Open positions

We are looking for enthusiastic and motivated students (Biology, Biotechnology, Biochemistry, Chemistry, Biomedical Engineering or related disciplines) interested in a bachelor or master thesis project on GTPase activity of DRG1 at the Institute of Biochemistry and Molecular Cell Biology. The topic can be also addressed as research project for a medical thesis.

Small GTPases, also known as small GTP-binding proteins, act as molecular switches in many signal transduction pathways: GTP binding activates them, GTP hydrolysis sets them back in their inactive state. Well known members of this proteins family are ras, rho, rab or ran. In all these proteins the GTPase activity is stimulated by GAPs (GTPase activating proteins) and the GDP to GTP exchange by GEFs (guanine nucleotide exchange factors). However, a number of GTPases does not require these auxiliary factors, and in general these GTPase are much less studied. One of these GTPase, DRG1 (developmental regulated GTPase 1) will be analyzed in this project, especially its GTPAse activity: How is DRG1 activity affected by the different domains of the protein and by its different interaction partners? The results will contribute to our understand of how DRG1 acts in cells e.g. in the regulation of microtubule dynamics and cell division.

Important methods: bacterial protein expression and purification, biochemical GTP binding studies, enzymatic GTPase activity assays, protein interaction assays.

 

Selected publications:

Schellhaus AK, Moreno-Andrés D, Chugh M, Yokoyama H, Moschopoulou A, De S, Bono F, Hipp K, Schäffer E, Antonin W (2017). Developmentally Regulated GTP binding protein 1 (DRG1) controls microtubule dynamics. Scientific Reports. 7(1): 9996. doi: 10.1038/s41598-017-10088-5.

Lu L, Lv Y, Dong J, Hu S, Peng R (2016). DRG1 is a potential oncogene in lung adenocarcinoma and promotes tumor progression via spindle checkpoint signaling regulation. Oncotarget. 7:72795-72806. doi: 10.18632/oncotarget.11973.

Schellhaus, AK, De Magistris, P, and Antonin, W (2015). Nuclear reformation at the end of mitosis. Journal of Molecular Biology, 428 (10): 1962-85

 

Contact:

Prof. Dr. Wolfram Antonin
wantoninukaachende
Institute of Biochemistry and Molecular Cell Biology
Medical Faculty, RWTH Aachen University
Pauwelsstrasse 30
52074 Aachen

We are looking for enthusiastic and motivated students (Biology, Biotechnology, Biochemistry, Chemistry, Biomedical Engineering or related disciplines) interested in a bachelor or master thesis project on membrane binding of nuclear pore complex proteins at the Institute of Biochemistry and Molecular Cell Biology. The topic can be also addressed as research project for a medical thesis.

Nuclear pore complexes mediate the highly efficient and regulated transport across the nuclear envelope. They are formed by thirty different proteins, nucleoporins, which fuse the two membrane of the nuclear envelope to large pores and stabilize these (see also our research interests). Although anchored in the two membrane structure of the nuclear envelope most nucleoporins do not contain transmembrane regions. However, some of them directly interact with the nuclear membranes, which is crucial for different aspects of nuclear pore complex assembly and function. In this project we will characterize membrane binding sites in different nucleoporins using biochemical and microscopic membrane binding assays. Using very large liposomes, so called giant unilamellar vesicles (GUVs), which can be observed by fluorescence microcopy, the sequential and interdependent membrane interaction of nucleoporins will be studied and reconstituted in the context of nuclear pore complex assembly.

Important methods: bacterial protein expression and purification, labeling of recombinant proteins with fluorescent dyes, formation of small liposomes and giant unilamellar vesicles, (GUVs), fluorescence microscopy including confocal microscopy, liposome floatation assays.

 

Selected publications:

Vollmer B, Lorenz M, Moreno-Andres D, Bodenhöfer M, De Magistris P, Astrinidis SA, Schooley A, Flötenmeyer M, Leptihn S, and Antonin W (2015). Nup153 recruits the Nup107-160 complex to the inner nuclear membrane for interphasic nuclear pore complex assembly. Developmental Cell, 33 (6): 717-728.

Vollmer, B, Schooley, A, Sachdev, R, Eisenhardt, N, Schneider, AM, Sieverding, C, Madlung, J, Gerken, J, Macek, B, and Antonin, W (2012). Dimerization and direct membrane interaction of Nup53 contribute to nuclear pore complex assembly. EMBO Journal, 31 (20):4072-84.

von Appen A, Kosinski J, Sparks L, Ori A, DiGuilio AL, Vollmer B, Mackmull MT, Banterle N, Parca L, Kastritis P, Buczak K, Mosalaganti S, Hagen W, Andres-Pons A, Lemke EA, Bork P, Antonin W, Glavy JS, Bui KH, and Beck M (2015).In situ structural analysis of the human nuclear pore complex. Nature, 526 (7571): 140-143.

Holzer G and Antonin W (2018). Nuclear pore complexes: Global Conservation and Local Variation. Current Biology 28: R674–R677

 

Contact:

Prof. Dr. Wolfram Antonin
wantoninukaachende
Institute of Biochemistry and Molecular Cell Biology
Medical Faculty, RWTH Aachen University
Pauwelsstrasse 30
52074 Aachen

We are looking for enthusiastic and motivated students (Biology, Biotechnology, Biochemistry, Chemistry, Biomedical Engineering or related disciplines) interested in a bachelor or master thesis project on nucleophosmin dysfunction in acute myelogenous leukemia at the Institute of Biochemistry and Molecular Cell Biology. The topic can be also addressed as research project for a medical thesis.

Nucleophosmin, also known as NPM1, is a nuclear protein, which is often mutated in acute myelogenous leukemia and results in characteristic nuclear shape abnormalities, a so called cup structure. To gain insight into the nucleophosmin dysfunction in acute myelogenous leukemia and to understand how the nucleophosmin mutation affect nuclear structure we will compare biophysical and biochemical properties of wild type and the mutant nucleophosmin protein. The cellular localization and dynamics of both wild type and the mutant nucleophosmin will be studied in tissue culture cells including patient cell lines.

Important methods: bacterial protein expression and purification, handling of tissue culture cells, immunofluorescence, fluorescence microscopy including confocal microscopy, life cell imaging.

 

Selected publications:

Jost E, Herwartz R, Hoß M, Vankann L, Fuchs R. (2015). Cup-like blasts in acute myeloid leukemia. Am J Hematol. 90:847-8. doi: 10.1002/ajh.23954.

Grisendi S, Mecucci C, Falini B, Pandolfi PP (2006). Nucleophosmin and cancer. Nat Rev Cancer. 6:493-505.

Brunetti L, Gundry MC, Goodell MA. (2019). New insights into the biology of acute myeloid leukemia with mutated NPM1. Int J Hematol. doi: 10.1007/s12185-018-02578-7.

 

Contact:

Prof. Dr. Wolfram Antonin
wantonin@ukaachen.de

Institute of Biochemistry and Molecular Cell Biology,
Medical Faculty, RWTH Aachen University,
Pauwelsstrasse 30,
52074 Aachen

We are looking for enthusiastic and motivated students (Biology, Biotechnology, Biochemistry, Chemistry, Biomedical Engineering or related disciplines) interested in a bachelor or master thesis project on transmembrane proteins of nuclear pore complexes at the Institute of Biochemistry and Molecular Cell Biology. The topic can be also addressed as research project for a medical thesis.

Nuclear pore complexes mediate the highly efficient and regulated transport across the nuclear envelope. They are formed by thirty different proteins, nucleoporins, which fuse the two membrane of the nuclear envelope to large pores and stabilize these (see also our research interests). Many nucleoporins have been structurally analyzed, mostly by X-ray crystallography, in the last years, which is the basis for getting a high resolution structural picture of the entire nuclear pore complex. However, we lack structural information of the three transmembrane nucleoporins, in vertebrates POM121, NDC1 and GP210, despite the fact that these have essential functions within the nuclear pore complex as well as for its assembly and disassembly. In this project we will express and purify the three transmembrane nucleoporins and reconstitute them into nanodiscs, small membrane fragments which can be analyzed by different biophysical and biochemical techniques. This will provide insights into the transmembrane nucleoporins functions within nuclear pore complexes.

Important methods: bacterial protein expression and purification, labeling of recombinant proteins with fluorescent dyes, reconstitution of membrane proteins into nanodiscs, biochemical interaction studies.

 

Selected publications:

Mansfeld, J, Güttinger, S, Hawryluk-Gara, LA, Pante, N, Mall, M, Galy, V, Mühlhäusser, P, Wozniak, RW, Mattaj, IW, Kutay, U, and Antonin, W (2006). The conserved transmembrane nucleoporin NDC1 is required for nuclear pore complex assembly in vertebrate cells. Molecular Cell, 22:93-103

Silva Alves N, Astrinidis SA, Eisenhardt N, Sieverding C, Redolfi J, Lorenz M, Weberruss M, Moreno-Andrés D, Antonin W (2017). MISTIC-fusion proteins as antigens for high quality membrane protein antibodies. Scientific Reports 7:41519 | DOI: 10.1038/srep41519

von Appen A, Kosinski J, Sparks L, Ori A, DiGuilio AL, Vollmer B, Mackmull MT, Banterle N, Parca L, Kastritis P, Buczak K, Mosalaganti S, Hagen W, Andres-Pons A, Lemke EA, Bork P, Antonin W, Glavy JS, Bui KH, and Beck M (2015).In situ structural analysis of the human nuclear pore complex. Nature, 526 (7571): 140-143.

Holzer G and Antonin W (2018). Nuclear pore complexes: Global Conservation and Local Variation. Current Biology 28: R674–R677

 

Contact:

Prof. Dr. Wolfram Antonin
wantoninukaachende
Institute of Biochemistry and Molecular Cell Biology
Medical Faculty, RWTH Aachen University
Pauwelsstrasse 30
52074 Aachen

We are looking for motivated, enthusiastic students (biology, biotechnology, biochemistry, chemistry, biomedical engineering or related disciplines) who would like to do their bachelor or master thesis at the Institute of Biochemistry and Molecular Cell Biology on life cell imaging of nuclear reformation at the end of mitosis. The topic is also suitable as a doctoral project for students of medicine / dentistry.

During mitosis in animal cells, the nucleus undergoes extensive structural and functional changes (see also our research interests). At the beginning of mitosis, the nuclear membrane breaks down. Then, the chromatin is condensed in single rod-shaped chromosomes, which are captured and separated by the mitotic spindle. The molecular mechanisms that occur in these early mitotic phases have been extensively studied. However, much less is known about how the nucleus is reconstructed at the end of mitosis to form a fully functional interphase nucleus. Using RNAi mediated downregulation of target genes combined with life cell imaging we have identified several factors with potential crucial functions in nuclear assembly. Within this project, we will characterize these factors in detail using life cell imaging of cell lines with different fluorescent nuclear envelope, chromatin and spindle markers as well as immunofluorescence of nuclear structures.

Important methods: handling of cell culture cells, cell transfections, immunofluorescence, microscopy including confocal microscopy, life-cell imaging, siRNA technology, biochemical binding assays.

 

Selected publications:

Yokoyama H, Moreno-Andres D, Astrinidis SA, Hao Y, Weberruss M, Schellhaus AK, Lue H, Haramoto Y, Gruss OJ, Antonin W. (2019). Chromosome alignment maintenance requires the MAP RECQL4, mutated in the Rothmund-Thomson syndrome. Life Science Alliance 2(1). pii: e201800120. doi: 10.26508/lsa.201800120.

Schooley A, Moreno-Andrés D, De Magistris P, Vollmer B, and Antonin W (2015). The lysine demethylase LSD1 is required for nuclear envelope formation at the end of mitosis. Journal of Cell Science, 128 (18): 3466-3477.

 

Contact:

Prof. Dr. Wolfram Antonin
wantoninukaachende
Institute of Biochemistry and Molecular Cell Biology
Medical Faculty, RWTH Aachen University
Pauwelsstrasse 30
52074 Aachen