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.
PhD Position: Immune cell exhaustion of antigen presenting cells in infection and cancer (m/f/d)
Activities and responsibilities
The research group of Johannes Mayer offers the following PhD project:
Immune cell exhaustion is a common phenotype in chronic infection and cancer and has been linked to the continuous exposure to antigens. While its mechanism is well understood in T cells, it is unclear if antigen presenting cells also undergo immune cell exhaustion and show reduced activation potential after continuous exposure to antigens.
Monocytes, macrophages and dendritic cells are the major myeloid cell populations involved in antigen presentation. They are also important cytokine producers and express an array of costimulatory molecules to activate and amplify adaptive immune responses. Monocytes, macrophages and dendritic cells possess a sophisticated machinery to take up and present antigens and many of their cellular functions are linked to the recognition of danger and pathogen associated molecular patterns. While many myeloid cell populations are short lived, recent findings show that innate immune cells also possess mechanisms for memory responses, leading to increased activity during secondary antigen challenge. We therefore hypothesize that these cells might also undergo immune cell exhaustion, resulting in reduced cellular activity, anergy and even cell death, and a suboptimal activation of T cells upon continuous exposure to antigens and plan to study this in the context of chronic infection and cancer.
PhD Project: Immune cell exhaustion of antigen presenting cells in chronic infection and cancerWithin this project we have three sub-aims:
Aim 1: Develop an in vitro model to study the effects of continuous antigen exposure in monocytes, macrophages and dendritic cells
Aim 2: Study mechanisms of trained immunity and immune cell exhaustion of antigen presenting cells in the context of chronic infection and cancer
Aim 3: Identify the molecular machinery of immune cell exhaustion in antigen presenting cells in comparison to exhausted T cells and develop treatment approaches
This project depends on freshly generated primary immune cells from murine or human blood and bone marrow, as well as in vivo studies using murine models, as immortalized cell lines insufficiently display immune cell exhaustion characteristics. This project aims to identify a fundamental biological mechanism in immune cells and assess its relevance in chronic infection and cancer models.
In Aim 1 you will become an expert in generating monocytes, macrophages and dendritic cells from primary murine and human material (mainly blood and bone marrow) and develop techniques to study the effects of repeated and continuous antigen exposure. Importantly, you will be tasked to extend the life span of these cells to study changes in antigen uptake, antigen presentation and cellular activation after repeated and continuous antigen exposure using molecular and imaging techniques.
In Aim 2 you will use high-dimensional flow cytometry and other omics approaches to study mechanisms of trained immunity and immune cell exhaustion of antigen presenting cells in the context of chronic infection and cancer. Here you will primarily focus on bone marrow progenitors and changes they undergo on a cellular, transcriptomic and epigenetic level and how these changes lead to a modified functional response in mature monocytes, macrophages and dendritic cells.
In Aim 3 you will use these findings to compare immune cell exhaustion in antigen presenting cells to exhausted T cells and identify treatment approaches that reverse immune cell exhaustion in both cell types.
If you are interested in this project, please select Mayer (Exhaust) as your group preference in the IPP application platform.
Qualification profile
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
We offer
- Exciting, interdisciplinary projects in a lively international environment, with English as our working language
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Advanced training in scientific techniques and professional skills
- Access to our state-of-the-art Core Facilities and their technical expertise
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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 the "Apply Now" Button.
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