University of Heidelberg

ZMBH - Open Positions


Scientific Job Openings

   
Listed 12.03.20  
 

PhD position:
Structural basis of AAA+ machines mediating protein disaggregation and degradation”
Center for Molecular Biology (ZMBH)
Heidelberg University
A sophisticated protein quality control system ensures protein homeostasis by degrading or refolding aberrant and aggregated proteins. The ring-forming AAA+ proteins are central components of this proteostasis network. They convert the chemical energy of ATP hydrolysis into a mechanical force to thread misfolded or aggregated proteins through their central channel. The fate of a threaded substrate protein will depend on the identity of the particular AAA+ protein. AAA+ proteins can associate with peptidases to form ATP-driven proteases, leading to substrate degradation. Other AAA+ proteins work independent of peptidases and direct substrates to refolding pathways.
We are studying the functions and mechanisms of AAA+ proteins from pathogenic bacteria. Their activities are crucial for stress resistance but can also play important roles in bacterial virulence. Accordingly, the AAA+ member ClpC was recently identified as antibacterial drug target. Our aim is to understand how AAA+ proteins work and how their threading activity is regulated. This activity control is crucial for cellular integrity as deregulation of AAA+ function by either mutations or small molecules is toxic to cells.
The project will focus on two AAA+ proteins: ClpC, which forms the core component of the central MecA/ClpC/ClpP protease, and ClpL, which acts as standalone disaggregase to confer superior heat resistance to bacteria. We want to determine the structural organization of ClpC and ClpL hexamers by cryo electron microscopy and how their structures are modulated upon partner, substrate or small molecule binding. Additionally we plan to determine the structure of the aggregate binding domain of ClpL by NMR spectroscopy. Determined structures will be validated by site-specific crosslinking experiments and designed mutants that will be characterized by a multiplicity of biochemical and cell biological methods.
The highly motivated PhD student should have a background in biochemistry or structural biology. Successful candidates will be part of an international team of PhD students and postdocs that works at the forefront of scientific research. The PhD student will be a member of the Heidelberg Biosciences International Graduate School (HBIGS) (http://www.hbigs.uni-heidelberg.de/). The PhD position is funded for 3 years
Please send applications (CV, motivation letter, two references, bachelor and master transcripts) to Axel Mogk (a.mogk@zmbh.uni-heidelberg.de).

Relevant publications:
Katikaridis P, Meins L, Kamal SM, Romling U, Mogk A (2019) ClpG Provides Increased Heat Resistance by Acting as Superior Disaggregase. Biomolecules 9

Maurer M, Linder D, Franke KB, Jager J, Taylor G, Gloge F, Gremer S, Le Breton L, Mayer MP, Weber-Ban E, Carroni M, Bukau B, Mogk A (2019) Toxic Activation of an AAA+ Protease by the Antibacterial Drug Cyclomarin A. Cell Chem Biol 26: 1169-1179 e4
Mogk A, Bukau B, Kampinga HH (2018) Cellular Handling of Protein Aggregates by Disaggregation Machines. Mol Cell 69: 214-226
Carroni M, Franke KB, Maurer M, Jager J, Hantke I, Gloge F, Linder D, Gremer S, Turgay K, Bukau B, Mogk A (2017) Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control. eLife 6

   
Listed 12.02.20  
   
 

A Research Scientist (m/f/d)

The Core Facility for Mass Spectrometry and Proteomics at the Center for Molecular Biology of Heidelberg University (ZMBH) has an opening for

A Research Scientist (m/f/d)

Fulltime position, starting date: immediately

The PhD scientist will initially be employed at the postdoc level, but with the possibility of a permanent and, if applicable, higher-graded position in future, provided all prerequisites are met. The scientist will collaborate with the different research groups of the ZMBH and other institutes of the Heidelberg Molecular Life Science Campus on diverse projects involving qualitative and quantitative proteomics. These projects require SILAC and other labeling techniques for quantitation, identification and localization of posttranslational modifications, including phosphorylation, acetylation and sumoylation. The successful candidate is expected to advise and support the research groups in setting up experiments, to manage data acquisition and analysis, and to discuss the results in-depth. Joint publications are possible. Acquisition of third-party funding is encouraged. The successful candidate will contribute to the development of the facility including acquisition of new methods and instruments.

The Core Facility for Mass spectrometry and Proteomics is equipped with a nano-LC QExactive, two nanoLC-Orbitrap MS systems and a nanoUPLC-QTRAP5500 system:

http://www.zmbh.uni-heidelberg.de/Central_Services/Mass_Spectrometry/default.html

Your ideal qualifications

  • Ph.D. in chemistry, pharmaceutics, biology or related fields
  • Expert knowledge in liquid chromatography mass spectrometry and MS/MS using CID and possibly ETD
  • Experience in various quantitative proteomics techniques, in particular SILAC, and/or detection and localization of posttranslational modifications
  • Proficiency in data analysis including database searches and software for quantitative proteomics
  • Hands-on experience in preparation of biological samples
  • Team working abilities, leadership qualities and aptitude in guiding technical assistants
  • Excellent written and spoken English language skills, German will be an advantage

The position is advertised for two years, initially. Payment will be according to German TV-L (full-time). A kindergarten service is available.

Contact: Dr. T. Ruppert (+49 6221 546895), Apl. Prof. Dr. M. Mayer (+49 6221 546829)

Application Deadline: March 25, 2020. Evaluation will begin two weeks after the opening date of the announcement.

Please submit your applications online to jmsr@zmbh.uni-heidelberg.de

The University of Heidelberg is an equal opportunity employer and encourages applications from qualified female candidates. Handicapped applicants will be given preference in the case of equal qualifications.

Information on the collection of personal data in accordance with Art. 13 DS-GVO can be found on our homepage at https://www.uni-heidelberg.de/universitaet/beschaeftigte/service/personal/datenschutz_personal.html

 

   
Listed 09.01.20  
 

PhD position:
“Microtubules – building them at the right time, at the right place”

Centre for Molecular Biology (ZMBH)
Heidelberg University

Microtubules are highly dynamic polymers with essential functions in chromosome segregation in mitosis and meiosis, intracellular organization, cell motility and neurogenesis. Microtubules are targets for drugs that are used in cancer therapy (Paclitaxel and Vinca alkaloids). Microtubule malfunction is associated with cancer, infertility and neurological diseases.

Using gamma-tubulin complexes, cells have developed mechanisms for the assembly of microtubules from tubulin subunits. We just have resolved the high resolution cryo-EM structure of the large vertebrate gamma-tubulin ring complex (gamma-TuRC) composed of over 30 subunits (published in Nature 2019). Unexpectedly, we identified actin as a component of the gamma-TuRC. The activity of the gamma-TuRC is modulated in time and space by accessory factors, for example microtubule polymerases and activators such as the microcephaly protein CDK5RAP2.

In this project we aim to understand the role of actin in the gamma-TuRC, when and where regulatory co-factors play a role, how they impact the structure of the gamma-TuRC and how the activity of these regulators is changed in cancer and adapted in specific cell types, for example neurons.

The PhD student will be using a broad range of techniques such as cryo-electron microscopy, CRISPR/Cas9 technology for genomic knock-ins and knockouts and live cell imaging to study microtubule assembly.
The highly motivated PhD student should have a background in biochemistry or cell biology. Successful candidates will be part of an international team of PhD students and postdocs that works at the forefront of scientific research. The PhD student will be a member of the Heidelberg Biosciences International Graduate School (HBIGS) (http://www.hbigs.uni-heidelberg.de/). The PhD position is funded for 3 years

Please send applications (CV, motivation letter, two references, bachelor and master transcripts) to E. Schiebel (schiebel.elmar@zmbh.uni-heidelberg.de).

Relevant publications:

Liu P, Zupa E, Neuner A, Böhler A, Loerke J, Flemming D, Ruppert T, Rudack T, Peter C, Spahn C, Gruss OJ, Pfeffer S, Schiebel E (2019). Insights into the assembly and activation of the microtubule nucleator γ-TuRC. Nature. doi: 10.1038/s41586-019-1896-6. 
Gunzelmann J, Ruthnick D, Lin TC, Zhang W, Neuner A, Jakle U, Schiebel E (2018) The microtubule polymerase Stu2 promotes oligomerization of the gamma-TuSC for cytoplasmic microtubule nucleation. Elife 7: e39932
Lin TC, Neuner A, Flemming D, Liu P, Chinen T, Jakle U, Arkowitz R, Schiebel E (2016) MOZART1 and gamma-tubulin complex receptors are both required to turn gamma-TuSC into an active microtubule nucleation template. J Cell Biol 215: 823-840
Lin TC, Neuner A, Schiebel E (2015) Targeting of gamma-tubulin complexes to microtubule organizing centers: conservation and divergence. Trends Cell Biol 25: 296-307
Lin TC, Neuner A, Schlosser YT, Scharf AN, Weber L, Schiebel E (2014) Cell-cycle dependent phosphorylation of yeast pericentrin regulates gamma-TuSC-mediated microtubule nucleation. Elife 3: e02208
Gombos L, Neuner A, Berynskyy M, Fava LL, Wade RC, Sachse C, Schiebel E (2013) GTP regulates the microtubule nucleation activity of gamma-tubulin. Nat Cell Biol 15: 1317-27
Erlemann S, Neuner A, Gombos L, Gibeaux R, Antony C, Schiebel E (2012) An extended γ-tubulin ring functions as a stable platform in microtubule nucleation. J Cell Biol 197: 59-74
Knop M, Schiebel E (1998) Receptors determine the cellular localization of a γ-tubulin complex and thereby the site of microtubule formation. EMBO J 17: 3952-3967

   
Listed 10.12.19  
 

The following position is available at the Faculty of Biosciences of Heidelberg University:

Tenure Track Professorship (W1 with Tenure Track to W3) on
CELLULAR BEHAVIOR IN NATURAL AND SYNTHETIC ENVIRONMENTS

 

Heidelberg University is an internationally highly recognized institution for fundamental research and teaching. Its Faculty of Biosciences, the Centre for Organismal Studies Heidelberg (COS) and the Center for Molecular Biology of Heidelberg University (ZMBH) are embedded in one of Germany's largest campuses for the life sciences. The recently founded cluster of excellence "3D Matter Made to Order" (3DMM2O), with research groups located at Heidelberg University and the Karlsruhe Institute of Technology, the COS and the ZMBH  jointly establish this new tenure track professorship. It will be based at the ZMBH and co-affiliated with the COS and the cluster of excellence.

The successful candidate will establish a cutting-edge research program addressing modern cell biology and engineering aspects. Fields of interest include – but are not limited to – topics such as

  • Imaging forces and mechanics in tissues
  • Cell behavior in organoids
  • Cellular decision making in complex environments
  • Engineering synthetic systems to control cell behavior

 

Applicants should use state-of-the-art approaches to analyze cell biology and complex cellular systems in natural and synthetic environments and have outstanding research and publication records corresponding to their career stage. Active participation within the cluster "3D Matter Made to Order" is required and participation in collaborative research centers as well as in teaching at Bachelor and Master student level are expected. The initial position includes 100% salary support and a research support budget commensurate with that for an assistant professorship.

We offer an excellent international research environment, which is complemented by additional academic institutes and research centers. There are numerous scientific core facilities in house and on campus. Examples are protein analytics including mass spectrometry, metabolomics, advanced light microscopy, electron microscopy, flow cytometry, RNAi screening, deep sequencing, and animal facilities.

More information on research and teaching programs can be found on our websites https://www.zmbh.uni-heidelberg.de/http://www.zmbh.uni-heidelberg.de and https://www.cos.uni-heidelberg.de/

The junior professorship position is a temporary qualification position for researchers with an excellent doctor's degree and proven teaching skills who are ready to start their independent research group and generally should not have spent more than three years as a postdoctoral researcher. The detailed conditions of employment are laid down in Article 51 of the Higher Education Law of the state of Baden-Württemberg. The evaluation statute can be downloaded from the homepage of the Human Resources Division (http://www.uni-heidelberg.de/tenuretrack).

Heidelberg University seeks to increase the number of female scientists in faculty positions and therefore strongly encourages applications by qualified women. Applicants with a handicap and equivalent qualifications will be given preference.

The application package should include a curriculum vitae, a list of publications, a list of current research support, a summary of teaching experience, a research summary, an outline of future research interests and a list of references including contact information.
Applications should be sent no later than 15.01.2020 by e-mail to Prof. Dr. E. Schiebel, Director of the ZMBH: direktor@zmbh.uni-heidelberg.de.

   
Listed 29.5.19  
 

Master Projects

in the laboratory of Prof. E. Schiebel, Centre for Molecular Biology (ZMBH), University of Heidelberg, Germany

My laboratory at the ZMBH, University of Heidelberg, is offering Master projects in the following areas:

The structure and function of gamma-tubulin complexes.  Gamma-tubulin complexes assemble microtubules from tubulin subunits. Microtubules have essential functions for chromosome segregation in mitosis and meiosis, fertility, transport process in particularly in neurons. Drugs such as Taxol that target tubulin are broadly used in cancer therapy. Gamma-tubulin complexes regulate the spatial and temporal formation of microtubules. In this project we determine the structure of gamma-tubulin complexes by Cryo-EM. We will also analyse how gamma-tubulin complexes interact with microtubule polymerases.

Centrosome duplication and centriole-centrosome conversion. Centrosomes are the main microtubule organizing centres in human cells. They only duplicate once per cell cycle. Misregulation of centrosome duplication triggers a p53 response and G1 arrest. This safeguard mechanism is bypassed in cancer cells. After duplication in S phase centrosomes convert into mature centrosomes. Here we analyse the molecular mechanism of this conversion process.

Centrosome cohesion. The two centrosomes of a cell are linked together into one unit from G1 until G2 phase. At the beginning of mitosis this linkage is resolved by the kinase NEK2. Here we will study molecular mechanisms of this linkage, the structure of the linker and functional consequences if centrosome cohesion fails.

Nuclear pore complex biogenesis and spindle pole body duplication. Nuclear pore complexes and the yeast spindle pole body (SPB; yeast microtubule organizing centre) are both embedded in the double membrane of the nuclear envelope. Here we aim to understand how large protein assemblies become inserted into the nuclear envelope and how the inner and outer nuclear envelopes fuse during this embedding process.

 

During the 6-month master project, you will receive a Student Assistant Contract (Hiwi contract).

 

Please send applications with a short motivation letter, CV, bachelor transcripts and the name of one referee to Prof. Dr. E. Schiebel (schiebel.elmar@zmbh.uni-heidelberg.de).

   
Listed 29.5.19  
 

Lab Rotation in the Laboratory of Prof. Elmar Schiebel, ZMBH, Heidelberg University

My laboratory at the ZMBH, Heidelberg University, is offering lab rotations (6-8 weeks) for Master students who are interested in cell biology, molecular biology or biochemistry.

Topics are:

The structure and function of gamma-tubulin complexes.  Gamma-tubulin complexes assemble microtubules from tubulin subunits. Microtubules have essential functions for chromosome segregation in mitosis and meiosis, fertility, transport process in particularly in neurons. Drugs such as Taxol that target tubulin are broadly used in cancer therapy. Gamma-tubulin complexes regulate the spatial and temporal formation of microtubules. In this project we determine the structure of gamma-tubulin complexes by Cryo-EM.

Genomic tagging of genes in human cells. Presently we are establishing and optimizing approaches based on gRNA and Cas9-like enzymes to tag human genes at the 3’ and 5’ end with a toolbox of PCR cassettes (NeonGreen, GFP, mRuby, auxin degron tag). This allows tagging of human genes within 20 days.

Centrosome duplication and centriole-centrosome conversion. Centrosomes are the main microtubule organizing centres in human cells. They only duplicate once per cell cycle. Misregulation of centrosome duplication triggers a p53 response and G1 arrest. This safeguard mechanism is bypassed in cancer cells. After duplication in S phase centrosomes convert into mature centrosome. Here we analyse the molecular mechanism of the conversion process.

Nuclear pore complex biogenesis and spindle pole body duplication. Nuclear pore complexes and the yeast spindle pole body (SPB; yeast microtubule organizing centre) are both embedded in the double membrane of the nuclear envelope. Here we aim to understand how large protein assemblies become inserted into the nuclear envelope and how the inner and outer nuclear envelopes fuse during this embedding process.

Please send applications to E. Schiebel:
schiebel.elmar@zmbh.uni-heidelberg.de

   
Listed 5.2.19  
 

Project Title: Interaction of Hsp90 with cochaperones and client proteins

Project leader: Matthias P. Mayer

Application Deadline: until position is filled

Start of PhD project: as soon as possible

Source of Funding: University of Heidelberg

Project Description:
In the center of this PhD project is the molecular mechanism of the Hsp70-Hsp90 chaperone machinery. Hsp70 and Hsp90 together with a large number of cochaperones form dynamic complexes with some 200 proteins in a native or near native state. Many of these “client” proteins are receptors, protein kinases and transcription factors involved in signal transduction and cell cycle regulation and depend on their interaction with Hsp70 and Hsp90 to become responsive to upstream signals. Thus, the Hsp70-Hsp90 chaperon machine is a key regulator of cell homeostasis, proliferation, differentiation, and programmed cell death and in recent years became a prime target for anti-tumor therapy. In this PhD project the fundamental questions are investigated of how the chaperone machine can interact with so many client proteins that are not related in sequence or structure and how this interaction regulates stability and activity of the clients. These questions will be addressed with biochemical and biophysical techniques using purified proteins. Complementary in-vivo-experiments will be carried out in yeast and mammalian cell culture.

References:
Graf C, Stankiewicz M, Kramer G, Mayer MP (2009) Spatially and kinetically resolved changes in the conformational dynamics of the Hsp90 chaperone machine. EMBO J 28: 602-613

Mayer MP & Le Breton L (2015) Hsp90: Breaking the Symmetry. Mol Cell 58: 8-20

Nguyen, M. T. N. et al. Isoform-Specific Phosphorylation in Human Hsp90β Affects Interaction with Clients and the Cochaperone Cdc37. Journal of Molecular Biology 429, 732–752 (2017).
Daturpalli, S., Knieß, R. A., Lee, C.-T. & Mayer, M. P. Large Rotation of the N-terminal Domain of Hsp90 Is Important for Interaction with Some but Not All Client Proteins. Journal of Molecular Biology 429, 1406–1423 (2017).

Methods that will be used:
Protein purification methods, biochemical assays, fluorescence spectroscopy and mass spectrometry; yeast genetics and mammalian cell culture.

Profile of candidate’s qualification:
The candidate should have a strong background in biochemistry/biophysics and should be highly motivated to succeed in science. Experience in yeast genetics or mammalian cell culture would be an advantage.

Please send this form to the HBIGS office by email to: r.lutz@hbigs.uni-heidelberg.de

 
 
 
 
   
 
 
 


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