We are looking for a motivated, enthusiastic PhD candidate (biology, biotechnology, biochemistry, chemistry, biomedical engineering or related disciplines) for a PhD thesis at the Institute of Biochemistry and Molecular Cell Biology on amphipathic helices in nuclear pore complexes.
Nuclear pore complexes (NPCs) are the gates of the nuclear envelope that mediate the selective transport of proteins and RNA between the inside of the cell nucleus and the cytoplasm. For this purpose, they deform the two membranes of the nuclear envelope into a pore. Amphipathic helices in a variety of nuclear pore proteins are crucial for this process. This DFG-funded project investigates how a newly identified amphipathic helix in the nuclear pore transmembrane protein NDC1 contributes to this process. Cell-free and cell-based assays will be used to test whether this motif is required for the assembly and function of NPCs in vertebrates. In minimal membrane systems (liposomes, giant unilamellar vesicles) the membrane binding of the helix, e.g., the preference for certain lipids, will be characterised and tested whether the helix can bend membranes by dipping into the lipid layer. As NDC1 interacts with other nuclear pore proteins that also possess amphipathic helices, the potential synergistic function of these helices for membrane curvature and the assembly and function of the NPC in minimal membrane systems and cellular assays will be analysed.
Your profile:
- Completed university education in biology / biotechnology / human biology / molecular medicine / biochemistry with an above-average Master's degree
- Strong interest in basic biochemical and cell biological research
- Basic knowledge of protein purification, cell culture, cell biology and molecular biology is helpful.
- Team-orientated work, enthusiasm for establishing new experimental models and above-average commitment is expected.
Selected literature:
Amm I, Weberruss M, Hellwig A, Schwarz J, Tatarek-Nossol M, Lüchtenborg C, Kallas M, Brügger B, Hurt E, Antonin W (2023). Distinct domains in Ndc1 mediate its interaction with the Nup84 complex and the nuclear membrane. Journal of Cell Biology 222(6):e202210059. doi: 10.1083/jcb.202210059
Kutay U, Jühlen R, Antonin W. (2021). Mitotic disassembly and reassembly of nuclear pore complexes. Trends in Cell Biology S0962-8924(21)00139-2. doi: 10.1016/j.tcb.2021.06.011
Hamed M & Antonin W. (2021). Dunking into the Lipid Bilayer: How Direct Membrane Binding of Nucleoporins Can Contribute to Nuclear Pore Complex Structure and Assembly. Cells. 10(12):3601. doi: 10.3390/cells10123601.
Contact:
Univ.-Prof. Dr. Wolfram Antonin
wantoninukaachende
Institut für Biochemie und Molekulare Zellbiologie
Medizinische Fakultät, RWTH Aachen
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 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.
If you are interested in the project, please apply with a short CV and a current overview of your grades from your degree programme.
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.
If you are interested in the project, please apply with a short CV and a current overview of your grades from your degree programme.
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 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.
If you are interested in the project, please apply with a short CV and a current overview of your grades from your degree programme.
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.
If you are interested in the project, please apply with a short CV and a current overview of your grades from your degree programme.
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
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 mitotic defects in hematopoietic malignancies at the Institute of Biochemistry and Molecular Cell Biology. The topic can be also addressed as research project for a medical thesis.
Myeloid malignancies are a set of diverse genetic and epigenetic disorders that affect hematopoietic stem and progenitor cells (HSPCs). Cells show reduced differentiation, faulty self-renewal, and hyperproliferation. These malignancies include myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN), which can secondarily develop into acute myeloid leukaemia (AML) by molecular mechanisms poorly defined to date but dependent on genetic instability. Also the reasons for the poor prognosis in hematopoietic malignancies is still ill-defined. Especially, the study of these diseases has traditionally neglected the detailed investigation of the cell division process. Here we will functionally characterize the impact in mitosis of important gene mutations typical for MPN and AML like those in the genes.
Important methods: Western blot, handling of cell tissue culture cells and patient samples, immunofluorescence, live-cell staining, confocal microscopy, life-cell imaging.
If you are interested in the project, please apply with a short CV and a current overview of your grades from your degree programme.
Selected publications:
Murati, A. et al. (2012) Myeloid malignancies: mutations, models and management. BMC Cancer. doi:10.1186/1471-2407-12-304.
Kitamura, T. et al. (2014) The molecular basis of myeloid malignancies. Proc Jpn Acad Ser B Phys Biol Sci. DOI: 10.2183/pjab.90.389
Grinfeld, J. et al. (2018) Classification and Personalized Prognosis in Myeloproliferative Neoplasms. N Engl J. doi:10.1056/NEJMoa1716614.
Papaemmanuil et al. (2016) Genomic Classification in Acute Myeloid Leukemia. N Engl J Med. doi:10.1056/NEJMc1608739.
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 an interdisciplinary bachelor or master thesis project on lipid extraction and analysis of the nuclear envelope at the Institute of Biochemistry and Molecular Cell Biology and the Institute for Molecular Cardiovascular Research. The topic can be also addressed as research project for a medical thesis.
The nuclear envelope is a subcompartment of the endoplasmic reticulum (ER) with very diverse and specific functions: It separates the interior of the nucleus from the remaining of the cell, interacts with chromatin and thereby influences gene expression, and is involved in cellular signal transduction processes. Whether and how lipids of the nuclear envelope influence these processes and the dynamic of the nuclear envelope is largely unclear. In this project, we will investigate whether the lipid composition of the nuclear envelope differs from the rest of the ER. For this purpose, membranes of the nuclear envelope and the rest of the ER will be isolated, different methods of lipid extraction from the membranes will be tested and optimized, and the lipid classes of the different membranes will be determined by LC-MS analysis.
Important methods: Handling of tissue culture cells and preparation of cell extracts, cell fractionation and immunoprecipitation for membrane isolation, lipid extraction, LC-MS analysis of lipids.
If you are interested in the project, please apply with a short CV and a current overview of your grades from your degree programme.
Selected publications:
De Magistris P, Antonin W (2018). The Dynamic Nature of the Nuclear Envelope. Curr Biol. 28(8):R487-R497. doi: 10.1016/j.cub.2018.01.073
Peeters BWA, Piët ACA, Fornerod M (2022). Generating Membrane Curvature at the Nuclear Pore: A Lipid Point of View. Cells 11(3):469. doi: 10.3390/cells11030469.
Noels H, Lehrke M, Vanholder R, Jankowski J (2021). Lipoproteins and fatty acids in chronic kidney disease: molecular and metabolic alterations. Nat Rev Nephrol. 17(8):528-542. doi: 10.1038/s41581-021-00423-5.
Schunk SJ, Hermann J, Sarakpi T, Triem S, Lellig M, Hahm E, Zewinger S, Schmit D, Becker E, Möllmann J, Lehrke M, Kramann R, Boor P, Lipp P, Laufs U, März W, Reiser J, Jankowski J, Fliser D, Speer T, Jankowski V. (2021). Guanidinylated Apolipoprotein C3 (ApoC3) Associates with Kidney and Vascular Injury. J Am Soc Nephrol. 32(12):3146-60. doi: 10.1681/ASN.2021040503.
Jankowski V, Saritas T, Kjolby M, Hermann J, Speer T, Himmelsbach A, Mahr K, Heuschkel MA, Schunk SJ, Thirup S, Winther S, Bottcher M, Nyegard M, Nykjaer A, Kramann R, Kaesler N, Jankowski J, Floege J, Marx N, Goettsch C (2022). Carbamylated sortilin associates with cardiovascular calcification in patients with chronic kidney disease. Kidney Int. 101(3):574-584. doi: 10.1016/j.kint.2021.10.018.
Zewinger S, Reiser J, Jankowski V, Alansary D, Hahm E, Triem S, Klug M, Schunk SJ, Schmit D, Kramann R, Körbel C, Ampofo E, Laschke MW, Selejan SR, Paschen A, Herter T, Schuster S, Silbernagel G, Sester M, Sester U, Aßmann G, Bals R, Kostner G, Jahnen-Dechent W, Menger MD, Rohrer L, März W, Böhm M, Jankowski J, Kopf M, Latz E, Niemeyer BA, Fliser D, Laufs U, Speer T (2020). Apolipoprotein C3 induces inflammation and organ damage by alternative inflammasome activation. Nat Immunol. 21(1):30-41. doi: 10.1038/s41590-019-0548-1
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 the link between the nucleoporin Nup50 and Amyotrophic Lateral Sclerosis (ALS) at the Institute of Biochemistry and Molecular Cell Biology. The topic can be also addressed as research project for a medical thesis.
Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease of which the causes remain to be fully understood. ALS induces a progressive paralysis of the patients’ muscles leading to their death. In a genetic screen, the nucleoporin Nup50 has been found to be associated with an increased risk of ALS. Together with other nucleoporins, Nup50 is part of the nuclear pores complex (NPC), a protein complex which mediates and controls macromolecule trafficking across the nuclear envelope. Different Nup50 domains, responsible for its interaction with Importin α, Importin β, RCC1, other nucleoporin or Ran are well identified and uphold Nup50 involvement in nuclear trafficking as well as NPC assembly. However, Nup50’s role in ALS remains elusive. Nup50 mutations associated with ALS have been identified throughout all Nup50 domains. This project aims to evaluate how these mutations impact Nup50 interaction with its identified partners and its underlying cellular functions, like nuclear transport or GTP homeostasis.
Important methods: protein interaction and GDP/GTP exchange assays, cell culture, immunofluorescence, fluorescence microscopy.
Selected publications:
Megat S, Mora N, Sanogo J, et al. (2023) Integrative genetic analysis illuminates ALS heritability and identifies risk genes. Nature communications 14(1):342.
Holzer G and Wolfram A. (2022) Nup50 plays more than one instrument., Cell cycle, 13;1-10
Holzer G, De Magistris P, Gramminger C, Sachdev R, Magalska A, Schooley A, Scheufen A, Lennartz B, Tatarek-Nossol M, Lue H, Linder M I, Kutay U, Preisinger C, Moreno-Andres D and Antonin W. (2021) The nucleoporin Nup50 activates the Ran guanine nucleotide exchange factor RCC1 to promote NPC assembly at the end of mitosis.EMBO Journal, 40:e108788
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 nuclear pore complexes in maintaining cellular compartmentalisation at the Institute of Biochemistry and Molecular Cell Biology. The topic can be also addressed as research project for a medical thesis.
The nuclear pore complex (NPC) is one of the largest protein complexes in cells that regulates effective transport across the nuclear envelope. It is composed by 30 subunits known as nucleoporins. NPC barrier is required to segregate nuclear and cytoplasmic compartments. Loss of certain nucleoporins results in loss of compartmentalisation and hence disruption of cellular functions. In this project we study the effect on cellular compartmentalization if specific nucleoporins are downregulated. To achieve this, we develop a protein reporter-based model to simulate nucleoporins loss during aging in cell culture. You will stably express a set of protein markers in cells and simulate the nucleoporin loss using auxin-mediated degradation of a specific nucleoporin. Live cell imaging will be used to track changes in the localization of different protein reporters. By the end of this project, you should be able to handle cells in cell culture, cell culture techniques and have an overview of cell imaging.
If you are interested in the project, please apply with a short CV and a current overview of your grades from your degree programme.
Selected publications:
De Magistris P, Suluyayla R, and Antonin W. (2018). Wie die Zelle ihre Kernporen aufbaut. BIOspektrum 24: 20–22.
Weberruss M and Antonin W (2016). Perforating the nuclear boundary - how nuclear pore complexes assemble. Journal of Cell Science 129 (24): 4439-4447.
Braun DA, Sadowski CE, Kohl S, Lovric S, Astrinidis SA, Pabst WL, Gee HY, Ashraf S, Lawson JA, Shril S, Airik M, Tan W, Schapiro D, Rao J, Choi WI, Hermle T, Kemper MJ, Pohl M, Ozaltin F, Konrad M, Bogdanovic R, Büscher R, Helmchen U, Serdaroglu E, Lifton RP, Antonin W, Hildebrandt F (2016). Mutations in nuclear pore genes NUP93, NUP205 and XPO5 cause steroid-resistant nephrotic syndrome. Nature Genetics, 48 (4): 457-465.
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 chromatin decondensation at the end of mitosis at the Institute of Biochemistry and Molecular Cell Biology. The topic can be also addressed as research project for a medical thesis.
Mitosis is the most impressive stage of the cell cycle. During mitosis the chromatin structure changes dynamically: at the beginning of mitosis chromatin condenses into densely-packed structures to enable correct segregation of the genetic material; at the end of mitosis chromatin decondenses to re-establish the interphase chromatin structure, making it accessible for DNA replication and transcription. To understand the molecular mechanisms involved in chromatin decondensation at the end of mitosis, we use live-cell imaging of human cells. We develop techniques to generate and analyse low- and high-throughput imaging data, and draw hypotheses from these how specific chromatin decondensation factors are involved in this process.
Some research questions you could address in your project include:
- How is RNA as an architectural molecule on the periphery of mitotic chromosomes involved in chromatin decondensation?
- How can distinct RNA helicases by acting on the periphery of mitotic chromosomes influence the decondensation of chromatin?
You will use the following methods in the lab:
Cell culture, siRNA and DNA transfection, high resolution live cell imaging, western blot
If you are interested in the project, please apply with a short CV and a current overview of your grades from your degree programme.
Selected publications:
Magalska A, Schellhaus AK, Moreno-Andrés D, Zanini F, Schooley A, Sachdev R, Schwarz H, Madlung J, Antonin W (2014). RuvB-like ATPases Function in Chromatin Decondensation at the End of Mitosis. Dev Cell 31, 305–318.
Antonin W and Neumann H (2016). Chromosome condensation and decondensation during mitosis. Curr Opin Cell Biol 40, 15–22.
Moreno-Andrés D, Yokoyama H, Scheufen A, Holzer G, Lue H, Schellhaus AK, Weberruss M, Takagi M, Antonin W (2020). VPS72/YL1-Mediated H2A.Z Deposition Is Required for Nuclear Reassembly after Mitosis. Cells 9, E1702.
Moreno-Andrés D, Bhattacharyya A, Scheufen A, Stegmaier J (2022). LiveCellMiner: A new tool to analyze mitotic progression. PLoS One 17, e0270923.
Contact:
Univ.-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 “Role of nucleoporin 88 in fetal akinesia” at the Institute of Biochemistry and Molecular Cell Biology. The topic can be also addressed as research project for a medical thesis.
Fetal akinesia deformation sequence (FADS) is a lethal neuromuscular disorder caused by defective proteins of the neuromuscular junction. Affected fetuses present with an inability to move in uterus. Fetal movement is prerequisite for proper embryonic development, and as a result, FADS fetuses suffer from various symptoms including joint contractures and lung hypoplasia. FADS fetuses are in many cases premature and stillborn; live-births do not survive due to their inability to breath. We found that mutations in the gene coding for nucleoporin 88 (NUP88) also lead to lethal FADS. NUP88 is a protein of the nuclear pore complex, a big macro-molecular structure in the nuclear envelope orchestrating transport between the nucleus and the cytoplasm.
In this project you will work on uncovering the molecular mechanisms leading to NUP88-related FADS. In the lab we work with primary tissue culture samples from FADS fetuses and we also use other human cells to model the disease using siRNA transfection. Given the neuromuscular phenotype in FADS we analyse the actin cytoskeleton in the cells which can serves as a mechanical model for muscle filaments. We use fluorescence microscopy and live-cell imaging for our analyses.
If you are interested in the project, please apply with a short CV and a current overview of your grades from your degree programme.
Selected publications:
Bonnin E, Cabochette P, Filosa A, Jühlen R, Komatsuzaki S, Hezwani M, Dickmanns A, Martinelli V, Vermeersch M, Supply L, Martins N, Pirenne L, et al. 2018. Biallelic mutations in nucleoporin NUP88 cause lethal fetal akinesia deformation sequence. PLoS Genet 14:e1007845.
Jühlen R and Fahrenkrog B. 2018. Moonlighting nuclear pore proteins: tissue-specific nucleoporin function in health and disease. Histochem Cell Biol 150:593–605.
Jühlen R, Martinelli V, Vinci C, Breckpot J, Fahrenkrog B. 2020. Centrosome and ciliary abnormalities in fetal akinesia deformation sequence human fibroblasts. Sci Rep 10:19301.
Jühlen R, Martinelli V, Rencurel C, Fahrenkrog B. 2023. Alteration of actin cytoskeletal organisation in fetal akinesia deformation sequence. bioRxiv 2023.06.12.544620; doi: doi.org/10.1101/2023.06.12.544620.
Contact:
Dr. Ramona Jühlen
rjuehlenukaachende
Institute of Biochemistry and Molecular Cell Biology
Medical Faculty, RWTH Aachen University
Pauwelsstrasse 30
52074 Aachen
