Thierry Soldati

Current group members

Lyudmil Raykov

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Bio

I read Biology at the University of Geneva where, after being awarded an Excellence Master Fellowship grant, I performed a MSc opting in Genetics, Development and Evolution in the Department of Molecular Biology. There, as a member of David Shore’s Laboratory, using the budding yeast as a model system, I studied the nucleosome dynamics in growth-related gene promoter regions. In 2016, immediately after earning the MSc, I joined the group of Thierry Soldati engaging in a PhD research project with the aim to elucidate effectors involved in membrane damage repair and xenophagy induction using as a model the professional phagocyte Dictyostelium discoideum. After completion of my PhD thesis in 2020 I continued as a postdoc in the Soldati lab where I continued to work on the aforementioned project and in April 2023 published my study entitled "A TRAF-like E3 ubiquitin ligase TrafE coordinates ESCRT and autophagy in endolysosomal damage response and cell-autonomous immunity to Mycobacterium marinum." in eLife.

Current project

Currently one of my projects is to decipher the mechanisms by which infection with the pathogenic M. marinum delays D. discoideum cell cycle. Briefly, to address this question I resort to different approaches such as RNA-seq data analysis, in order to reveal gene sets involved in cell cycle regulation, DNA damage and checkpoint control, that are misregulated during the time-course of the infection. Complementarily, I monitor endogenous expression of the DNA damage reporter Rad51 during infection by flow cytometry, high-content microscopy or spinning-disk confocal microscopy. In parallel, I am engaged in a collaborative project aiming to identify conserved innate-immunity genes that D. discoideum shares with phyla ranging from Plants to Metazoa. Finally, I perform long-read sequencing analysis with various lab-related applications such as plasmid sequencing, D. discoideum or M. marinum genomic DNA sequencing, base-calling, quality control, filtering, genome assembly, establishment of consensus sequences and error correction.


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Nabil Hanna

Bio

I pursued a M.Sc. in clinical microbiology during which my major research focus was the identification of virulence genes and characterization of antibiotic resistance in H. pylori. The major focus of my thesis and my first postdoctoral studies was to characterize bacterial pathogenesis in Brucella. I did a second postdoctoral study at the EMBL were my research focused on the molecular and biochemical characterization of a post-translational modification in M. tuberculosis.

Current project

Characterization of anti-microbial target pathways in Mycobacterium using NGS techniques

I joined the Soldati group in November 2016, and I am interested in the characterization of anti-infective drugs against mycobacteria using high throughput NGS techniques. Dual RNA-sequencing is used to decipher a signature of the global state of the host-pathogen system. Specifically, our aim is to obtain full transcriptional profiles of Dictyostelium interacting with M. marinum and with anti-infective compounds. Once the putative mode of action identified, we will validate the major pathways of drug interference with infection by using a palette of standard biological assays.


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Jahn Nitschke

Bio

I obtained my BSc and MSc at the University of Konstanz (DE). I worked at the Human and Environmental Toxicology group of Prof. Daniel Dietrich, where I focused on microcystins, a family of potent liver toxins produced by cyanobacteria and a potential threat to many water supply systems. Throughout my master’s studies I also worked in the Neurobiology lab of Dr. Einat Couzin-Fuchs and the MPI for Ornithology on active sensing in cockroaches, which propelled my enthusiasm for computer-aided workflows.

Current projects

In my PhD project I work in a multidisciplinary consortium project that brings together phytochemistry, lipid metabolism, medicinal chemistry and infection biology. We exploit the largest private botanical collection of the French cosmetics and pharmaceuticals company Pierre Fabre to find natural products that help host cells to clear intracellular mycobacteria. With my work I hope to contribute to paving the way towards new approaches in the combat against mycobacterial diseases.


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Angélique Perret

Bio

After working on an acido-resistance system in Brucella microti and on the diversity of marine amoeba and their association with bacteria, I started an MSc in Microorganism-Host and Environment Interaction. During my first year, I completed an internship at the IRIM-CNRS, in Montpellier (FR), where I studied the role of phosphoinositides in the infection by the pathogenic intracellular bacterium Coxiella burnetii. Thus, I developed a strong interest for bacterial infection and their intracellular development. To continue in this field, I joined the group of Thierry Soldati to work on Mycobacterium marinum infection.

Current project

To study M. marinum infection the lab uses the social amoeba Dictyostelium discoideum as a model. Using this infection model, the role of vacuolins (homologues of the mammalian flotillins) was investigated and it was found that these host proteins are important for the infectious cycle of the bacteria. Along this line, the aim of my Master project is to compare the process of M. marinum infection in D. discoideum and BV-2 murine microglial cells. First, I will aim at confirming the role of flotillins in the infection of BV-2 cells and, in a second part, I will characterise the maturation of the Mycobacterium-Containing Vacuole in BV-2 cells compared to the MCV in Dictyostelium.


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Davide D'Amico

Bio

My interest in scientific research emerged during the period of my degree in Molecular and Cellular Biotechnology at University of L’Aquila (Italy). I started an internship for my Master’s degree project at Telethon Institute of Genetics and Medicine in Pozzuoli (Naples), in the lab of Prof. Maria Antonietta De Matteis, where I worked on a research project focused on the biogenesis of cellular stress granules with Sodium Arsenite as cellular stress inducer, analyzing the response of the secretory pathway COPII and the The TRAnsport Protein Particle (TRAPP), implicated in many human diseases. I joined the group of Prof. Soldati for my PhD because the use of D. discoideum as model host organism has a wide range of applications, many fundamental signal transduction pathways are shared with mammals and it’s an excellent platform to study membrane organization status, intracellular trafficking and signalling outcomes.

Current project

The role of the D. discoideum discoidins during M. marinum infection

Galectins are a family of 15 mammalian lectins with affinity for β-galactoside sugars that share a characteristic carbohydrate recognition domain and functions in signaling and endocytosis. Some galectins recognize the surface of various pathogens and have been proposed to have a direct antibacterial effect. In D. discoideum only discoidins share molecular and biological characteristics with galectins and they recognize self and non-self-glycoconjugates. There are two discoidin proteins, DscI and DscII, which share 48% sequence identity. DscI comprises three isoforms (DscA, DscC and DscD), whereas DscII has only one isoform (DscE). Discoidins are localized to the vicinity of pathogenic mycobacteria and required the induction of damage in the MCV membrane, which suggested a role during infection. For my PhD I would like to deepen further the Host response to vacuolar escape and better dissect the role of discoidins in the autophagic pathway.


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Céline Michard

Bio

I obtained a PhD in the host-pathogen interactions field from the University Lyon 1 in France. My PhD works discovered one of the targets of the LegK2 protein kinase, a Legionella pneumophila effector secreted in the host cell during infection. I then joined the Agaisse Lab in Charlottesville (USA) for a post-doctorate on the characterization of Shigella flexneri dissemination mechanisms. One of my projects explored the host side, studying the role of the mammalian protein WIPF2, whereas my other project focused on a Shigella effector. To continue to increase my knowledge in the host-pathogen field, I joined the Soldati group in March 2020 for a new post-doctoral study.

Current project

Mechanistic aspect of host membrane repair during mycobacterial infection

My project focuses on the membrane damage/repair step occurring during mycobacterial infection. During MCV establishment, the vacuole undergoes several damage events and repair of damage is a crucial step for a successful infection. The team previously showed that the autophagy and the ESCRT system are two pathways involved in this mechanism but the interplay between them is not yet understood. My aim is to elucidate the interplay between autophagy and ESCRT upon MCV damage, as well as to identify the bacterial components generating damage. The signaling cascade triggered by these events will also be explored.


Mélanie Foulon

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Bio

After a MSc in fundamental microbiology in Rennes (France) and several internships in Research laboratories (INRA, Pasteur Institute), I started my PhD in the team of Estelle Marion and Laurent Marsollier in Angers by the end of 2017. Here, I discovered the mycobacteria, and more specifically Mycobacterium ulcerans, the etiological agent of Buruli ulcer, a neglected tropical disease. My work focused on the virulence factor of M. ulcerans, a lipid-like toxin called mycolactone, and its involvement during the most advanced stages of the disease. The major aim of my PhD was to characterize the role of the inflammatory

 response of the host in response to M. ulcerans and its mycolactone.

Current project

Host-derived lipids: transport and utilization by mycobacteria during their intracellular life

Highly motivated by the study of host-pathogen interactions in the context of mycobacterial infections, and seeking to dissect deeper the underlying molecular and cellular mechanisms, I joined the Soldati team in January 2021 as a post-doctoral fellow. My project will focus on the dynamics of host-derived lipids association with M. marinum during infection using the Dictyostelium discoideum model. Mycobacteria have the unique ability to utilize host lipids to survive and proliferate. In that context, my aim will be to decipher the impact of lipid transport and utilization on their intracellular life, from the early stages of phagocytosis to replication and dissemination of the pathogen.


Sandra Guallar-Garrido

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Bio

I graduated in Bsc Microbiology and MSc Applied Clinical Research in Health Sciences at the Autonomous University of Barcelona (UAB) in Spain. After some research internships in Barcelona (Spain) and Cork (Ireland), I started my PhD under the supervision of Dr Esther Julián at the Mycobacteriology laboratory at UAB. There, I analysed determinant factors of the antitumor activity triggered by mycobacteria. Specifically, I studied the influence of culture media on the antitumoral effect of Mycobacterium bovis BCG and Mycobacterium brumae in the context of bladder cancer. Parallelly to my thesis, I did a successful collaboration to establish the bladder cancer model in CIC biomaGUNE (Donosti, Spain). Finally, during my PhD, I did a short-term stay at Université de Genève under the supervision of Dr Thierry Soldati, where I discovered the amoebae model as a model to study host-pathogen interactions.  

Current project

Since I started my career, I became fascinated by the constant evolutionary race of hosts and pathogens that drove to highly complex interactions between them. Therefore, after discovering the Dictyostelium discoideum-Mycobacterium marinum model, I joined the Soldati lab for my postdoctoral stay. In my present project, I am interested in studying the conserved machineries responsible for sensing membrane damage inflicted by sterile or mycobacteria-derived agents, as well as the subsequent coordination of repair and restriction of infection. To assess this, I will decipher the pathways of TrafE regulation, an evolutionary conserved TRAF6 homolog that has recently been identified as the likely coordinator between autophagy and ESCRT machineries. 


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Bio

I obtained my BSc in Chemical Engineering at Polytechnic Institute of Bragança (IPB) in Portugal and I started the MSc in Biochemistry at University of Geneva. I joined the group of Thierry Soldati in July 2022, for a summer internship, to gain insight in cellular and molecular biology, by using  Dictyostelium discoideum. After completing the internship, I developed an interest for the host-pathogen interaction field, therefore, I decided to continue with the group for my master project.

Current project

Role of lipophagy during Mycobacterium marinum infection in Dictyostelium discoideum

The  host lipids are a source of nutrients and energy for Mycobacteria. The group uses D. discoideum-Mycobacterium marinum as model system to gain insight of how the host-derived lipids are access, import and used by mycobacteria. The access of the host-derived lipids might be mediated by lipophagy, microautophagy or fusion-like processes. The focus of my  master project is to study the mechanism involved in the recruitment and translocation of autolipophagosomes to the Mycobacterium-Containing-Vacuole (MCV). Also will be studied the impact in the MCV compartment and on the mycobacteria growth.


JUSTINE TOINON

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Bio

During my MSc in Genetics and Cell Biology, with an option in infectious disease at the University of Lyon, France, I performed an internship in Research & Development at Sanofi in Marcy l’Etoile, France. My research focus was the determination of the transport of a new antibiotic in Gram-negative bacteria. I then joined Lionel Navarro's Lab at the “Institut de l’Ecole Normale Supérieure de Paris” (IBENS, France). My PhD work focused on the identification and characterization of an RNA silencing suppressor from the human pathogenic bacterium Legionella pneumophila.

Current project

Strongly interested in the study of host-pathogen interactions and the regulatory mechanisms orchestrating immunity, I joined the Soldati group in March 2023 as a post-doctoral fellow. My major focus will be to explore the signaling cascades and transcriptional reprogramming in the course of Mycobacterium marinum infection both in Dictyostelium discoideum and in murine microglial cells, enabling the orchestration of the cell-autonomous defense pathways during infection.


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Bio

In 2017, after obtaining my BSc. in Biology at Unicamp (Campinas/SP - Brazil), I started my PhD in Genetics and Molecular Biology at the same institution, supervised by Prof. Cristina Alvarez-Martinez. There I worked on the characterisation of the anti-amoeba T6SS of Xanthomonas citri, focusing on the identification of secreted effectors and their recruitment mechanism. As part of a collaborative effort, I joined the Soldati lab for a 3-month internship to evaluate the effects of ectopic expression of putative X. citri T6SS effectors (T6SE) in D. discoideum and to develop a tool to monitor the translocation of the T6SE from X. citri to D. discoideum in vivo. In March 2023, I returned to Geneva as a postdoctoral fellow in the Soldati group.

Current project

X. citri - D. discoideum interaction

Xanthomonas citri is a plant pathogenof major importance, affecting citrus production worldwide. Although several groups are working to decipher the mechanisms involved in the virulence and pathogenesis of this bacterium, aspects related to its survival in the environment have been less studied.In collaboration with the group of Prof. Cristina Alvarez-Martinez in Brazil, my project will focus on elucidating the strategies used by X. citri to resist predation by our favorite beast, the bacterivorous amoeba D. discoideum. My main aim is to understand the dynamics of the interaction between these two microrganisms, a hitherto unexplored aspect of xanthomonads, and to build a comprehensive atlas of the events that occur when X. citri meets Dicty.

autonomous defense pathways during infection.


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Bio

Before starting my Master's degree in Health Biology, option infection Biology at Montpellier, France, I obtained a Bachelor's degree in life sciences, option neurobiology, physiology and biochemistry in Nice, France. After several internships in infectiology, I joined the SOLDATI team at the beginning of February 2023 for a 6-month master 2 internship. This internship will allow me to learn more about Mycobacteria virulence mechanisms using Dictyostelium discoideum as a hostmodel, which will also improve my skills in molecular and cellular biology.

Current project

During intracellular infection in Dictyostelium discoideum, Mycobacterium marinum resides in a Mycobacteria containing vacuole (MCV). Like Mycobacterium tuberculosis, M. marinum uses different virulence factors within their host to survive and replicate. In particular, they secrete a pore-forming peptide called EsxA that is essential to damage the MCV membrane and escape to the cytosol. In order to study and better understand the role of this  effector in Mycobacterium marinum, I will replace it by various perforins from other bacterial pathogens. This strategy will allow us to study the secretion of these heterologous perforins and their potential function in MCV damage and cytosol escape during infection in Dictyostelium discoideum.