PhD position (Ageing & Disease/Epigenetics & Nuclear Dynamics): The role of cAMP for regulatory T cell homeostasis and function
Thinking of doing your PhD in the Life Sciences? The International PhD Programme (IPP) on Gene Regulation, Epigenetics & Genome Stability is offering talented students the chance to work at the cutting edge of research. 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.
Activities and responsibilities:
In the fields of “Ageing & Disease” and “Epigenetics & Nuclear Dynamics”, the IPP research group of Prof Tim Sparwasser offers the following PhD project:
Regulatory T cells (Treg cells) can be considered as the most important negative regulators of the immune system, balancing overshooting immune responses and preventing autoimmunity. Stability and function of Treg cells depends on continuous expression of the transcription factor Foxp3, which is controlled by epigenetic regulation as well as posttranslational modifications. The Foxp3 gene locus comprises 12 exons and four conserved non-coding sequence (CNS0 to CNS3) regions, which are located in introns near the promoter. Epigenetic modification of the Foxp3 gene was identified as the most reliant marker for stable expression: Demethylation of the Foxp3 promoter and highly conserved CpG islands in the CNS2 region, termed Treg cell-specific demethylated region (TSDR), were defined as a prerequisite for stable Treg cells. In addition, Foxp3 gene transcription is regulated by histone modifications, in particular acetylation and methylation.
PhD project: The role of cAMP for regulatory T cell homeostasis and function
The exact mechanisms how regulatory T cells (Treg cells) suppress are still an area of intense research. Elevated levels of cyclic adenosine monophosphate (cAMP) are considered to be essential for many suppressive effects on effector T cells (Teff cells) and antigen presenting cells (APC). We could demonstrate that Phosphodiesterase 3B (PDE3B), an enzyme degrading cAMP and a known target of FoxP3, is highly upregulated in non-functional Treg cells from scurfy mice leading to reduced cAMP levels and a loss of suppressive function. In addition, we identified a Treg cell-specific miRNA cluster targeting Pde3b in mice and humans implying PDE3B as an important regulator of Treg cell function. cAMP acts via a potent transcriptional inhibitor, inducible cAMP early repressor (ICER), a molecule also highly expressed by Treg cells. To specifically address the role of cAMP for the suppressive function of Treg cells we plan to study the importance of this pathway using tissue-specific conditional knock-out mice. We would like to understand the in vivo function of this pathway for regulating inflammatory diseases such as colitis and experimental autoimmune encephalitis and dissect the links between mitochondrial metabolism and anti-inflammatory immunity.
What we offer:
Are you an ambitious, young scientist looking to push the boundaries of science while interacting with colleagues from multiple disciplines and cultures? Then the IPP is your opportunity to give your scientific career a flying start!
All you need is:
For more details on the projects offered and how to apply via our online form, please visit https://www.imb.de/phd
The deadline for registration is 26 November 2021. Interviews will take place online 17-19 January 2022.
Starting date: 1 March 2022 – 1 September 2022
Tagged as: Life Sciences
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