The aim of Allon Weiner is to understand how the Candida albicans yeast – a microorganism present in 80% of us – can sometimes turn pathogenic and lead to severe systemic infection. Thanks to ATIP-Avenir Program funding, the young researcher uses innovative light and electron microscopy techniques to visualize the initial moments of infection with this yeast.
Pneumocystosis, aspergillosis, candidiasis… each year, fungal infections are responsible for as many deaths as tuberculosis or malaria. One of the pathogens involved is the yeast Candida albicans, which colonizes the skin, oral cavity, genitals and intestinal mucosa of most healthy individuals. Under specific conditions and in susceptible patients, C. albicans can invade the gastrointestinal mucosa and enter the bloodstream, leading to severe systemic infection. "After my second postdoc – at the Valrose Institute of Biology in Nice – on Candida albicans cell biology, I wanted to decipher the little-known mechanisms that enable Candida albicans to pass through the human epithelial tissue in its filamented "hyphal" form, which is implicated in pathogenic infections", explains Weiner. Obtaining the ATIP-Avenir funding with which he set up his own research group in October 2018 has been the crowning achievement so far in a career in which he has acquired both the technical and biological expertise needed to address hitherto unanswered questions.
Combining innovative approaches
"My PhD, which I did at the Weizmann Institute of Science in Israel, concerned a highly innovative electron imaging technique known as volume electron microscopy, which I was one of the first in the world to apply. With this technique, we can obtain images of very large cell volumes with nanometric resolution", details the young team leader. Collaborations with other teams then allowed him to apply this technology to studying the Plasmodium falciparum parasite, implicated in malaria. Following this methodological research, Weiner joined Jost Enninga’s team at Institut Pasteur, where he did his first postdoc internship, concerning the Shigella and Salmonella bacteria. "The team’s expertise in fluorescence imaging and cell biology enabled me to set up a correlative pipeline – in other words, superimpose images of living cells obtained by fluorescence microscopy during infection, with images obtained by volume electron microscopy", specifies Weiner. With this approach, he was able to show the involvement of a specific cell compartment, the "macropinosome", in the first hour of infection with Shigella and Salmonella.
Developing his own vision
It was this combined experience in microscopy and microbiology, in the earliest aspects of bacterial infection and based on the C. albicans model, which convinced the ATIP-Avenir Program jury. "A number of teams are using mass cell analysis techniques to study the first stages of Candida albicans infection. My group wants to take things further by studying the question at individual cell level, which requires a high level of technical expertise", adds Weiner.
The new team, which also includes a postdoc researcher recruited thanks to the ATIP-Avenir funding, has set up in the Center for Immunology and Microbial Infection (Cimi-Paris) – an environment "at the cutting edge of cell biology and infectious diseases". In addition to funding the establishment of his laboratory and the improvement of a direct imaging installation, "the ATIP-Avenir Program has really enabled me to become independent very soon after my postdocs and to develop my own vision which has matured over the course of my previous projects. As a young researcher, it is an opportunity that I was delighted to be able to find in France and which also corresponds to the Israeli model in which I was educated", emphasizes Weiner.
Allon Weiner leads the Dynamics, Structure and Molecular Biology of Fungal Invasion team in the Center for Immunology and Microbial Infection (Cimi-Paris, unit 1135 Inserm/Sorbonne Université, Dynamics, Structure and Molecular Biology of Fungal Invasion team).