ZMBH - Open Positions

Scientific Job Openings

Postdoc and PhD student positions (dry/wet lab): De novo gene birth and human evolution

Center for Molecular Biology (ZMBH), Heidelberg University, Germany

Postdoc and PhD student positions (3 years with possible extensions) are available immediately in the evolutionary genomics group of Henrik Kaessmann. Applications will be reviewed until the positions are filled.

We are seeking highly qualified and enthusiastic applicants with a keen interest in evolutionary questions and a talent and passion for experimental molecular/cellular work and/or bioinformatics analyses (i.e., both joint and distinct dry/wet lab projects are possible).

Our lab has been interested in a range of topics related to the origins and evolution of organs in mammals and other vertebrates and the various underlying genomic changes (see “Selected Publications” below). In the framework of our research, we have generated and analyzed comprehensive genomics (e.g., RNA-seq, ATAC-seq) datasets based on samples from our large organ collections. More recently, we have begun to bring the work of our lab to the level of single cells using state-of-the-art single-cell genomics technologies and bioinformatics procedures. We have also started to experimentally assess the evolutionary impact of selected genomic changes.

The positions will be funded by a recently awarded grant from the NOMIS Foundation (https://nomisfoundation.ch/). In the framework of this grant, we seek to unravel the evolutionary impact of a particularly intriguing class of new genes: protein-coding genes that arose “from scratch” (i.e., from previously noncoding DNA sequence) during evolution – so-called de novo genes. Specifically, we will investigate the prevalence and functional roles of de novo genes in organ development across primates and thus shed light on the molecular evolution underlying the unique biology of humans, in particular that of the brain.

The work will rely on the generation and analyses of translatome (ribosome profiling) data across a unique set of prenatal developmental tissue samples, and the experimental characterization of selected de novo genes in state-of-the-art in vitro organoid systems, ex vivo fetal tissue cultures, and in vivo transgenic mouse models. Notably, the work will be carried out in the framework of collaborations with the labs of Barbara Treutlein (ETH, Basel), Gray Camp (Roche, Basel), and Svante Pääbo (MPI, Leipzig).

Experience in evolutionary and/or developmental biology and/or any of the aforementioned experimental techniques/models are a plus. The individual projects will be developed together with the candidates, based on their respective interests and dry/wet lab skills.

Note that people interested in other topics covered in our lab are also highly welcome to apply (funding is available for strong candidates).

In our lab, we attach great importance to a highly collaborative and positive team spirit! Indeed, we have various “mini-teams” of dry and wet lab researchers within the lab, who enthusiastically drive projects forward in remarkable ways. We are also particularly fond of the diverse cultural backgrounds of our lab members, which contribute to a very enriching atmosphere.

The language of our institute is English and its members form a highly international group. The ZMBH is located in Heidelberg, a picturesque international city next to the large Odenwald forest and Neckar river. The city offers a very stimulating, diverse and collaborative research environment, with the European Molecular Biology Laboratory (EMBL), German Cancer Research Center (DKFZ), Heidelberg Institute of Theoretical Studies (HITS), and the Max Planck Institute for Medical Research located in close proximity to the University.

For more information on the group and our institute more generally, please refer to our website at the ZMBH (http://www.zmbh.uni-heidelberg.de/Kaessmann/).

Please submit a CV, statement of research interest, and names of three references to: Henrik Kaessmann (h.kaessmann@zmbh.uni-heidelberg.de).

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Selected publications:

Murat, F., Mbengue, N., Boeg Winge, S., Trefzer, T., Leushkin, E., Sepp, M., Cardoso-Moreira, M., Schmidt, J., Schneider, C., Mößinger, K., Brüning, T., Lamanna, F., Riera Belles, M., Conrad, C., Kondova, I., Bontrop, R., Behr, R., Khaitovich, P., Pääbo, S., Marques-Bonet, T., Grützner, F., Almstrup, K., Heide Schierup, M., Kaessmann, H. (2022) The molecular evolution of spermatogenesis across mammals. Nature (in press)

Sarropoulos, I., Sepp, M., Fromel, R., Leiss, K., Trost, N., Leushkin, E., Okonechnikov, K., Joshi, P., Giere, P., Kutscher, L.M., Cardoso-Moreira, M., Pfister, S.M., and Kaessmann, H. (2021) Developmental and evolutionary dynamics of cis-regulatory elements in mouse cerebellar cells. Science 373: eabg4696.

Mazin, P.V., Khaitovich, P., Cardoso-Moreira, M., and Kaessmann, H. (2021) Alternative splicing during mammalian organ development. Nat. Genet. 53:924-935.

Wang, Z.Y., Leushkin, E., Liechti, A., Ovchinnikova, S., Mossinger, K., Bruning, T., Rummel, C., Grutzner, F., Cardoso-Moreira, M., Janich, P., Gatfield, D., Diagouraga, B., de Massy, B., Gill, M.E., Peters, A.H.F.M., Anders, S., and Kaessmann, H. (2020) Transcriptome and translatome co-evolution in mammals. Nature 588: 642-647.

Cardoso-Moreira M., Halbert, J., Valloton, D., Velten, B., Chen, C., Shao, Y., Liechti, A., Ascencao, K., Rummel, C., Ovchinnikova, S., Mazin, P.V., Xenarios, I., Harshman, K., Mort, M., Cooper, D.N., Sandi, C., Soares, M.J., Ferreira, P.G., Afonso, S., Carneiro, M., Turner, J.M., VandeBerg, J.L., Fallahshahroudi, A., Jensen, P., Behr, R., Lisgo, S., Lindsay, S., Khaitovich, P., Huber, W., Baker, J., Anders, S., Zhang, Y.E., and Kaessmann H. (2019) Gene expression across mammalian organ development. Nature 571: 505-509.

Sarropoulos, I., Marin, R., Cardoso-Moreira, M., and Kaessmann, H. (2019) Developmental dynamics of lncRNAs across mammalian organs and species. Nature 571: 510-514.

Cortez, D., Marin, R., Toledo-Flores, D., Froidevaux, L., Liechti, A., Waters, P.D., Grutzner, F., and Kaessmann, H. (2014) Origins and functional evolution of Y chromosomes across mammals. Nature 508: 488-493.

Necsulea, A., Soumillon, M., Warnefors, M., Liechti, A., Daish, T., Zeller, U., Baker, J.C., Grutzner, F., and Kaessmann, H. (2014) The evolution of lncRNA repertoires and expression patterns in tetrapods. Nature 505: 635-640.

Brawand, D., Soumillon, M., Necsulea, A., Julien, P., Csardi, G., Harrigan, P., Weier, M., Liechti, A., Aximu-Petri, A., Kircher, M., Albert, F.W., Zeller, U., Khaitovich, P., Grutzner, F., Bergmann, S., Nielsen, R., Paabo, S., and Kaessmann, H. (2011) The evolution of gene expression levels in mammalian organs. Nature 478: 343-348.

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).

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

Project Title: Structure-function analysis of J-domain cochaperones

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 chaperone machinery. Hsp70 chaperones are central hubs of the protein quality control network and work in collaboration with J-domain cochaperones and nucleotide exchange factors to facilitate a wide variety of protein folding processes and so (re)establish protein homeostasis. The Hsp70s are highly dynamic nanomachines that modulate the conformation of their substrate polypeptides by transiently binding to short, mostly hydrophobic stretches. This interaction is regulated by an intricate allosteric mechanism. The J-domain cochaperones target Hsp70 to their polypeptide substrates, and the nucleotide exchange factors regulate the lifetime of the Hsp70-substrate complexes. In vivo, Hsp70 and J-domain cochaperones are modified by posttranslational modifications and the aim of this PhD project will be to analyze the molecular mechanism J-domain proteins in vitro using biochemical and biophysical techniques with purified proteins. Complementary in-vivo-experiments will be carried out in E. coli and mammalian cell culture.

References:
Mayer, M.P. The Hsp70-chaperone machines in bacteria, Front Mol Biosci. (2021) Jun 7;8:694012. doi: 10.3389/fmolb.2021.694012
Mayer, M. P. & Gierasch, L. M. Recent advances in the structural and mechanistic aspects of Hsp70 molecular chaperones. Journal of Biological Chemistry jbc.REV118.002810 (2018). doi:10.1074/jbc.REV118.002810
Kityk, R., Kopp, J. & Mayer, M. P. Molecular Mechanism of J-Domain-Triggered ATP Hydrolysis by Hsp70 Chaperones. Molecular Cell 69, 227–237.e4 (2018).
Kityk, R., Vogel, M., Schlecht, R., Bukau, B. & Mayer, M. P. Pathways of allosteric regulation in Hsp70 chaperones. Nat Commun 6, 8308 (2015).
Mayer, M. P. Hsp70 chaperone dynamics and molecular mechanism. Trends in Biochemical Sciences 38, 507–514 (2013).

Methods that will be used:
Molecular biology methods, Protein purification methods, biochemical assays, fluorescence spectroscopy and mass spectrometry; E. coli 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 mammalian cell culture would be an advantage.

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

Non-Scientific Job Openings

Additional positions for research assistants and non-scientific personnel are also regularly published on the pages of the University's central job market:

Central job market of the University