Ruprecht-Karls-Universitšt Heidelberg






Open Positions

We are always considering unsolicited applications of outstanding and motivated candidates for PhD and postdoc positions.

The Bukau operates in a team-oriented manner. Although every PhD student and postdoc works on a distinct project, the projects typically are embedded in a collaborative framework within the lab, where help with daily issues is provided, and other lab members make contributions to a given project. We are an ambitious and internationally competitive lab, but we maintain a relaxed and friendly atmosphere where social interactions and fun are important.


PhD position

"Protein synthesis and cancer: Co-translational action of Hsp70 and Hsp90 chaperones in cancer cells "
Center for Molecular Biology (ZMBH), Heidelberg University

The classical Hsp90 function is to repeatedly bind and stabilize substrates proteins post-translationally.

Cancer cells abuse the cytoprotective function of molecular chaperones to support their proliferation, survival and malignant progression. Among the most relevant chaperones are the heat-shock proteins 70 and 90 which combat stress-induced protein misfolding, prevent the aggregation of misfolded proteins and support the folding of newly synthesized proteins. In particular Hsp90 has been described as a driver of the malignant phenotype, by keeping mutant oncoproteins in an active state.

Our recent findings challenge this view and suggest that Hsp90, often together with Hsp70, engages many substrates co-translationally. Aiming at a molecular understanding of this activity to cancer progression, the proposed project will explore the principles governing chaperone interactions with nascent chains during ongoing synthesis, determine how this function is highjacked and altered by cancer cells, and especially investigate the role of chaperones in folding of mutant oncogenes. Once established, we will explore whether these mechanisms can be therapeutic targets for cancer treatment. Methods employed include established biochemical and molecular biology tools, as well as the deep-sequencing based methods ribosome profiling (RP) and selective ribosome profiling (SeRP), which allows quantifying proteome-wide interactions of nascent polypeptides with chaperones..


Desired qualifications*:
We are looking for a highly motivated person who enjoys working in a team and has general knowledge of molecular biology, biochemistry and cancer biology. The successful candidate should have basic knowledge in bioinformatics and a strong interest in studying protein folding and quality control in health and disease.

Keywords*:
protein synthesis, translation, ribosome profiling, bioinformatics, protein misfolding and cancer.

Please send applications (CV, motivation letter, two references, bachelor and master transcripts) to Bernd Bukau (bukau@zmbh.uni-heidelberg.de) or Günter Kramer (g.kramer@zmbh.uni-heidelberg.de).

Relevant publications:

i. Original references:

Döring, K., Ahmed, N., Riemer, T., Suresh, H.G., Vainshtein, Y., Habich, M., Riemer, J., Mayer, M.P., O'Brien, E.P., Kramer, G., Bukau, B. Profiling Ssb-nascent chain interactions reveals principles of Hsp70-assisted folding. (2017) Cell 170:298-311.e20. doi: 10.1016/j.cell.2017.06.038. (Abstract).

Shiber, A., Döring, K., Friedrich, U., Klann, K., Merker, D., Zedan, M., Tippmann, F., Kramer, G., Bukau, B. (2018) Co-translational assembly of protein complexes in eukaryotes revealed by ribosome profiling. Nature, doi: 10.1038/s41586-018-0462-y (Abstract).

Bertolini, M., Fenzl, K., Kats, I., Wruck, F., Tippmann, F., Schmitt, J., Auburger, J.J., Tans, S., Bukau, B. and Kramer, G. Interactions between nascent proteins translated by adjacent ribosomes drive homomer assembly. Science (in press).

ii. Review:

Kramer, G., Shiber, A., Bukau, B. Mechanisms of Co-Translational Maturation of Newly Synthesized Proteins. (2019) Ann. Rev. Biochem., doi: 10.1146/annurev-biochem-013118-111717 (Abstract).





Carmen showing Josef a specimen through the microscope