PhD Biochemistry - Epigenetic Changes, Dendritic Cells (m/f/d)

Ort: Bretzenheim

Unternehmen: Institute of Molecular Biology gGmbH

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. 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.

In the field of "Ageing & Disease", the research group of Johannes Mayer offers the following PhD project: Inflammaging is observed in many tissues of ageing individuals in the absence of overt infection and contributes to the development of autoimmunity and other age-related pathologies. Low-level chronic production of pro-inflammatory cytokines, together with a dysregulated cellular metabolism, senescence, accumulating DNA damage and increased oxidative stress are considered main drivers of this response. Inflammaging is mainly driven by innate immune cells that reside in ageing tissues and thus affect intrinsic immune cell function, immune cell recruitment but also signaling to adaptive and non-immune cells.

While inflammaging has been well studied in the context of tissue-resident macrophages, these changes do not fully explain the changes observed in T cell mediated autoimmunity. We hypothesize that other Antigen-presenting cells are also epigenetically affected during ageing and that changes in tissue-specific Dendritic Cell differentiation or function play an important role in the development of local autoimmunity.

PhD Project:

"Epigenetic Changes Influence the Function of Dendritic Cells Throughout Life and Enhance the risk of Autoimmunity"

In this research project, we aim to investigate changes within Antigen-presenting cells in ageing tissues. While our research here in Mainz will focus on the development of skin and intestinal autoimmune diseases such as bullous pemphigoid, psoriasis and IBD, we will work closely with researchers from the FOR 5644 Initiative focusing on poorly understood reproductive and fat tissues. The goal of this project is to study the interplay between the ageing innate and adaptive immune system with a focus on tissue-specific dendritic cell subsets, Tregs and stem cell 'ageing'.

Advanced Immune cell isolation procedures, their cellular characterization by high-dimensional flow cytometry and single-cell RNA and ATAC sequencing, as well as molecular techniques to study genomic stability and intracellular signaling are therefore essential tools for this project.

As we could previously show that specialized subsets of Dendritic cells in healthy skin from young mice imprint a unique local immune environment, which is anti-inflammatory and linked to wound healing, we think that the opposite is true for Dendritic Cells in old mice and humans. On the one hand our preliminary data suggest that anti-inflammatory Dendritic cells subsets are decreased in aged skin, but also show that Dendritic Cells undergo molecular changes overall, which might impact their functionality, leading to a more pro-inflammatory immune environment.

We now want to understand if changes within the local microenvironment of ageing tissues are responsible for local Dendritic Cell reprogramming or if accumulating epigenetic changes in stem cells lead to distinct Dendritic Cell systemically. Furthermore we are interested to find out how human and murine Dendritic Cells from young and aged individuals differ functionally and how this impacts Treg function and T cell-mediated autoimmunity.

If you are interested in this project, please select Mayer_AGE as your project preference in the IPP application platform. Please note that this project is currently awaiting DFG approval, but funding for the first 2 years is guaranteed.

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 190 PhD students from 44 different countries.

For more details on the projects offered please visit www.imb.de/phd. The deadline for applications is 8 November 2023. Interviews will take place at IMB in Mainz on 22-24 January 2024. Starting date: 1 March 2024 - 1 August 2024.