Time Span 01 Mar 2023 for 3 years Application Deadline 19 Nov 2022 Financing yes Type of Position
Field of Research
Subjects Molecular Biology Description 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 “Epigenetics & Nuclear Dynamics”, “Gene Regulation & Evolution”, and “Computational Biology”, 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: Genome architecture and transcription dysregulation due to abnormal mitosis How transcription is (dys)regulated in the context of mitotically-derived abnormal nuclear structures - or aneuploidy in general - is poorly understood. Another fascinating and understudied question is how genome organization is affected when these abnormal chromosomes reintegrate into the normal nuclei of daughter cells. An interested PhD student will take advantage and build upon novel methods we developed recently to spearhead the investigation of these questions, such as a new experimental and computational framework that links phenotype to function at the single-cell level (named “Look-Seq2”). We will study how transcription dynamics are perturbed in daughter cells upon abnormal mitosis and delineate the mechanisms of transcription dysregulation. We will also define how reincorporation of abnormal chromosomes from micronuclei and bridges into the primary nucleus affects genome organization by cutting-edge single-cell-based sequencing and imaging approaches in combination with genome engineering.
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 19 November 2022. Interviews will take place on-site in Mainz 16-18 January 2023. Starting date: 1 March 2022 – 1 July 2023
Language of Dissertation
More Information https: // www. imb.de/students-postdocs/international-phd- programme/apply-to-ipp/projects-offered/stamatis-papathanasiou-1