Research

For me, biological research is a series of puzzles that I enjoy trying to solve, concerning the origins and mechanics of life. For anyone who’s interested in a longer, more formal description of my past research, I’ve posted a link to my PhD thesis. I also have a brief summary that expands on the research I’m undertaking with undergraduate researchers in a more formal research statement.

Because most of the instructions required for organisms to function are transmitted in DNA (or occasionally RNA), it’s possible to track the changes life has undergone by sequencing DNA and comparing the sequence across organisms. The portions that differ between species are likely to be unimportant or involved in species-specific processes, while the portions that are constant may indicate essential regions universally required for life. Equally importantly, not all DNA is functional, and the ‘functional’ portions are constantly changing over time. Many of these regions are preserved long after they lose function, creating a record of past events. I’m broadly interested in studying how genomes change over time, and using reconstructions of the events preserved in the DNA “fossil record” to see how evolution works.

My thesis research had two main components. The first component was a study of proteins known as piRNA proteins, that work in concert with RNA molecules known as piRNAs to suppress transposable elements. Transposable elements are fascinating regions of DNA that have gone ‘rogue’. Instead of encoding instructions for the organism, they encode instructions for duplicating themselves. They copy and paste themselves (or cut and paste) across the genome at random. Often this leads to genetic diseases, but occasionally transposable elements make a mistake, and copy regions of the host genome, which can lead to new genes. Some transposable elements originated as viruses, and have a limited ability to move into other cells and even infect other species, occasionally transferring genes in the process. Genomes are filled with dead (and a few living) copies of transposable elements. Roughly half of the human genome, for example, is made up of transposable elements. I like to think of piRNAs as transposable elements that have ‘switched sides’. piRNAs derive from transposable elements that copy into regions of the host genome where they can be processed to form small RNAs. Anything matching the small RNAs is recognized as foreign, and suppressed by host proteins known as piRNA proteins. In some of my thesis work, I studied the rates at which piRNA proteins change, or evolve, over time to combat the changing threats posed by transposable elements in several species of fruitfly.

The second component of my research involved microRNAs. MicroRNAs are small RNAs that work in a superficially very similar manner to piRNAs, only instead of suppressing transposable elements, microRNAs target host genes, suppressing the expression of host genes that shouldn’t be expressed. Nearly all animals have microRNAs, and many of these microRNAs are nearly as ancient as animals themselves. An individual microRNA can suppress hundreds of genes, but not all of the genes that can be suppressed are suppressed, and of those that are suppressed, some are newly evolved genes, and others are ancient genes. There are thus at least two possibilities for ancient microRNAs. One is that ancient microRNAs are shared across many organisms because they target ancient genes with essential roles. The other is that ancient microRNAs are always important, but are constantly changing roles over time. In graduate school, I compared the targets of microRNAs to other sequences, to see which microRNAs change targets at the slowest vs. the fastest rates, while in my postdoctoral research I’ve been comparing the targets of microRNAs to simulated neutrally evolving genes, using some scripts that I’ve written.

I’ve had a great time investigating these questions, but genomes are large, and there are a lot of interesting questions I could never tackle on my own, because there isn’t enough time to give each question the attention it deserves. I’m looking forward to giving undergraduates the tools needed to ask some of these questions with me (and afterward, on their own). These days, all anyone needs to contribute to assembling the puzzle of the history of life on earth is a computer and an internet connection. It’s a great time to be alive.