lateral) and proteins; and (2) Computationally discover biochemical activities of proteins. Next, long term goals are listed as: (1) Create a unified evolutionary theory for biological conflicts; and (2) Understand the contributions of rapid evolution in conflict on other systems.

The second column is titled: How It Works and lists the following text: (1) Reading an evolving story written in DNA/RNA and protein sequences.

(2) Closing gaps in our understanding by applying computational and statistical methods on databases to compare protein sequences and structures.

(3) Determine vertical (ancestral with a picture of an arrow pointing to  descendant) and lateral (one organism with a picture of an arrow pointing to another organism) flow of genetic information.

The third and final column of the infographic is titled: What It Looks Like and has a book in an indecipherable language with a caption that says: Deciphering the language of life written in DNA/RNA and protein sequences.

Now, in his own words, learn more about the man behind the research!

What do you enjoy about working at NLM?
NLM is one of the world’s leading centers (such can be counted on one’s fingers) for deciphering the biochemistry and biology of proteins through computational analysis of sequences and structures. As a national lab, it has an organizational structure and funding framework best suited for the kind of research that I do, which involves an extensive explorative component.

What makes your team unique?
My team embodies a considerable mass of special knowledge regarding protein evolution and function that we accumulated and systematized over a period of several decades. Given that we look at this using various computational methods, my team melds the expertise of people well versed in biology, computer programming, biochemistry, protein structure, and graph-theoretic analysis.

What is your advice for young scientists or people interested in pursuing a career in research?
I think the most interesting discoveries are those that bring together and illuminate disparate areas of inquiry. Hence, spend your early youth acquiring a very diverse knowledge base and technical capacity. Then organize this knowledge into an interconnected network that you can train your intuition on and draw from when confronted with new problems.

When you’re not in the lab, what do you enjoy doing?
Amateur astronomy, reading and writing about history and ancient texts in the original or translations, recreational mathematics, storytelling.

What inspires you?
Lives of past scientists, philosophers, and leaders from around the world. The profound insights found in the works of the ancients.

You’ve read his words, but now you can hear them for yourself. Follow along on the NLM YouTube page for more exciting content from the NLM staff that makes it all possible. If you’d like to learn more about our IRP program, view job opportunities, and explore research highlights, I invite you to explore the newly redesigned NLM IRP webpage.

YouTube: Dr. Aravind Iyer and the Protein Universe

Video transcript

[Iyer] Early in my life, I wanted to be a paleontologist. And that’s what actually led me to molecular biology. At one level, I could say that I wish to understand the whole protein universe. Proteins can be divided into evolutionary units. There’s a part of a protein that’s preserved over evolution because natural selection is maintaining that part for some reason. And one realization, which dawned on us starting around the early nineties—and this was a very profound realization for all of biology—is that there is a relatively small number of these evolutionary units of proteins, which we term domains, which constitutes the entire protein universe of all organisms across the tree of life.

If we can understand the functions of these units, then that goes a long way towards understanding what organisms do. And given there are many gaps in our understanding of what organisms do, one way to get at it is to first, find all these domains. The second aspect of it is predicting functions for them. The first phase of my research, we captured most of the low-hanging fruit, which were the big families conserved across all organisms.

Now we are moving on to the more difficult terrain, but the difficult terrain also holds a lot of promise because many un-understood functions are hiding within that difficult terrain, and it gives these offshoots in the form of biotechnological reagents. There are things like restriction enzymes, the CRISPR systems, and DNA modification systems. All of these have become very popular reagents.

NLM is a world leader in the analysis of protein sequences, protein structures, and inferring evolution from these bits of information. And this has been a very long-standing interest of mine so, this is the place to be.

Author: Patti Brennan

Director, US National Library of Medicine

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