PhD positions in Functional Genomics Group

Location: Ludwig-Maximilians-University Munich, Gene Center, Faculty of Chemistry and Pharmacy, Jae Group, Munich, Germany. Web: https://www.genzentrum.uni-muenchen.de/research-groups/jae/index.html

Project 1: Causes, Consequences and Correction of Mitochondrial Protein Misfolding

Mitochondria experience substantial stress and become dysfunctional with age and in age-related human diseases such as Parkinson’s. This typically involves the accumulation of misfolded proteins and toxic aggregates in the organelle. Surprisingly, mitochondria themselves do not encode any stress response genes and need to interface with the surrounding cell to combat such insults (Nature, 2020; Nature Comms., 2022, Mol. Cell, 2023). Despite intensive research in lower organisms, how mitochondrial protein toxicity arises and is sensed and combated in the human system is largely unknown. 

Your Mission:

You will harness bleeding-edge CRISPR genome engineering and genome-wide screening approaches to unbiasedly dissect how human mitochondria detect and fight aggregated proteins. Specific focus areas will be protein misfolding in the mitochondrial intermembrane space, where we have discovered novel proteostasis components, as well as signal transmission within and out of the organelle.  
This project is part of the new DFG priority program SPP2453 “Mitostasis” and will be conducted in close collaboration with the Max-Planck Institute of Biochemistry. As part of the priority program, you will be able to interact with interdisciplinary teams working on cutting-edge biological questions and participate in regular meetings and other proceedings, in addition to activities of QMB and the Gene Center Munich.

Project 2: Genetic Dissection of the Mitochondrial Integrated Stress Response (mitoISR)

Mitochondria are near-ubiquitous organelles that malfunction in aging and age-dependent human diseases. We have recently discovered a key signaling pathway that transmits mitochondrial stress to the cytosol in human cells: the mitochondrial integrated stress response (mitoISR). The central protein – DELE1 – acts as a sensor of protein import into the organelle that becomes active downstream of a wide range of mitochondrial insults (Nature, 2020; Nature Comms., 2022). Surprisingly, in unstressed cells, DELE1 is destroyed by the matrix-resident protease LONP1 (Mol. Cell, 2023). Mutations in LONP1 cause CODAS syndrome in humans. The role of the mitoISR in such disease scenarios and normal physiology is all but unknown.
This project will be conducted in collaboration with the excellence cluster Cellular Stress Responses in Aging-Associated Diseases (CECAD). As part of QMB and the Gene Center Munich, you will additionally have ample opportunities for scientific exchange with world-leading scientists of various fields and develop your scientific career with lasting benefits.

Your Mission:

You will utilize cutting-edge gene editing and genomics approaches to chart the genetic landscape of mitoISR signaling with a special focus on human disease variants. This will involve complex genetic interaction screening in human cells and elucidation of the underlying molecular mechanisms using a range of methodologies from synthetic biology to biochemistry and cell biology.

Your Profile:

Are you driven by a passion for science? Can you feel the thrill of discovering completely uncharted biology? Are you eager to make a meaningful impact on the world through biomedical research?  If you answered yes, then this opportunity at the Jae lab is for you.

Your Qualifications:

• Outstanding degree in a biomedical or related discipline
• Excellent communication skills and fluency in English
• Scientific precision, critical thinking and reliability
• Solid background in molecular biology, genetics and biochemistry
• Desirable: Prior experience with mammalian cell culture and gene delivery methods
• Desirable: Bioinformatics expertise (bash, SQL, python, R)

Our Offer:

You will be part of a dynamic and highly ambitious team in a brand-new research building with state-of-the-art lab space and excellent facilities. 

Application via the Graduate School Quantitative and Molecular Biosciences Munich (QMB):

As part of QMB, you will additionally have ample opportunities for scientific exchange with world-leading scientists of various fields and develop your scientific career with lasting benefits. The international PhD training program at QMB emphasizes communication and collaboration across traditionally separate disciplines, including biochemistry, medicine, bioinformatics, experimental and theoretical biophysics, and applied mathematics.

QMB places a strong emphasis on experimental work while also encouraging students to engage in theoretical approaches to derive meaningful insights from their data. This dual focus on advanced quantitative experimentation and theoretical analysis, combined with the excellence of its participating scientists, positions QMB uniquely within the European scientific landscape.

Please note: All applications have to be submitted in English through our online application tool. Applications submitted by mail or email will not be considered.

For detailed information about our application requirements see: https://qbm.genzentrum.lmu.de/application/requirements/ 

In your application, you can select up to two research groups you are interested in. For details about research areas and participating research groups, please see: https://qbm.genzentrum.lmu.de/research/research-areas-groups/