Current group members
I obtained my Master in Biology at the University of Geneva, working in the laboratory of Prof. Katharina Strub on Alu sequences and RNA-protein interactions, in the Cell Biology Department. I then wanted to focus on host-pathogen interactions, since I have always been fascinated by bacteria and how the host cell fights the infection. I therefore joined the lab of Thierry Soldati for my PhD in 2013, as part of the “International PhD Program in Basic and Applied Molecular Life Sciences”.
Understanding the role of vacuolins and their possible partners in the biogenesis of the Mycobacterium niche, and RNA-seq as a high throughput tool to monitor the transcriptional response during infection
Vacuolins are closely related to the mammalian flotillin/reggie proteins, which were shown to be involved in diverse mechanisms, such as the translocation of Glut4 transporters to the plasma membrane and more recently in E-cadherin and TfR recycling. Reggies/flotillins were also shown to interact with Rab11 and SNX4, known to be involved in recycling. In the lab, I am investigating the role of vacuolins and their possible partners in Dictyostelium, in the specific context of an infection with Mycobacterium marinum, a close cousin of the human pathogen Mycobacterium tuberculosis. Using my experience with RNA, I am also working in setting up an RNA-sequencing-based method to monitor the transcriptional response of both the host and the pathogen during an infection. We will then use this method to characterize the putative modes of action of different compounds identified by the drug screening and that have an effect during the infection, by comparing the transcriptional profiles.
Elena Cardenal Muñoz
During my degree in Biology I was always interested in Microbiology and Cell Biology. I did my PhD in the laboratory of the Prof. Ramos-Morales (University of Seville, Spain), where I was studying the host-pathogen interactions in the Salmonella and mammalian host cells model. There, by genetic and biochemical approaches, I analysed the S. enterica effector protein SteA to try to fully understand its role during the pathogenesis of epithelial cells and macrophages. I chose the Soldati group because I firmly wanted to continue analysing host-pathogen interactions, in this case with the Dictyostelium - Mycobacterium marinum infection model.
Role of TOR in immunity against mycobacterial infection
Dictyostelium is a social amoeba that feeds by phagocytosis and has a rudimentary but highly conserved cell-intrinsic immune system. It is genetically and biochemically tractable and has emerged as a powerful and experimentally versatile model organism. In addition, in recent years Mycobacterium marinum has emerged as a strong alternative model for tuberculosis research. It is a close cousin to M. tuberculosis and naturally causes a tuberculosis-like disease in fish and frogs. M. tuberculosis and M. marinum use similar strategies to interfere with the phagosome maturation programme and escape killing in both macrophages and amoebae. My main goal is to elucidate the putative role of TOR (target of rapamycin), the main kinase regulating cell growth and autophagy in eukaryotes, during mycobacterial infection. It is known that M. tuberculosis is controlled by autophagy and that, at the same time, more virulent mycobacteria are able to defend themselves against the autophagic process by activating TOR. Taking advantage of our Dictyostelium-M. marinum model, I want to study whether and how the bacterium leads to a TOR response to survive and proliferate inside Dictyostelium and, if so, how that response affects growth and phagocytic host rates and thus its immune response.
I read Biology at the University of Geneva where, after being awarded an Excellence Master Fellowship grant, I performed a MSc
with option 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 further the insights on the early effectors involved in Dictyostelium discoideum (Dicty) cell-autonomous defense response against pathogenic bacteria.
I am interested in Dicty’s early response factors involved in pathogen detection and stress signal transduction. Presently, I am gearing up to address Dicty factors involved in pathogen detection and stress signal transduction. For this, I will start by identification of the sub-cellular location of candidate factors through the GFP-tagging approach and live confocal microscopy. In a complementary study, employing a proximity-dependent biotinylation technique, ubiquitin-ligase complexes co-localizing with bacteria containing vacuoles, will be used as a “Trojan horse” in order to spot neighboring upstream and downstream acting factors. In addition, I will analyse on a genome-wide scale RNA-seq-generated expression patterns of various Dicty strains, in different conditions, shortly after the onset of infection with different pathogen strains. The goal would be to develop models in which the addition, the removal or the interaction of various host and pathogen factors would allow to predict in silico the outcomes of infections holding complex, not intuitive mechanisms.
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.
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.
I graduated from the University of Grenoble, France, with a Biology Master in Immunology, Microbiology and Infectious Disease. I did my internship at the Institute of Structural Biology with Dr Pascal Fender, and we focused on adenoviruses and their interaction with the Desmoglein 2 Receptor. I then wanted to go toward host-pathogen interactions in order to gain a better understanding of how the host cell can fight the infection. I therefore joined the group of Thierry Soldati for my PhD in September 2017, as part of the "International PhD Program in Life Sciences".
Single-cell dynamics of host-pathogen interactions
In the lab, we study the host and pathogen factors involved in mycobacterial infection by using the macrophage surrogate D. discoideum as a host. Intrinsic cellular defences play an important role during infection, and I am particularly interested by their roles in the establishment of the replication niche, its breakdown and the restriction of cytosolic bacteria. Furthermore, to get a deeper understanding of the mechanisms of mycobacterial infection, we need to characterize the infection process at the single cell level. This is why I am also studying the dynamics of the host-pathogen relation using a microfluidics system allowing the capture and observation of infected cell and a long-term integration and quantification of infection parameters.
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.
(1) Genome-wide characterisation of novel anti-tuberculosis compounds and study of their mode of action
(2) Image-based analysis of collective streaming behaviour in Dictyostelium
For my PhD, I wanted to bring together my two major scientific interests. I joined the group of Prof. Soldati to (1) discover novel active compounds against mycobacteria infections by using the amoeba D. discoideum as a 3R host model, and (2) to study the collective behaviour of D. discoideum during its developmental cycle. For the latter, I will collaborate with the group of Prof. Giovanna Di Marzo Serugendo (UNIGE), who is interested in bioinspired and autonomous algorithms.