Dr. rer. nat. Ramona Jühlen
Location: Etage 6, Gang D, Raum 13
Tel.: 0241 80-88414
rjuehlenukaachende
PhD students:
Sabine Wiesmann, M.Sc.
Tel.: 0241 80-88414
sabwiesmannukaachende
Bachelor and Master students:
Isabel Braun, Master student
Jana Meißner, Bachelor student
Alumni:
Chantal Strobel, Bachelor student FH Aachen (03/2021-07/2021)
Carmen Llera-Brandt, Bachelor student FH Aachen (08/2023-01/2024)
Lukas Grauer, Master student RWTH Aachen (06/2023-04/2024)
Chromatin decondensation during mitotic exit
Our body’s tissue and organs constantly need to produce new cells in a process termed cell cycle. The cell cycle consists of two main stages: interphase and mitosis. During interphase the cell grows and DNA is replicated and transcribed. During mitosis the genetic material of a parent cell is divided into two new daughter cells.
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.
On the one hand, molecular mechanisms regulating chromatin condensation are well-studied. On the other hand, chromatin decondensation is a cellular process with still many open questions.
To understand the molecular mechanisms involved in chromatin decondensation at the end of mitosis, we use live-cell imaging of mitotic 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.
The role of the nucleoporin 88 in fetal akinesia
Our genome is isolated by the cell nucleus from the surrounding cellular cytoplasm. Macromolecules that need to shuttle between the cytoplasm and the nucleus are transported through nuclear pore complexes, the gateway of the nucleus. Nuclear pore complexes are massive structures built from distinct proteins, termed nucleoporins.
Intact nucleocytoplasmic transport is crucial for a healthy cell and genetic mutations in nucleoporins have been linked to many human diseases. We found that mutations in nucleoporin 88 (NUP88) lead to the lethal disorder fetal akinesia deformation sequence (FADS). FADS is known to be caused by defect signalling at the neuromuscular junction, the synapse where a motor neuron transmits a signal to a muscle fibre.
To uncover the role of NUP88 in the pathogenesis of FADS we currently investigate cellular behaviour linked to the actin cytoskeleton which can serve as a mechanical model for muscle fibres. We use imaging approaches to see actin in action, particularly in living cells.
Bachelor or master thesis project “chromatin decondensation at the end of mitosis”
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
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:
Dr. Ramona Jühlen
rjuehlenukaachende
Institute of Biochemistry and Molecular Cell Biology
Medical Faculty, RWTH Aachen University
Pauwelsstrasse 30
52074 Aachen
Bachelor or master thesis project "Role of nucleoporin 88 in fetal akinesia"
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.
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
rjuehlen@ukaachen.de
Institute of Biochemistry and Molecular Cell Biology
Medical Faculty, RWTH Aachen University
Pauwelsstrasse 30
52074 Aachen
