Thinking of doing your PhD in the Life Sciences? The International PhD Programme (IPP) Mainz is offering talented 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: Immune cell function are heavily dependent on external signals. In most immunological studies the focus lies on biological molecules like antigens, cytokines, chemokines, growth factors, etc., while physical and chemical changes are often neglected. However changes in pH, salt and other ions, as well as physical changes such as tissue stiffness are drastically different between tissues in homeostasis and disease and can impact immune cell functions. Especially infiltrating immune cells such as T cells and myeloid cells are exposed to these changing microenvironments, which might results in context specific functionality. Especially in the context of the tumor microenvironment functional changes related to pH, salt and tissue stiffness have been associated with reduced immune cell functionality in T cells, while other cell populations have not been studied extensively. Our previous work has shown that dendritic cells, which stochastically reach all tissues, including tumors, have distinct tissue specific phenotypes. Similarly, other myeloid cells such as monocytes and macrophages adapt to their local micromilieu. We therefore hypothesis that these changes are, at least in part, determined by the different physical and chemical microenvironment they encounter and leads to functional changes that result in distinct T cell activation profiles. PhD project: Physical and chemical changes within the microenvironment affect antigen presenting cell function Within this project we have three sub-aims: Aim 1: Develop in vitro models to study the effects of pH, gas levels, salt and other ions, as well as tissue stiffness/pressure in monocytes, macrophages and dendritic cells Aim 2: Identify the molecular sensing machinery of physical and chemical changes in antigen presenting cells and selectively impair these mechanisms Aim 3: Study the role of sensing physical and chemical changes in the physiological microenvironment by comparing the cellular functionality of modified antigen presenting cells in different tissues and tumors This project utilizes immortalized cell lines, freshly generated primary immune cells from murine bone marrow, as well as in vivo models of cancer, to identify a fundamental biological sensing mechanism in immune cells and assess its relevance in disease. In Aim 1 you will develop strategies to study the effects of pH, gas levels, salt and other ions, as well as tissue stiffness/pressure in monocytes, macrophages and dendritic cells. Many protocols already exist to study these changes in T cells and you will translate them to study immortalized and primary myeloid cells (generated from murine bone marrow progenitors) and their morphological, phenotypical and functional changes. Through these experiments you will become an expert in immunological techniques, such as high-dimensional flow cytometry, RNAseq and T cell cocultures, which represent key expertise of our lab. In Aim 2 you will apply molecular techniques, such as western blotting, co-IP and KO-generation to identify the molecular sensing machinery of physical and chemical changes in antigen presenting cells and selectively impair these mechanisms. Being highly knowledgeable in these molecular techniques is therefore a pre-requisite for this project. In Aim 3 you will use these findings to study the role of sensing physical and chemical changes in vivo and compare the cellular functionality of modified antigen presenting cells in skin and tumors. If you are interested in this project, please select Mayer (APC) as your project preference in the IPP application platform. Are you an ambitious 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 For more details on the projects offered and how to apply via our online form, please visit www.imb.de/phd. The deadline for applications is 24 October 2024. Interviews will take place at IMB in Mainz on 20-22 January 2025. Starting date: 1 March 2025 - 1 July 2025