PhD position Activity control of standalone bacterial AAA+ disaggregases (f/m/d)

The successful candidate will join the project group of PD Dr. Axel Mogk, renowned for his work on bacterial protein quality control systems.

The hexameric AAA+ proteins ClpG and ClpL function as superior protein disaggregases and provide extreme heat resistance to bacteria by reactivating aggregated proteins. They protect bacterial pathogens against temperature-based sterilization protocols, qualifying them as important persistence factors and potential drug target. Elucidating their regulatory and working mechanisms will provide important information for potential future drug development to inhibit or deregulate disaggregase activities. We want to dissect the molecular basis of ClpG and ClpL activity control. How is the activity of the disaggregases repressed in the absence of substrate and how does substrate binding trigger AAA+ protein activation? Our preliminary data point to various layers of ClpG and ClpL activity control, including the formation of alternative, large assembly states and ATPase control in hexameric rings. All layers are regulated by substrate binding and involve extra domains that are fused to the ATPase domains of ClpG and ClpL. We want to explore the pathways of substrate-triggered disaggregase activation and how the different layers are functionally intertwined.

Methods that will be used: Construction, purification and characterization of disaggregase mutants including size (using size-exclusion chromatography, dynamic light scattering and electron microscopy) and activity (using colorimetric and fluorescence-based assays) determination. Structural changes will be monitored by DSS crosslinking coupled to mass spectrometry (XL-MS). In vivo characterizations will include growth assays, fluorescence microscopy and bioluminescence measurements.

Key Responsibilities:

• Conduct cutting-edge research on AAA+ protein mechanism and activity control
• Utilize FRET-based assays to study the dynamics of AAA+ protein assemblies
• Construction, purification and biochemical characterization of AAA+ protein variants

Qualifications:

• A Master's degree or equivalent in Cell Biology, Molecular Biology, Biochemistry, or a related field
• Strong background in biochemistry
• Excellent communication skills and the ability to work independently

Why Join Us?

• Be part of a vibrant research community at ZMBH, one of the leading institutes for molecular biology
• Access state-of-the-art facilities and resources in Heidelberg, a city renowned for its scientific excellence

The PhD position is funded in the first instance for 3 years and is available from April 1, 2025. The remuneration is based on TV-L scale (E13, 65%).

Application deadline: April 30, 2025

Interested?

Please send applications (CV, motivation letter, 2-3 referees and a copy of Bachelor and Master transcripts to Axel Mogk ( a.mogk@zmbh.uni-heidelberg.de ).

Mailing address: PD Axel Mogk, ZMBH, Heidelberg University, Im Neuenheimer Feld 345, D-69120 Heidelberg, Germany.

Heidelberg University stands for equal opportunities and diversity. Qualified female candidates are especially invited to apply. Persons with severe disabilities will be given preference if they are equally qualified. Information on job advertisements and the collection of personal data is available at www.uni-heidelberg.de/en/job-market .