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 within the open call on “Molecular Mechanisms in Genome Stability & Gene Regulation”. 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.
PhD Position: R-Loop formation, alternative polyadenylation and secretory protein function (m/f/d)
Activities and responsibilities
The research group of
Sven Danckwardt offers the following PhD project:
Alternative polyadenylation (APA) is a widespread and highly dynamic mechanism of gene regulation. It affects more than 70% of all genes, resulting in transcript isoforms with distinct 3’end termini (Derti et al. 2012). APA thereby considerably expands the diversity of the transcriptome 3' end, leading to mRNA isoforms with profoundly different physiological effects, by affecting protein output, production of distinct protein isoforms, or modulating protein localization (Mayer, 2017). APA is globally regulated in various conditions, including developmental and adaptive programs (Tian & Manley, 2017). Perturbations of APA can disrupt biological processes, ultimately resulting in devastating disorders including cancer (Ogorodnikov et al. 2018, Nourse et al. 2020). Although substantial evidence for an interplay between RNA cleavage and polyadenylation (CPA) and the maintenance of genome stability exists (Spada, Luke, Danckwardt 2022, Khan & Danckwardt 2022), little is known about the role APA and CPA have in R-loop formation, and vice versa.
PhD Project: Functional implications of the crosstalk between R-loop formation and alternative polyadenylation In a systematic large-scale RNAi screening, we recently mapped the dynamic landscape of APA after depletion of >170 proteins involved in various facets of transcriptional, co- and post-transcriptional gene regulation, epigenetic modifications and further processes (Ogorodnikov et al. 2018, Marini et al. 2021). We observed that key components pervasively regulating CPA and APA (including RNA processing factors involved in the coupling of transcription termination and CPA such as PCF11) control processing of various components involved in the formation and resolution of R-loops (TREND-DB atlas
http://shiny.imbei.uni-mainz.de:3838/trend-db/).
In this project, we aim to investigate the crosstalk between R-loop formation and alternative polyadenylation, and how this contributes to R-loop homeostasis and modulation of CPA and APA, respectively. Our primary goal is to elucidate the underlying molecular mechanism(s) and to explore how these affect disease phenotypes.
This project will be part of the RTG on R-loop Regulation in Robustness and Resilience (4R).
If you are interested in this project, please select
Danckwardt (Rloop) 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 of more than 200 PhD students from 44 different countries
For more details on the projects offered and how to apply via the "Apply Now" Button.
The deadline for applications is 24 October 2024. Interviews will take place at IMB in Mainz on 20-22 January 2025.
Starting date: 1 March 2025 - 1 July 2025