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: RNA-DNA hybrid regulation in senescence and ageing (m/f/d)
Activities and responsibilities
The research group of Brian Luke offers the following PhD project:
RNA-DNA hybrids have important implications in the cell and play critical roles in processes like DNA replication, telomere elongation and transcription termination, not to mention CRISPR/Cas gene editing. RNA-DNA hybrids are primarily removed by the RNase H family of endonucleases. RNA-DNA hybrid misregulation has recently been strongly implicated in senescence, ageing as well as neurodegenerative diseases and cancer. When RNA-DNA hybrids (and R-loops) are not properly removed, they lead to severe genomic instability, increased rates of mutagenesis and inflammation. RNA-DNA hybrids can be formed as a by-product of transcription, however they are also formed during DNA replication, when the polymerases use RNA bases instead of DNA bases (NTPs instead of dNTPs). Very little is understood regarding how the RNase H enzymes are regulated and especially how RNA-DNA hybrids are regulated in aged and senescent cells and how this may influence the rate of aging and the prevalence of disease in aged, compared to young, organisms.
PhD Project: R-loop and rNMP regulation in ageing and senescence
It has recently been shown that the speed of transcription increases with age, and it was suggested that this may be responsible for some aspects of aging. Interestingly, transcription is responsible for the formation of R-loops (co-transcriptional three stranded structures with an RNA-DNA hybrid) as well as the mutagenesis of ribonucleotides inserted into the genome. This project will be performed in yeast and worms, as model systems, and will be comparing young and old cells. We will determine if R-loops and genomic ribonucleotides are age regulated and if so where in the genome this is occurring and why is the regulation different as we age. We will be employing RNA polymerase mutants that have increased and decreased rates of elongation and assay their effects on lifespan, ribonucleotide-associated mutagenesis and R-loop and ribonucleotide levels. Similarly, we will be trying to answer the same questions in senescent cells that are experiencing telomere shortening, as my lab has previously shown that short telomeres accumulate very stable R-loops. Finally, we be using interventions that are known to either extend or decrease lifespan to determine their effects on the RNA-DNA hybrid regulation during aging and senescence. Within this project students will use a host of molecular, biochemical, genetic and genomic approaches to tackle these questions. The answers to these questions will have important implications regarding aging and age-related disease.
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 Luke 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 our online form, 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