Open Positions in the Mayer Lab

We are always interested in applications from highly motivated PhD students or Postdocs with a strong background in cellular and molecular biology and biochemistry. Please apply via e-mail with a motivation letter, CV and the contact details of references to m.mayer@zmbh.uni-heidelberg.de.

Project Description: 

The central theme of the here advertised position is to further our understanding of the molecular mechanism of the regulation of Hsf1, to lay the ground work for future developments of drugs that might activate or inhibit Hsf1 to ameliorate the treatment of diseases like cancer, Parkinson’s disease and ataxias. In previous studies in our lab we showed that Hsf1 is a thermosensor that reacts to the amount of heat absorbed from the environment by transiting from the monomeric to the trimeric state which is capable of binding to DNA and driving transcription. We could further show that Hsp70 chaperones regulate Hsf1 in a negative feedback loop by actively monomerizing the Hsf1 trimers and thereby dissociating them from DNA. However, there are still many questions open. The successful candidates will analyze the interaction of Hsf1 with molecular chaperones and cochaperones in vitro using purified proteins and biochemical and biophysical methods and with cell culture model systems. 

References: 

Hentze, N., Le Breton, L., Wiesner, J., Kempf, G. & Mayer, M.P. Molecular mechanism of thermosensory function of human heat shock transcription factor Hsf1. eLife 5:e11576 (2016); doi: 10.7554/eLife.11576 

Kmiecik, S.W., Le Breton, L. & Mayer, M.P. Feedback regulation of heat shock factor 1 (Hsf1) activity by Hsp70-mediated trimer unzipping and dissociation from DNA. The EMBO Journal 39:e104096 (2020); doi: 10.15252/embj.2019104096 

Kmiecik, S.W., Drzewicka, K., Melchior, F. & Mayer, M.P. Hsf1 is SUMOylated in the activated trimeric state. Journal of Biological Chemistry 296, 100324 (2021); doi: 10.1016/j.jbc.2021.100324 

Kmiecik, S.W. & Mayer, M.P. Molecular mechanism of heat shock factor 1 regulation, Trends in Biochemical Sciences, 47:218-232 (2022), doi: 10.1016/j.tibs.2021.10.004 

Methods that will be used: 

Protein purification, in vivo and in vitro protein-protein-interaction assays, fluorescence spectroscopy, hydrogen exchange mass spectrometry, protein-DNA interaction assays (EMSA, fluorescence polarization), fluorescence microscopy, life cell imaging, immunoprecipitation 

Profile of candidate’s qualification:

The candidate should be highly motivated to succeed in science, should hold a PhD in Biosciences, Biochemistry, or Biotechnology and should have ample experience in protein purification and biochemical assays. Previous work with cell culture and microscopy would be an asset. 

WebPage: https://www.zmbh.uni-heidelberg.de/Mayer/default.shtml 

E-Mail: m.mayer@zmbh.uni-heidelberg.de