Thinking of doing your PhD in the Life Sciences? The International PhD Programme (IPP) Mainz is offering talented, young scientists the chance to work on cutting edge research projects within the open call on “Molecular Biomedicine & Ageing”. As an IPP PhD student, you will join a community of exceptional scientists working on diverse topics ranging from how organisms age or how our DNA is repaired, to how epigenetics regulates cellular identity or neural memory. The research group of Johannes Mayer offers the following PhD project: Trained immunity has recently been discovered as a novel mechanism of immune cell memory in innate immune cells. Different to the adaptive immune system, innate cells do not develop into antigen-specific long lived memory cells that can be reactivated. Instead it was found that epigenetic and metabolic changes in stem cells and progenitors are transmitting previous information (e.g. from prior infections) and change the general activation status of future generations of innate immune cells. Especially monocytes have been studied in the context of trained immunity, but other cell types like neutrophils and even epithelial cells contribute to trained immunity. These changes provide a more effective response to similar threats in the future, linked to pattern recognition pathways and cytokine production. As this re-activation is not antigen specific, it can also be triggered in response to other stimuli, potentially leading to broader beneficial but also detrimental effects. While trained immunity is not as specific or long-lasting as adaptive immune memory it still provides a faster, more robust reaction upon re-exposure in a non-antigen specific context. PhD project: Trained immunity of dendritic cells In this PhD project we aim to study if dendritic cells also contribute to trained immunity in models of infection and inflammation. Dendritic cells play a fundamental role in antigen presentation and the priming of naive T cells. They are short lived and constantly replenished by stem cells within the bone marrow from where they are dispersed into tissues, to sample and recognize pathogens. Upon activation they rapidly migrate to the draining lymph nodes to activate T cells via antigen presentation, costimulatory marker expression and cytokine production. Several lineages of dendritic cells have been described, which perform enhanced roles for certain immune responses, as cDC1 preferentially control CD8 T cell responses via cross-presentation, while cDC2 are specialized in driving different T helper cell responses by producing key molecules for their differentiation. To study if dendritic cells also play a role in trained immunity, we will establish murine models of recurring inflammation and re-infection and use different single-cell and omics approaches established in our lab to characterize and define the cellular, molecular and functional changes of dendritic cells. These changes will be carefully compared to monocytes, which have been well studied in trained immunity. Furthermore, phenotypes of trained immunity between different dendritic cell lineages will be assessed. Due to their rapid activation and low frequency in tissues, the study of dendritic cells is challenging. Therefore this PhD requires a strong background in immunology, previous experience with complex phenotyping of immune cells by flow cytometry (10 markers) and previous experience with murine models of inflammation or infection. If you are interested in this project, please select Mayer (DCMem) as your project preference in the IPP application platform. Are you an ambitious, young scientist looking to push the boundaries of research while interacting with colleagues from multiple disciplines and cultures? Then joining the IPP is your opportunity to give your scientific career a flying start All you need is: Master or equivalent Interactive personality & good command of English 2 letters of reference Exciting, interdisciplinary projects in a lively international environment, with English as our working language Advanced training in scientific techniques and professional skills Access to our state-of-the-art Core Facilities and their technical expertise Fully funded positions with financing until the completion of your thesis A lively community of more than 200 PhD students from 44 different countries