A Swiss Army Knife for Biology
Jeremy Joseph
“WHAT THE HELL IS WRONG WITH YOU?” my middle school PE teacher yelled when I showed up to class with a live frog I had just caught. That question could have been the soundtrack of my childhood. I was always obsessed with how living things worked: trying to perform mouth-to-mouth resuscitation on a dead lizard with a straw or spending recess catching bugs for my pet spiders. That singular, hands-on curiosity, the drive to take life apart and understand its processes, eventually led me from catching insects in the bushes to studying molecules in the lab. Today, as a PhD student in the Buchan Lab at the University of Arizona, that same drive pushes me to tackle one of biology's greatest mysteries: how cells organize and regulate the thousands of messenger RNAs (mRNAs) that determine when, where, and how proteins are made.
Every cell is a bustling, complex factory that continuously reads, copies, and interprets genetic information. Although DNA contains the blueprint of life, it rarely acts alone. Instead, cells first create temporary copies of genetic information called messenger RNAs, or mRNAs. These mRNAs carry instructions from DNA to the cellular machinery that builds proteins, the molecules responsible for nearly every task our bodies perform. But cells don't simply make mRNAs and leave them alone. They carefully control when each mRNA is produced, where it travels, how long it survives, and whether it is translated into protein immediately or stored for later. When this system breaks down, the consequences can be devastating. Defects in mRNA regulation have been linked to neurodegenerative diseases such as Alzheimer's disease and ALS, as well as many forms of cancer. To develop better treatments, we first need to understand how mRNAs are regulated inside living cells.
Halo and SNAP tags being used simultaneously. Here, SNAP allows us to visualize the nucleus (green) while Halo enables visualization of the cytoplasmic stress granule associated protein, Ded1 (magenta).
In the past, scientists have often studied these molecular events one mRNA or one process at a time. But this is like trying to understand how a complex computer works by only looking at one tiny wire. We need a way to look at the entire system at once, and that requires new tools. My research aims to solve this limitation by building novel, cutting-edge, genome-wide libraries in budding yeast (Saccharomyces cerevisiae). We use yeast because it shares many core molecular pathways with human cells but is genetically simpler and much easier to manipulate.
Playing tag with RNA
The tool itself is essentially a molecular "Swiss Army knife" for cell biology. We tag virtually every messenger RNA in the cell with tiny, versatile molecular labels using the Halo and SNAP systems. These tags allow us to quickly and brightly label mRNAs, track where they go inside the cell, or isolate them for deeper study. Crucially, we are also building complementary libraries to tag virtually every protein in the cell with the same versatile labeling systems. This unified approach allows us to see how the entire system—both the mRNA blueprints and the finished protein products—is behaving.
Example image of mRNA labeling. Here, SNAP allows us to visualize PGK1 mRNA (small foci) as well as the nucleus (larger circle) of each cell.
With this toolkit in hand, I am systematically investigating how mRNAs are organized and regulated across different physiological conditions, including cellular stress and aging. I use high-throughput microscopy to image thousands of different mRNAs across the genome, allowing me to watch how they move, where they localize, and how their behavior changes as cells respond to different environments. By comparing these patterns across many different genes, I hope to uncover the fundamental rules that govern mRNA localization and regulation.
By generating this "Swiss Army knife" and making it openly available to the entire scientific community, we are lowering the barrier for entry for other researchers. This tool will allow labs around the world to accelerate the study of countless aspects of RNA and cell biology, potentially leading to new biotechnological breakthroughs and, most importantly, revealing the fundamental principles of life. Ultimately, I hope to tackle these intricate problems from a systems-level perspective. Guided by the same curiosity that once made me put a straw in a lizard, I aim to build tools that help scientists better understand how cells work and, ultimately, contribute to developing future treatments for diseases caused by failures in gene regulation.
As of Fall 2026, Jeremy Joseph is 3rd year BMCB student.