Universitätsklinikum Heidelberg: Regulierung der Transkription bei Entwicklungsstörungen (AG Laugsch)

Transcriptional Regulation in Developmental Disorders

News

We are looking for an enthusiastic postdoc to join our research group to study the fate of the MAGE family member L2 (MAGEL2) in human neurons in the context of Prader-Willi Syndrome (PWS) and Schaaf-Yang Syndrome (SYS).

The successful applicant will investigate the underlying molecular defects of SYS and PWS applying hiPSC culture and differentiation, molecular cloning, CRISPR/Cas9 engineering, confocal and high-resolution microscopy, co-immunoprecipitation, Western blot, immunofluorescence. General ability to analyse and integrate multi-omics data bioinformatics is required. Good written and oral communication skills, good organizational and time management skills, and a commitment to excellent record keeping, presentations and conducting rigorous research are a must. Competent supervision of students will be required. The postdoc is expected to collaborate with national and international scientists.

Duration: Eighteen months, starting as soon as possible, at the latest by 01.01.2025

Application deadline: 30.11.2024

The application must include your motivation, a brief statement of your scientific interests, contact details from three references, curriculum vitae, separated publication list, and relevant certificates.

Please forward your complete application in a single pdf document with the filename:

Postdoc_ MAGEL2_ first name_ second name (no other format will be accepted) by e-mail to magdalena.laugsch(at)uni-heidelberg.de

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Congratulations to Michael Eibl who was selected to present his Master Thesis work in the Best Poster Session at the European Human Genetics Conference (ESHG2024, Berlin, Germany). His bioinformatics project is focused on understanding transcriptional regulation in human cranial neural crest cell differentiation by integrating time-course transcriptomic and epigenomic data.

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We look forward to welcoming Stephanie Schofield in the Fall of 2023 after she has won a United States Fulbright to study in our lab. She previously studied antibiotic treatment failure under Dr. Wendy Mok at UConn Health, Farmington, NM, USA and will use this experience to apply to her studies in our lab on developing craniofacial organoids.

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We wish our medical doctoral student Jannis, who elucidates the role of the gene MAGEL2 in human disease, all the best for his semester abroad at the University of California, San Francisco (UCSF). Building on his experience in our lab, he will use CRISPR-based screens in hiPSC-derived neurons and glia cells to investigate the role of the protein tau in dementia.”

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Congratulations to Feven (Biosciences, Julius-Maximilians-Universität of Würzburg) on her advancement award (Förderpreis) of the Hochschulgesellschaft Bonn-Rhein-Sieg for her bachelor thesis 2022, sponsored by “Stiftung Evolution”. During her internship and thesis, Feven generated CRISPR/Cas9 highly valuable models to study Bosch-Boonstra-Schaaf Optic Atrophy Syndrome.

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Congratulations to Ayat on receiving the CMMC Poster Award 2021 at the "25 Years of Progress in Molecular Medicine" symposium held in Cologne, Germany in September 2021. She presented her work about in vitromodeling Bosch-Boonstra-Schaaf Optic Atrophy Syndrome (BBSOAS).

WHO?

WHAT?

We explore the relationship between craniofacial and brain development and their intimate interactions in health and disease.

WHY?

In vertebrates, the head forms from a transient and multipotent population of neural crest cells that appears after the embryonic neural tube closes. From this point onward, head and brain formation are intertwined throughout development. The head protects the developing brain and facilitates its functional integration, and many neurodevelopmental disorders also include craniofacial malformations. Our research focuses on developmental genes that need a specific and dynamic regulation e.g. by enhancers. That regulation ensures establishing their precise expression patterns during development, which might have pathological consequences when being disrupted. In this context, our investigations of the similarities and differences between human neural crest cells and neuronal cells will provide valuable insights into the causes of neurodevelopmental conditions.

HOW?

A great breakthrough in the field of human disease modeling was the possibility to obtain human stem cells by reprogramming adult somatic cells. Since then, these so-called human induced pluripotent stem cells (hiPSC) have been generated from patient donors and then differentiated into disease-relevant cell types that can be used to expand our knowledge about the molecular basis of disease. The power of disease modeling has further expanded with the development of CRISPR/Cas9 technology, which simplifies introducing or correcting mutations in cellular DNA.
Leveraging our expertise in hiPSC culture, genome editing (CRISPR/Cas9), and their directed differentiation (neural and neural crest), we have been recapitulating early human embryogenesis. To analyze that process, we have been combining epigenomic (ChIP-seq, 4C-seq, Hi-ChIP-seq) and transcriptomic data (RNA-seq) with advanced computational approaches. Our genomewide data should provide an excellent foundation for innovative studies on the intimate interactions and relationships between craniofacial and brain development.

Figure 1: Scheme of generation and possible applications of hiPSC. Human cells of any origin can be reprogramed into hiPSC by transient overexpression of a combination of certain transcription factors. Due to their renewing potential, hiPSC can be expanded and engineered. Finally, hiPSC can be differentiated into the desired cell type and applied for disease modelling, drug screening or transplantation.

Join the lab

YOU are a curiosity-driven researcher, passionated for science, have good written and verbal communication skills in English, can work both independently and as part of our team.

WE offer you a creative and inspiring environment of highly enthusiastic and motivated scientists. You will find here an international and multi-disciplinary group and a friendly working atmosphere that supports individual career development. Our team and our outstanding national and international collaborations apply cutting-edge approaches to investigate the craniofacial and brain development using hiPSC models.

MASTER AND BSC. STUDENTS, INTERN STUDENTS

Talented students with a strong interest in stem cell, molecular biology, and bioinformatics are welcome in our laboratory. However, the opportunities strongly depend on our ongoing scientific questions and capacities.

OPEN PHD AND POSTDOC POSITIONS

Currently, there are no open positions available, but excellent candidates are always encouraged to contact Magdalena Laugsch.

SELECTED RECENT PUBLICATIONS

Overarching control of autophagy and DNA damage response by CHD6 revealed by modeling a rare human pathology.
Y. Kargapolova, R. Rehimi, H. Kayserili, J. Brühl, K. Sofiadis, A. Zirkel, S. Palikyras, A. Mizi, Y. Li, G. Yigit, et al.
Nat Commun. 2021 May 21;12(1). doi: 10.1038/s41467-021-23327-1.

Dosage analysis of the 7q11.23 Williams region identifies BAZ1B as a major human gene patterning the modern human face and underlying self-domestication.
M. Zanella, A. Vitriolo, A. Andirko, P. T. Martins, S. Sturm, T. O’Rourke, M. Laugsch, N. Malerba, A. Skaros, S. Trattaro, et al.
Sci. Adv. 2019 Dec 6;5(12). doi: 10.1126/sciadv.aaw7908.

mTOR and autophagy pathways are dysregulated in murine and human models of Schaaf-Yang syndrome.
E. Crutcher, R. Pal, F. Naini, P. Zhang, M. Laugsch, J. Kim, A. Bajic, C. P. Schaaf.
Sci Rep. 2019 Nov 4;9(1). doi: 10.1038/s41598-019-52287-2.

Modeling the Pathological Long-Range Regulatory Effects of Human Structural Variation with Patient-Specific hiPSCs.
M. Laugsch*, M. Bartusel*, R. Rehimi, H. Alirzayeva, A. Karaolidou, G. Crispatzu, P. Zentis, M. Nikolic, T. Bleckwehl, P. Kolovos, et al.
Cell Stem Cell. 2019 May;24(5):736-752.e12. doi: 10.1016/j.stem.2019.03.004.

Functional Restoration of gp91phox-Oxidase Activity by BAC Transgenesis and Gene Targeting in X-linked Chronic Granulomatous Disease iPSCs.
M. Laugsch*, M. Rostovskaya*, S. Velychko, C. Richter, A. Zimmer, B. Klink, E. Schröck, M. Haase, K. Neumann, S. Thieme, et al.
Molecular Therapy. 2016 April;24(4):812-822. doi: 10.1038/mt.2015.154.

* shared authorship

Group members

Group Leader Dr. rer. nat. Magdalena Laugsch
After her diploma studies in biology (University of Braunschweig and University of Cologne), she obtained her Ph.D. degree at the Institute of Pharmacology and Toxicology (University of Magdeburg). For her following career, scientific projects with Prof. Rolf Jessberger (Institute of Biochemistry, Dresden) and Dr. Alvaro Rada-Iglesias (CMMC, Cologne) were crucial. In Prof. Schaaf's lab (2019), she got the great opportunity to study neurodevelopmental disorders related to the neural crest (Institute of Human Genetics, Heidelberg). In 2020, Magdalena became a group leader. Since then, she is expanding her research in this area.

Contact
+49 6221 56-39128
Magdalena.Laugsch(at)uni-heidelberg.de

Aylin Camgöz, PhD (collaboration with Dr. Marcel Kool)
Aylin received her doctoral degree from Frank Buchholz lab at the department of Medical Systems Biology at the University Cancer Center, Dresden. She continues her scientific journey as a postdoctoral researcher in the Pediatric Neuro-oncology department at DFKZ. She currently investigates the function of epigenetic regulators in the initiation and maintenance of pediatric ependymoma.

Ayat Ahmed, MSc, Ph.D. student
Ayat received her Master of Molecular Biology of the Cell at the Faculty of Science and Technology in Milan, Italy and accomplishes her PhD in our lab. Her research focuses on investigating the regulatory landscape of the transcription factor NR2F1 in the neural crest. Besides, she aims to determine the regulatory network controlled by NR2F1 in neural crest and neurodevelopmental disorder.
Email: Ayat.Ahmed@med.uni-heidelberg.de

Susanne Theiß, Technician
Susanne is working on genome organization (4C and Hi-C) and identifying genome-wide DNA binding sites for different transcription factors and histone modifications (ChIP-seq). She supports us in determining changes in regulatory landscapes and networks in various neurodevelopmental disorders. In addition, Susanne is an expert in the field of CRISPR/Cas9 mediated genome editing.
Email: Susanne.Theiss@uni-heidelberg.de

Jannis Bücking, medical student
As a medical student at the University of Heidelberg, Jannis is completing his medical dissertation by studying the neurodevelopmental disorders Prader-Willi and Schaaf-Yang Syndrome. In doing so, he applies the CRISPR/Ca9 technique to knock out genes relevant to the development of the diseases and differentiates hiPSCs into neurons. His transcriptomic, proteomic, and cell biological data will provide a deeper understanding of the role of gene MAGEL2 in the pathogenesis.
Email: Jannis.Buecking@stud.uni-heidelberg.de

Michael Eibl, B.Sc.
Michael is a Molecular Biotechnology Master student at Heidelberg University with a focus on bioinformatics. He is interested in applying bioinformatics methods to questions in neural crest development. During his Master thesis he is analysing time-course transcriptomic and epigenomic data to obtain insights into gene regulatory programs underlying neural crest cell differentiation.

Tobias Walczuch, B.Sc.
As a Master student in Molecular Biomedicine at the University of Münster, Tobias is working on his Master thesis about the MAGEL2 protein and its contribution to human diseases. He employs our CRISPR/Cas9 cell models, molecular biology techniques as well as high-resolution microscopy

Maren Gehringer, B.Sc.
Maren is a second-year Master's student in Molecular Biosciences Infectious Diseases at the University of Heidelberg. During her internship, she analyses embryoid bodies using confocal microscopy. These 3D organoids are formed from hiPSC and give rise to hNCC.

Marie Körner, B.Sc.
Marie is a Master's student of Molecular Biotechnology at the University of Heidelberg. During her internship and the following Master's thesis, she is investigating the regulatory role of NR2F1 enhancers in the neural crest and during neurodevelopment.

Asimenia Pitsini
As a Bachelor's student in Biomedical Sciences at the University of West Attica, Greece, Asimenia is pursuing an internship in our lab for the spring semester 2024. Utilizing different CRISPR/Cas9 techniques, she is supporting us in the generating of different hiPSC lines required for unravelling the NR2F1 gene regulation.

Stephanie Schofiled, B.Sc.
Stephanie received her bachelor degree in Molecular and Cell Biology at the University of Connecticut in the United States and joined AG Laugsch as a research grantee under the Fulbright Germany U.S. Student Program in September 2023. She is currently working towards establishing 3D craniofacial and neural organoids to study developmental implications of Cornelia de Lange Syndrome.

Alumni

Léa Franchitti, intern (Spring-summer 2023) Master's student in Health Biology at the University of Rouen, France

Melissa Flassig, intern (Summer 2023) Master's student of biochemistry at the University of Heidelberg.

Malina Reisch, (2023) Bachelor thesis in pharmaceutical biotechnology at Biberach University of Applied Sciences.

Tatyana Kan, B.Sc, intern (Spring-Summer 2023), Master's student in Molecular Biosciences at Heidelberg University.

Ruiyuan Zheng, Dr. rer. nat., Postdoc (November 2022-September 2023)

Cao Ding, MSc, student in the doctor of medicine program (2020-2023), collaboration with Dr. Christina Eichstaedt

Tobias Beschauner, B.Sc, intern (Winter 2022-Summer 2023), Master's student of Biochemistry at the University of Heidelberg.

Freya Herrmann-Sim, intern (Summer- Autumn 2022, undergraduate student of biosciences at the University of Heidelberg)

Büşranur Çeltik, intern (Summer- Autumn 2022, Genetics and Bioengineering at Izmir University of Economics in Turkey)

Stella Bähr, B.Sc. intern (Autumn-Winter 2022, master's student of Molecular Biotechnology at the University of Heidelberg, with a focus on Bioinformatics)

Ragini Gabhrani, B.Sc. intern (Autumn-Winter 2022/2023, master's student of Molecular Biotechnology from the Anhalt University of Applied Sciences)

Aaron Sievers, M.Sc, biophysicist (2021/2022, support with bioinformatic analysis)

Feven Berhanne, (intern and bachelor thesis 2022, Applied Biology at the University of Applied Sciences Bonn-Rhein-Sieg in Rheinbach)

Luis Castillo, technician (2021/2022, supported us as a technical assistant in the laboratory)

Tamara Schmidt, B.Sc, intern (Winter/Summer 2022, Biochemistry Master studies, University of Heidelberg)

Leonie Schumacher, intern (Spring/Summer 2022, Villingen-Schwenningen University Gemany)

Mara Rudigier, intern (bachelor thesis 2022, Villingen-Schwenningen University Gemany)

Melanie Spanjaard, medical student (medical dissertation 2022, University of Heidelberg)

Kristina Krank, B.Sc (intern, June-November 2021, Biochemistry Master studies, University of Heidelberg

Arya Lal Erkilinçoğlu, (intern, Summer 2020, student of Yeditepe University, Istanbul, Turkey)

Sarah Cluff, MSc (master thesis, July 2021, Molecular Cellular Biology, University of Heidelberg)

Marc Thomas, B.Sc (intern, Spring 2021, Biochemistry Master studies, University of Heidelberg)

Alexander Wirth, B.Sc (intern, 2020/2021, Biochemistry Master studies in University of Heidelberg)

Rocio Olmos Romero, M.Sc (master thesis, December 2020, Translational Medical Research, University of Heidelberg)

Forschung