Meriem El Karoui's love for genomes seems to be written in her genes. She grew up in a family of researchers and shares a remarkable love of numbers with her mathematician mother. This led the young El Karoui to enter the École Polytechnique – known in France as “X” – in Palaiseau in 1990 “with plans to carry out experimental research, in chemistry or physics," and defend a doctoral thesis, an additional programme accredited by the school. During her studies, she discovered "an excellent biology class that was taught in conjunction with high-level experimental work in microbiology". In 1994, she conducted her end-of-study scientific internship at the Microbial Genetics Laboratory in INRA Jouy-en-Josas, where she eventually completed her thesis. “That’s where I discovered the joys of the workbench," declared El Karoui.
Working with mathematicians to understand genomes
Meriem devoted her work to understanding bacterial genome repair. “Just like our DNA, bacterial DNA can be damaged for several reasons. A break in the double helix can lead to a dangerous loss of genetic information. When this happens, the protein that can recognise such damage begins to break down the DNA so that it doesn't stay in the cell. It does some housekeeping! But if there’s a very specific short sequence in the DNA, the protein repairs it. I worked with mathematicians to measure the frequency with which this “repair” sequence appears, since it occurs very often in bacterial chromosomes, and to find out if it appears at random. After leaving X, I was elated to use my research skills." In 1999, El Karoui went to Oxford for a two-year post-doctoral fellowship, where she analysed Bacillus subtilis cell division. Upon her return to INRA, she joined the Dairy Research and Applied Genetics Unit, where she studied resistance to oxidative stress using another model organism, Lactococcus lactis.
Discovering DNA repair signals
In 2003, El Karoui began a personal project on the “architecture of bacterial genomes”. “The number of sequenced bacterial genomes has soared recently, allowing researchers to better understand how they evolve. Some of the bacteria are pathogenic, others are not. We wanted to identify the characteristics of these types of strains. Using the many genomes for a single species – we’re working on a short evolutionary scale - major differences between individuals can already be seen. We’re trying to find out how the bacteria can tolerate this much variability while guarding a portion of DNA intact inside the species. We measured the unchanging and variable portions using a computerised method that compared genomes very efficiently, allowing us to observe what was happening in different regions. For the intact area, rather than working on the essential genes, we wanted to identify the signals needed to “maintain” the DNA. There are quite a number of them. Some are more involved in chromosome organisation, or in the way it positions itself inside the cell during duplication. We were able to use our observations to predict new signals in species where they had not been observed".
A research activist
The young researcher had the freedom to launch this new theme and was supported by her unit. “I'm really glad we have the opportunity at INRA to propose new projects and carry them out.” In 2004, El Karoui was very involved in the États Généraux de la Recherche national consultation. “Right now, French researchers don’t have enough resources to be competitive with our foreign counterparts."
Next September, she will be leaving for a long mission with the Department of Systems Biology at Harvard University in Boston, for a new project on genome evolution. “I'll be working from a different angle in a team of physicists and mathematicians. Nowadays it's possible to see what happens in each bacterial cell in detail, and not just in bacterial populations that are so heterogeneous that only averages can be measured. I'll make the most out of working in a laboratory that has already used these techniques.” She'll be moving there with her partner and three young children in tow. A busy, happy life is in store!
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