PhD position (Epigenetics & Nuclear Dynamics): Chromatin state dysregulation due to abnormal mitosis

Thinking of doing your PhD in the Life Sciences? The International PhD Programme (IPP) Mainz 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 field of “Epigenetics & Nuclear Dynamics”, the research group of Stamatis Papathanasiou offers the following PhD project:

Proper division of the genomic material is fundamental for cell homeostasis. Although cells have developed a plethora of mechanisms to ensure error-free division, mistakes during mitosis are common in normal physiology and a hallmark in disease. Such mistakes give birth to dysbalanced, aneuploid genomes. A prominent manifestation of mitotic errors is the generation of abnormal nuclear structures, such as micronuclei and chromosome bridges, common features of nuclear atypia in cancer with major physiological significance. Micronuclei are miniature, additional nuclei that form when a chromosome lags during mitosis and then recruits its own nuclear envelope. These structures accumulate massive DNA damage and can lead to severe rearrangements by mechanisms that are now starting to be understood. Yet, we do not fully understand the effects of dysbalanced genomes on cellular function and how these abnormalities contribute to disease initiation and progression.

We recently discovered a new phenomenon of heritable chromatin and transcriptional defects mediated by micronuclei. These alterations are inherited after the micronuclei reincorporate into the normal nuclear environment of daughter cells and are strongly associated with long-lived DNA damage. This work showed that chromosomal instability is inherently coupled to variation in gene expression, which may impact tumor evolution and provided significant insight into the elusive mechanisms leading to non-genetic, cell-to-cell epigenetic variability observed in pathophysiology.

PhD project: Chromatin state dysregulation due to abnormal mitosis

Under what exact circumstances cell division errors can give birth to massive DNA lesions and other chromatin alterations, their inheritance in the progeny and their functional significance remain a mystery. The potential involvement of additional mitosis-mediated mechanisms – other than micronucleation – that initiate cascades of non-genetic alterations is also a black box.

We are excited to welcome a PhD candidate to attack these questions. We will combine cutting edge techniques, such as targeted chromosome manipulation and gene engineering, with the development of advanced systems to track mis-segregated chromosomes by live-cell imaging over multiple generations. We will identify additional sources of inherited abnormal nuclear structures, investigate their DNA damage/repair dynamics and determine the immediate and long-term effects on these nuclear bodies’ epigenome.

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

What we offer:

• Exciting, interdisciplinary projects in a fully 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

Requirements:

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:

• Master or equivalent
• Interactive personality & good command of English
• 2 letters of reference

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 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