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: Regulation and specificity of RNase H1/2 enzymes in stress and aging (m/f/d)
Activities and responsibilities
The research group of Jan Padeken offers the following PhD project:
An R-loop is an RNA-DNA hybrid that displaces the second DNA strand. R-loops occur frequently in genomes and have significant physiological importance, regulating gene expression and telomere stability. On the other hand, R-loops are a source of genomic instability e. g. in diseases associated with repetitive sequences including amyotrophic lateral sclerosis, Fragile X syndrome, Friedreich’s ataxia and trinucleotide repeat sequences.
Several pathways regulate the stability of R-loops. RNase H1 and RNase H2 are the central endonucleases that process RNA specifically in RNA-DNA hybrids. Loss of either enzyme results in an accumulation of R-loops and genome instability. Conversely overexpression of RNase H1 is frequently used to counteract the toxic effects of R-loop associated DNA damage. What regulates the role and activity of the RNase H1 and RNase H2 enzymes at “regulatory” and “toxic” R-loops is largely unknown. This is a central question in the field and mechanistical studies are complicated by the pleiotropic effects of the deletion mutants.
Interestingly C. elegans has four RNase H1 enzymesand a single RNase H2 enzyme. In this project we want to characterize these enzymes to understand:
1. Is there a natural separation of function for the RNase H1 enzymes?
2. How are the RNase H enzymes regulated during development, stress, and aging?
3. What is the binding specificity of the four different RNase H1 enzymes?
Initial data suggests that while 3 RNase H enzymes are ubiquitously expressed, two enzymes are differentially expressed in undifferentiated embryonic and germline cells compared to differentiated tissues. Interestingly, we see a strong upregulation of a subset of the RNase H enzymes in conditions known to trigger toxic R-loops, such as the aberrant expression of repetitive elements, or heat stress.
PhD project: Regulation and specificity of RNase H1/2 enzymes upon stress and aging
In this project you will use CRISPR to complete our existing collection of AID degron tagged strains. Using genomics and quantitative microscopy you will map R-loops, the RNase H enzymes, possible DNA damage and the effects on transcription, both upon degradation of specific enzymes and under stress conditions. Using C. elegans as a model we can correlate these molecular changes with stress resistance and aging of the organism.
We are looking for a highly motivated team player, interested in utilizing this unique opportunity to combine genome wide epigenetic profiling techniques with a CRISPR based screening approach and quantitative microscopy.
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 Padeken 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
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Advanced training in scientific techniques and professional skills
- Access to our state-of-the-art Core Facilities and their technical expertise
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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