2 PhD positions (DNA Repair & Genome Stability; Epigenetics & Nuclear Dynamics): Epigenetic transgenerational inheritance of DNA damage (m/f/d)PhD - Individual Supervisor

Thinking of doing your PhD in the Life Sciences? The International PhD Programme (IPP) on Gene Regulation, Epigenetics & Genome Stability 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.

Activities and responsibilities

In the fields of “DNA Repair & Genome Stability” and "Epigenetics & Nuclear Dynamics"  the research group of Siyao Wang offers the following 2 PhD projects:

One fascinating aspect of biology is that an organism can develop two fundamentally distinct cellular programs - the somatic program and the germline program. Epigenetic modifications maintain the distinction between these programs. The somatic epigenome can dynamically change in response to endogenous and exogenous stresses and affects development and aging, while the germline epigenome remains repressed to ensure a stable genome for subsequent generations.

DNA damage poses a significant threat to genome stability, chromosomal integrity, and cellular function. Transcription-coupled nucleotide excision repair (TC-NER) defects can cause growth and mental retardation, photosensitivity, and premature aging in Cockayne syndrome (CS) patients. Chromatin serves as a platform for DNA repair and undergoes dynamic changes during the DNA damage response (DDR) through the Access-Repair-Restore model. Histones, an essential component of chromatin, are post-translationally modified via methylation, ubiquitination, and acetylation to regulate DDR-related chromatin functions. Many histone modifications leave long-term epigenetic memory in cells and can be transmitted across generations, raising the possibility that DNA damage can reshape the epigenome in damaged cells and affect their descendants.

PhD project 1: Transgenerational consequences of transcription-blocking DNA damage

Previously, we identified a specific role of a histone modification, histone 3 lysine 4 di-methylation (H3K4me2), in the recovery of gene expression following UV-induced transcription-blocking DNA lesions. Blocking the deposition of H3K4me2 by removing the H3K4 methyltransferase complex, MLL/COMPASS complex, resulted in developmental arrest and lifespan shortening after UV treatment. In contrast, elevating H3K4me2 through depleting the histone demethylase SPR-5, can accelerate development and extend lifespan upon UV damage. Specifically, we have demonstrated that the UV-induced H3K4me2 facilitates the transcriptional recovery of protein biosynthesis and homeostasis genes. Repressing protein biosynthesis by treating worms with a translational inhibitor can reverse the beneficial effect of elevating H3K4me2 deposition upon UV. This work highlights the significance of H3K4me2 in regulating the development and aging of somatic tissues following transcription-blocking DNA damage.

H3K4 methylation is well-known for its role in the transgenerational inheritance of longevity. However, whether DNA damage-induced epigenetic alteration can lead to a transgenerational effect is still unknown. This proposed project aims to investigate the transgenerational consequences of transcription-blocking DNA damage in cellular homeostasis and longevity in C. elegans.

If you are interested in this project, please select Wang (H3K4) as your group preference in the IPP application platform.

PhD project 2: Transgenerational epigenetic memory of paternal DNA damage

Recently, we identified a novel mechanism that underlies the transgenerational genetic and epigenetic effects of paternal DNA damage. Using sex-separated C. elegans strains, we found that paternal, but not maternal, exposure to ionizing radiation (IR) leads to transgenerational embryonic lethality. This lethality is caused by the persistence of DNA double-strand breaks (DSBs) in the F1 generation, where a highly enriched heterochromatin structure blocks the accessibility of homologous recombination (HR) repair machinery. This project will investigate how DNA damage in sperm alters the epigenome of the offspring, and whether these changes in the epigenome can affect genome stability and longevity of the subsequent generations. Via answering these questions, we aim to identify potential therapeutic approaches to improve the genome stability of the worms carrying paternally inherited DNA DSBs.

If you are interested in this project, please select Wang (paternal) 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

·       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 ofmore than 190 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 19 April 2023. Interviews will take place at IMB in Mainz on 19-21 June 2023.

Starting date: 1 August 2023 – 1 February 2024