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-loops in cancer & cancer therapy (m/f/d)
Activities and responsibilities
The research group of Thomas Hofmann offers the following PhD project:
The PhD project is embedded in the 4R GRK dedicated to a better understanding of R-loop biology. R-loops are three-stranded RNA-DNA hybrids of an RNA that invades an DNA duplex and mainly formed in a co-transcriptional manner. Although R-loops fulfill beneficial regulatory functions in gene expression and telomere stability, unscheduled R-loop formation and/or persistence can drive replicative stress and genome instability by causing transcription-replication conflicts. Loss of tumor suppressors and activation of oncogenes is a hallmark of cancer and has been linked to increased transcription-replication conflicts and R-loop formation. Unscheduled R-loops activate the DNA damage signaling cascade and therefore establish specific sensitivity to DNA damage checkpoint kinase inhibition. Interestingly, potential links between numerous tumor suppressors and R-loops have not been addressed so far and thus remain unknown. In addition, also the potential to exploit such links as potential Achilles heel to specifically target cancer cells remains unclear.
PhD Project: R-loop regulation by tumor suppressors: an Achilles heel to target cancer cells?
Our unpublished data indicate that loss of a specific tumor suppressor (TS) gene results in an increased, unscheduled R-loop formation. The increased R-loop formation is linked to replication stress and activation of the DNA damage signaling network. Aim of this PhD project is to study the underlying mechanism of R-loops formation and its role in genome instability and cancer cell sensitivity to therapy by addressing the following scientific questions or applying the following methodology and techniques:
(1.) How does the loss of the tumor suppressor trigger increased R-loop formation and (2.) where in the genome do the R-loops arise (S9.6 Cut & Tag Seq)? (3.) Do we also find an increase in cytoplasmic R-loops and activation of innate immunity and the inflammatory response? (4.) Which negative regulators of R-loops (helicases, nucleases and RNA-binding proteins) are involved in balancing increased R-loop formation in cancer cells that lost this TS? (5.) Can we exploit the increased R-loop formation to increase sensitivity of cancer cells to therapy? The project will be performed in close collaboration with the Genomics core facilities at IMB and with colleagues of the 4R GRK.
If you are interested in this project, please select Hofmann 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, please visit
www.imb.de/phd.
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