At first glance, Caenorhabditis elegans, or C. elegans for short, isn’t exactly awe-inspiring. This transparent roundworm, about 1 millimeter long, is essentially a set of liquid-filled tubes surrounded by a flexible exoskeleton; its huge gut starts at one end with a mouth, also known as the pharynx, and ends in the anus.
As unremarkable as the worm may seem, in the past few decades it has contributed a great deal to medical science: seminal discoveries about programmed cell death, a process that is key for normal development but also plays an important role in cancer, were made using C. elegans and earned the Nobel Prize in Physiology or Medicine in 2002. Iskra Katic, the head of the FMI C. elegans facility, tells us about her job and how this tiny worm can help researchers understand the building blocks of life.
From your PhD to your current job, you’ve always worked with C. elegans. What do you like about this model organism?
My PhD program in the US had three rotations, and I initially thought I would want to join the mouse lab, but I liked the worm lab more — I just really liked the simplicity and the clarity of the system.
Why is C. elegans a good model system for scientific research?
About 70% of worm genes are conserved to humans and the pattern of divisions from the fertilized egg to the adult, as well as the fates of individual cells, are completely elucidated. The worms are transparent, so you can see every cell, and they are easy to cultivate and cheap to maintain. Their life cycle is about three and a half days at 20°C, and it’s mostly a hermaphroditic species: a worm usually self-fertilizes its eggs and one adult gives about 300 progeny, so they’re super useful for genetics because you have enough numbers to analyze. C. elegans is also a popular model organism in neuroscience because it has only 302 neurons and all of the connections between these neurons have been elucidated.
Why was C. elegans chosen as a model organism in the first place?
Some 50 years ago, South African biologist Sydney Brenner was looking for a genetically tractable organism with a small and easily measurable neural system. That was all true for C. elegans, so Brenner came up with the founding techniques of C. elegans maintenance, crossing, genetic nomenclature and genetic screens.
How can studying C. elegans teach us about humans?
A lot of fundamental biological processes were first discovered in worms. C. elegans has taught us a lot about genes involved in ageing: it is very easy to do ageing experiments in a short-lived organism because you can see when a mutation in a gene prolongs or shortens the animal’s lifespan. Scientists have also elucidated a lot of basic signaling pathways using C. elegans, and RNA interference as a technique was first done in plants and in C. elegans. [For RNA interference, a form of gene silencing by double-stranded RNA, Craig Mello and Andrew Fire were awarded the Nobel Prize in Physiology or Medicine in 2006.]
Tell us something about your job as head of the C. elegans facility at the FMI.
My team includes research associate Lan Xu and myself. Part of my job is discussing with researchers what kind of approaches might be useful for somebody’s project on C. elegans — for example, I give advice on genetic screens, on crosses, which kind of strain should be made, what should be ordered. Then I do transgenesis, which involves microinjecting DNA, RNA or proteins into the worm’s gonad for the generation of transgenic animals, including CRISPR-edited animals. In fact, we were one of the first groups to show that the gene-editing tool CRISPR works in C. elegans in 2013. In the last three to four years, I’ve also started doing some work with the freshwater invertebrate Hydra, trying to translate the genetic tools that we have in worms to Hydra. I’ve been doing some CRISPR in Hydra, as well as RNA interference. Another thing that I do is using worms to test specific processes or proteins for FMI researchers who study them in a different model system.
What do you like the most about your job?
When you’re a scientist, there are things that work and things that don’t work; when you’re involved in multiple projects, like me, there will always be something that’s working. You can also help where things are not working for someone else. I really like being helpful to people. Also, researchers are very different in how they do their science: different people have different strengths and different approaches — that’s fun.
What’s one thing that people couldn’t find out about you by looking at your CV?
At one point during my PhD, I directed a small choir. It was totally amateurish, we had people saying what kinds of songs or melodies they would like to sing — sometimes it was classical choral music, other times it was songs from musicals.
’ More about the C. elegans facility at FMI
About Iskra Katic Iskra Katic was born in Zagreb, Croatia. She studied biology at Carleton College in Minnesota and then completed a PhD at Columbia University in New York. She then moved to France to do a postdoc at the Úcole Normale SupÚrieure in Paris. She joined the FMI as head of the C. elegans facility in January 2010. Iskra lives in Basel and enjoys gardening and reading.