PhD position (m/f/d)
Mitochondrial RNA modification- driven metabolic plasticity in leukemic stem cells and drug resistance
wanted for the next possible date at the Department of Medicine V, Hematology, Oncology, Rheumatology.
For our project "Mitochondrial RNA modification- driven metabolic plasticity in leukemic stem cells and drug resistance" we are looking for a PhD student. The project is is part of the SFB/CRC 1709 "Cellular Plasticity in Myeloid Malignancies: From Mechanisms to Therapies”. In this CRC we will focus on myeloid malignancies as a model to dissect the various molecular mechanisms that enable and regulate cancer cell plasticity in AML. Our overall goal is to pave the way for new cancer therapies.
Mitochondria play a critical role in cancer progression by enabling metabolic adaptation in response to microenvironmental cues, contributing to tumor heterogeneity, metastasis, and drug resistance. Our previous work has shown that mitochondrial RNA modifications facilitate the translation of mitochondrially encoded genes, thereby promoting the metabolic flexibility of aggressive and treatment-resistant cancers, including acute myeloid leukemia (AML).This PhD project aims to uncover how mitochondrial RNA modification pathways regulate stem cell function and influence responses to anti-cancer therapies. To achieve this, we will apply cutting-edge technologies, including nanopore direct-RNA-seq. CRISPR pertubations in primary healthy and malignant cells, Ribo-seq, scRNA-seq, PDX in vivo models.
The PhD student will work closely together with a PhD student in the lab of Prof. Michaela Frye, which will focus on the in vivo experiements of the joint SFB/CRC.
- Job-ID: V000014502
- Field of application: Klinik für Hämatologie, Onkologie und Rheumatologie
- Location: Heidelberg
- Start date: 01.10.2025
- Job Category: Science and teaching
- Working hours: Part time (65 %)
- Published: 18.07.2025
- Limitation: Temporary (2 years with option of extension)
- Contract: TV-L
Your tasks
- Analyze tRNA modification levels in matched leukemia patient samples collected at diagnosis and relapse, and compare them to healthy hematopoietic specimens using nanopore-based direct tRNA sequencing. Complementary transcriptomic, proteomic, and metabolomic profiling will be performed on the same samples
- Integrate multi-omics data (e.g., using MOFA) to investigate how patient-specific tRNA modification patterns correlate with treatment response and survival
- Functionally validate candidate RNA modifications and their associated enzymes using CRISPR-Cas9 knockouts in both primary healthy and malignant cells, as well as established cell culture models
- Conduct colony-forming unit (CFU) assays, drug synergy screens, ribosome profiling (Ribo-Seq), and nanopore sequencing of modified primary cells and cell lines
- Work in close collaboration with a PhD student from the Frye Lab, particularly on in vivo models and single-cell RNA sequencing (scRNA-seq). Additional collaboration with other research groups within CRC/SFB 1709 is expected
Your profile
- Master degree (or similar) in molecular biology, biomedicine, biotechnology, bioinformatics or a related field
- Experience in molecular biology methods (e.g. PCR, NGS, cell culture) and/or functional cell assays
- Strong interest in cancer biology, RNA biology, and stem cell research
- Bioinformatics experience, e.g. R, preferred
- High motivation, curiosity, and the ability to work independently and in a team as well as good communication skills in english (written and spoken) are expected
We offer
- Goal-oriented, individual training and development opportunities
- Working with the latest techniques / technical equipment
- Possibility of doctorate
- Possibility to publish scientifically is offered and supported
- Regular team meetings
- Close collaboration within SFB/CRC1709
- Collectively agreed remuneration, attractive company pension scheme (VBL)
- 30 days vacation
- Sustainable travel: job ticket
- Family-friendly working environment: cooperative arrangements for childcare, subsidy for child vacation care, advice for employees with relatives in need of care
- Wide range of health, prevention and sports offers
Interested?
Applications will be accepted until 10.08.2025 direct online.
Klinik für Hämatologie, Onkologie und RheumatologieDr. Cornelius Pauli
