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Emma Bruder, doctoral student in microbiology

Research paths

The bacteria responsible for inflammation of the digestive tract ! This is the subject of research by Emma Bruder, a doctoral student in microbiology at the Centre interdisciplinaire de recherche en biologie (CIRB) at the Collège de France.

Your research is related to Crohn's disease..

I'm working on what we call AIECs, Adherent and Invasive Escherichia coli, which are bacteria involved in Crohn's disease. This pathology is due to various factors, both genetic and environmental, and causes intestinal inflammation in particular. This work is part of a team studying the adaptation of bacteria to their environment. Firstly, in the relationship between pathogenic bacteria and their host during infection, and secondly, in the organization of their chromosomes. Bacteria have no nucleus like eukaryotic cells (human or animal). They usually have a single circular chromosome that carries most of their genes. We are studying how the chromosome is repaired when altered, how it is organized in the bacterium and how the genes it carries are expressed in response to environmental changes.

How are they involved in disease ?

In this pathological context, bacteria will take advantage of the weakening caused by the disease to invade the digestive tract. Although they are not responsible for the disease, they do play a part. Inflammation of the digestive tract is maintained by these bacteria. This is because they are able to adhere to and cross intestinal cells, as well as survive in the immune cells that would normally eliminate them. Not only are they able to maintain themselves there, they are also able to multiply. The immune cells become their new ecological niche, their new habitat. Our team has shown that these bacteria are able to do this because they unite with each other. It's as if they were recreating a multicellular being, producing around themselves a shield of proteins and sugars that protects them from the aggressions of the immune system.

How is inflammation triggered ?

Inflammation is our body's defense response to injury or pathogen implantation. It's the same, but in our intestines. If the wall is damaged, inflammation sets in. In addition to this degradation, the microbiota (a collection of micro-organisms living in the digestive tract) will be disturbed. It's a question of the balance of these micro-organisms. If all goes well, the good bacteria will line this famous wall and protect us from the bad bacteria. If there's an imbalance, as in the case of Crohn's disease, the pathogenic bacteria will implant themselves in the immune cells, which, unable to kill them, will send out signals to increase their defenses. It is this mechanism that sustains and exacerbates the inflammation present in this pathology.

How do you study these mechanisms ?

I work with clinical strains, i.e. bacteria taken from patients suffering from the disease. I try to determine which mechanisms and genes enable them to resist the immune system. To do this, I observe their genome - around five thousand genes for each strain - and look to see whether groups of genes common to several of these strains could explain this resistance. I trigger infections in immune cells and see if the bacteria manage to survive. How many days ? Which genes will they activate to do so ? Is there a collective adaptation strategy ?

What are the stakes and possible consequences of this research for people with Crohn's disease ?

This research will not cure Crohn's disease. The hope is rather to relieve the chronic inflammatory crises caused in part by these bacteria. They are particularly distressing for patients. We usually use antibiotics to eliminate the bacteria, but that's impossible in this case. It doesn't work, because they're in the macrophages - immune cells commonly known as white blood cells - and they form the shield I was talking about. The challenge of my thesis is to understand which genes enable this protection to be set up, and eventually to find molecules that could prevent the creation of this protein shield.

Do you have a routine for conducting your research ?

I usually arrive between 8 and 8   30, and then it depends on my tasks at the time. My research involves molecular biology, because we need to visualize bacteria precisely. We stain them with fluorescent colors to make them stand out. This is genetic modification, adding or removing genes. It takes a lot of time. Once these strains have been constructed, I use them to infect macrophages. They too need to be prepared in advance : every two days, their medium needs to be changed. Once they are infected, I stop the infection at a precise moment. We call this " fix ". Finally comes the time for analysis, by microscopy or flow cytometry. A laser beam passes through the fluorescent bacteria, enabling us to quantify and qualify them more automatically. I can therefore obtain important information on the number of AIEC bacteria that have infected immune cells over a given period of time. Sometimes, it's even necessary to count them visually !

What triggered a desire for this subject of study to the point of making it the focus of your research ?

It came about quite simply. After my bachelor's degree, I wanted to work in the natural sciences. I hesitated about studying medicine, but ended up choosing the Faculty of Science. In my third year of undergraduate studies, we could specialize in one of three subjects : animal physiology, plant physiology or the physiology of micro-organisms. I opted for the latter, as the techniques and problems were stimulating. I loved bacteria. I found their faculties fascinating, such as their ability to evolve very rapidly according to their living conditions. The research around them seemed very interesting, and working on pathogenic bacteria brought me closer to health issues. My final year at the Institut Pasteur convinced me to continue in this field.

Do you plan to continue your research after you've defended your thesis ?

After my PhD, I'd like to do a postdoctoral fellowship in an English-speaking country. This would enable me to practice the language in immersion, as well as experiment with other ways of working. I'm still motivated to continue with microbiology, but perhaps on different bacteria. For example, I'm very interested in antibiotic resistance. It's a major public health issue. In any case, it's important for me to stay in research that has human health applications.

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Emma Bruder works in the Chromosome Dynamics team at the Centre interdisciplinaire de recherche en biologie du Collège de France, under the supervision of Dr Olivier Espeli.Her thesis is entitled " Characterization of intracellular communities formed by E.coli associated with Crohn's disease ".

Photos © Patrick Imbert
Interview by Aurèle Méthivier