Research Team / Research Group Name (if any)
920685- Microorganism - host interaction. Human Proteome Project.
Brief description of the Research Team / Research Group / Department
In our group we are interested in the study of microorganism - host interaction from the perspective of proteomics. We are focus on the opportunistic pathogenic fungus Candida and on candidiasis. We aim to improve our knowledge on the molecular mechanisms of the host innate and acquired immune responses and also the pathogen processes of infection and virulence. Among our objectives we try to search novel biomarker and vaccine candidates for invasive candidiasis. But also, from the angle of the host, we are interested in the activation of signaling pathways in innate immune cells interacting with Candida cells.<br />We use Discovery Proteomics, to acquire an overview of the proteome Candida cells. Then focusing on a selected set of proteins of interest, we use Targeted Proteomics, which enables validation and quantitation for the target set with very high reproducibility and sensitivity. <br />We have a great interest in the study of particular proteomes with great potential clinical applications. In this respect we study the phosphoproteome; the surfome, i.e. the set of proteins present in the fungal surface which first contact cells of the host immune system; proteins present in secreted vesicles, and the set of proteins involved in apoptosis, since those would make an ideal target to selectively trigger this process.<br />We are also involved in the Human Proteome Project (HPP) focusing on missing proteins and proteins involved in the defense against infectious diseases.<br />
Research lines / projects proposed
Our research lines have as main purpose the study of C. albicans-host interaction, with the final goal of contributing with new strategies to fight against invasive candidiasis. We are interested in the study of C. albicans proteome along the interaction with macrophages and under oxidative stress conditions. We are focused on quantitative proteomics, protein complexes (Interactome) and posttranslational modifications of proteins (PTMs). Changes in phosphorylation and acetylation will be studied in depth, since they are some of the most relevant PTMs during cell signaling. These studies will be performed using Data Independent Analysis (DIA), which is an up to date proteomic technique that enables a high throughput analysis. <br />The proposed projects are:<br />1. Monitoring the changes in the phosphoproteome and acetylome during C. albicans-macrophage interaction and in the presence of H2O2 as apoptosis inducer. Mass spectrometry analysis, data mining and functional validation of the results. These results will shed light to C. albicans biology and to the signaling networks involved in its death, which could be applied for the design of new therapies<br />2. Global proteomic study in C. albicans after treatment with metformin, an oral antidiabetic drug that was recently found to have synergic antifungal activity with common antifungal drugs. Mass spectrometry analysis, data mining and functional validation of the results. <br />3. Study of C. albicans interactome, using native electrophoresis, mass spectrometry and machine learning will allow an integrated description of Candida cellular processes and of the important proteins involved in this response, including those with unknown function. Six hours of interaction with macrophages will be the selected condition for this study<br />