Humangenetik

Transcriptional Regulation in Developmental Disorders

PhD/Postdoc position in computational biology to elucidate NRF2F1 dosage dependent regulatory networks in health and disease (d/f/m)

We are looking for an enthusiastic Postdoc/PhD to join our research group to study gene regulation in neurodevelopment with a focus on how NR2F1 dosage shapes the specification of neuronal lineages and the formation of cortical circuits.
NR2F1 is a key transcription factor controlling embryonic neuronal development. Mutation and deletions of NR2F1 lead to Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS). Using neuronal cells derived from CRISPR/Cas9 engineered human induced pluripotent stem cells (hiPSC) we model distinct NR2F1 dosages to study their effects across neuronal differentiation. By integrating time-resolved bulk (RNA-seq, ATAC-seq, ChIP-seq, Hi-C) obtained from in neuronal lineages cultured in 2D cells and single-cell multi-omics (scRNA-seq, scATAC-seq, Multiome) data generated in 3D forebrain dorsal organoids, we aim to map regulatory networks sensitive to NR2F1 expression levels.
Our group studies the fundamental principles of embryonic neuronal development by combining genomics, gene editing, and bioinformatics. We offer an international, dynamic, and supportive research environment that fosters creativity and career growth. The AG Laugsch is embedded within Heidelberg’s excellent computational biology network, fostering close collaborations with experts like Carl Herrmann (Institute of Pharmacy and Molecular Biotechnology), and Julio Saez-Rodriguez (Systems Biomedicine, Institute of Computational Biomedicine. If you are a curiosity-driven researcher who enjoys interdisciplinary teamwork and tackling complex biological questions through data, we would be delighted to hear from you. 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.

https://www.klinikum.uni-heidelberg.de/humangenetik/forschung/ag-laugsch/

Literature
https://doi.org/10.64898/2026.06.25.734423 
https://doi.org/10.64898/2026.05.01.722223 
doi: 10.1016/j.stem.2019.03.004. 

Your profile: 

• Strong background in bioinformatics or computational biology
• Practical experience with omics data pre-processing, pipeline development, and high-performance computing
• Proficiency in R or Python, and shell scripting
• Interest in gene regulation and developmental biology
• Optional previous experience with epigenomic data analysis or gene regulatory network inference
• Ability to work independently and collaboratively in a multidisciplinary environment
• Excellent written and spoken English skills

Your profile: 

  1. Establish computational pipelines for the analysis and integration of single-cell multi-omics data (scRNA-seq, scATAC-seq, Multiome) to reconstruct gene regulatory networks in 3D forebrain dorsal organoids to determine pathophysiological consequences of aberrant NR2F1 dosage.

  2. Design and build an interactive, open-access web platform for visualization and usage of multi-omics datasets

  3. Integrate newly generated data with in-house and publicly available datasets to interpret results in a robust biological context

  4. Ensure reproducibility, data management, and documentation of computational workflows in high-performance computing environments

  5. Collaborate closely with experts in computational biology across the university and affiliated institutes, as well as with experimental researchers (wet lab) in the AG Laugsch, to support accurate data interpretation and integration.

  6. Maintain clear documentation of analyses and computational workflows on eLab and provide regular progress reports and updates.

  7. Actively participate in regular journal clubs and institute meetings. Present findings at lab meetings and international conferences and contribute to manuscripts and grant applications.

Application deadline: 31.08.2026

Please forward your complete application in a single pdf document with the filename: 2026_multiome_ first name_ second name (no other format will be accepted) by e-mail to: 

magdalena.laugsch@uni-heidelberg.de

News

We wish our medical doctoral student Jannis, much of success during his second semester abroad at Harvard University and Boston Children's Hospital, where he is learning performing an analyzing snRNA-seq in the human postmortem hippocampus to investigate the role of somatic mutations in Neurofibromatosis type 1. These new skills will further strengthen his methodological toolkit for studying SYS and PWS neurons. 

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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, CRISPR/Cas9 engineering, and their directed differentiation into 2D cells and 3D organoids we have been recapitulating early human embryogenesis. To analyze the complex developmental processes, we combine epigenomic approaches (ChIP-seq, 4C-seq, Hi-ChIP), transcriptomic data (bulk RNA-seq), proteomics, ubiquitinomics, and phosphoproteomics, as well as single-cell multi‑omics including scRNA-seq, scATAC-seq, and Multiome, with advanced computational methods.

Our genome-wide, time-resolved data allow us to explore how variants in non‑coding regulatory elements (accounting for ~99% of the genome) control key developmental genes and contribute to disease. By identifying altered regulatory networks and pathways, we aim to deepen the understanding of disease mechanisms, improve genotype-phenotype correlations, and uncover variants that contribute to a broad spectrum of neurodevelopmental disorders. Our goal is also to provide an excellent foundation for innovative studies on human disease, including the intimate interactions between craniofacial and brain development. We strongly believe that our data will open new avenues for developing and improving treatment strategies and for expanding molecular diagnosis in human developmental disorders.

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

A non-syndromic orofacial cleft risk locus links tRNA splicing defects to neural crest cell pathologies
Bartusel M, Kim SX, Rehimi R, Darnell AM, Nikolić M, Heggemann J, Kolovos P, van Ijcken WFJ, Varineau J, Crispatzu G, Mangold E, Brugmann SA, Vander Heiden MG, Laugsch M, Ludwig KU, Rada-Iglesias A, Calo E
Am J Hum Genet. 2025 May 1;112(5):1097-1116. doi: 10.1016/j.ajhg.2025.03.017. Epub 2025 Apr 17. PMID: 40250422; PMCID: PMC12120183.

Unravelling the conundrum of nucleolar NR2F1 localization using antibody-based approaches in vitro and in vivo
Bertacchi M, Theiß S, Ahmed A, Eibl M, Loubat A, Maharaux G, Phromkrasae W, Chakrabandhu K, Camgöz A, Antonaci M, Schaaf CP, Studer M, Laugsch M.
Commun Biol. 2025 Apr 10;8(1):594. doi: 10.1038/s42003-025-07985-1. PMID: 40204944; PMCID: PMC11982218.

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, Magdalena.Laugsch@uni-heidelberg.de 

After her diploma study 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, Medical Faculty). She continued working on projects with medical relevance at Institute of Biochemistry, Dresden with Rolf Jessberger, and university of Cologne with Alvaro Rada-Iglesias. In 2020, Magdalena became a group leader at the Institute of Human Genetics in Heidelberg, elucidating transcriptional regulation and protein homeostasis in health and disease. 

 

Atefeh Harsij, Ph.D. junior scientist, Atefeh.Harsij@med.uni-heidelberg.de

Atefeh obtained her Master’s degree in Human Genetics from Shahid Beheshti University of Medical Sciences in Tehran, Iran and is elucidating the role of cohesin on human head and face development. Specifically, she aims to investigate how cohesin influences chromatin 3D organization, regulatory networks in craniofacial neural crest cells, and gene expression in the context of Cornelia de Lange syndrome (CdLS) using Hi-ChIP and RNA-seq.

 

Ayat Ahmed, MSc, Ph.D. student Ayat.Ahmed@med.uni-heidelberg.de

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 and cortical neurons to determine dosage-dependent NR2F1 targets affected in Bosch-Boonstra-Schaaf Optic Atrophy Syndrome (BBSOAS).

 

Baran Enes Güler, Dr. rer. nat., BaranEnes.Gueler@med.uni-heidelberg.de

Baran earned his doctoral degree in Molecular Cell Biology at Johannes Gutenberg University, Mainz in the Uwe Wolfrum Group deciphering the role of the adhesion in brain astrocytes. As a postdoctoral researcher he investigates the phenotypic similarities and differences between two neurodevelopmental disorders, Schaaf-Yang Syndrome (SYS) Prader-Willi Syndrome (PWS) to determine the role of the MAGEL2 protein in their underlying molecular mechanisms.

 

Camilla Viola, Ph.D. student camilla.viola@mondino.it

Camilla is a visiting PhD student from the University of Pavia (Italy). Her main goal is to develop different familial Amyotrophic Lateral Sclerosis models to study its pathophysiology. In Heidelberg, she uses CRISPR-Cas9 techniques to generate hiPSC lines with disease-relevant point mutations, which will be differentiated into spinal cord organoids and analysed by scRNA-seq.

 

Jannis Bücking, Jannis.Buecking@med.uni-heidelberg.de

As a medical student at Heidelberg University, Jannis is completing his medical dissertation, using neurons derived from various CRISPR/Cas9-modified hiPSC modelling SYS and PWS. He is currently analysing multi-omics data to gain a deeper understanding of the role of the MAGEL2 gene in pathogenesis.

 

Katalin Maricza, Ph.D. student katalin.maricza@stud.uni-heidelberg.de 

Katalin is a visiting PhD student from the Semmelweis University in Budapest, Hungary, where she previously obtained her medical degree. To investigate craniofacial phenotype of CdLS, she is generating hiPSC lines with disease relevant point mutations using CRISPR-Cas9 system to investigate their role in the pathomechanism.

 

Maren Gheringher, Ph.D. student Maren.Gehringer@med.uni-heidelberg.de

Maren is a PhD student working on BBSOAS in dorsal forebrain organoids. Her work focuses on elucidating the NR2F1 orchestrated gene regulatory networks using multi-omics sequencing approaches.

 

Sam Jurriaans, B.Sc., intern s2.jurriaans@student.vu.nl

As a Master’s student at the Vrije Universiteit Amsterdam, Sam is currently completing an internship in our lab, exploring the genetic mechanisms underlying BBSOAS. He aims to extend our CRISPR-Cas9 engineered panel of hiPSC lines modelling BBSOAS to investigate the impact of NR2F1 regulatory elements to the pathomechanism.

 

Susanne Theiß, Susanne.Theiss@med.uni-heidelberg.de 

Susanne is working as technician on genome organization (4C and Hi-C) and identifying genome-wide DNA binding sites for different transcription factors and histone modifications (ChIP-seq).  As an expert on hiPSC culture and differentiation, she employs 3D organoids to determine changes in regulatory landscapes and networks in various neurodevelopmental disorders. In addition, she manages the organization in the laboratory. 

 

Zvonimir Marelja, Dr. rer. nat., Zvonimir.Marelja@med.uni-heidelberg.de

Zvonimir, obtained his PhD degree in biochemistry at the University of Potsdam in the lab of Silke Leimkühler and worked as a postdoctoral researcher on rare monogenetic kidney disorder in Paris and Heidelberg with Matias Simons. He now studies how cohesin dysfunction affects gene regulation and cellular function in hiPSC-derived cranial neural crest cells and cortical neurons using cohesin-dosage and CdLS models.

Alumni

Michael Eibl, M.Sc., intern, master thesis, junior scientist (2023-2025), Molecular Biotechnology, University Heidelberg

Marie Körner, M.Sc, intern, master thesis (2024-2025), Molecular Biotechnology, University Heidelberg

Sevval Yilmazer, Erasmus intern (Summer 2025), science Faculty, Bilkent University, Ankara, Türkiye

Aylin Camgöz, Dr. rer. nat.; Postdoc 2022-2024 (Alliance Postdoc Program in collaboration with Dr. Marcel Kool), University Heidelberg/DKFZ

Asimenia Pitsini, intern (Erasmus Program, Spring/Summer 2024), Bachelor's student Biomedical Sciences at the University of West Attica, Greece

Stephanie Schofiled, B.Sc., intern, Fulbright Germany U.S. Student Program (2023-2024), Molecular and Cell Biology at the University of Connecticut in the United States

Ozennur Unal, Erasmus intern (Summer 2024), Yeditepe University, Istanbul, Türkiye

Tobias Walczuch, M.Sc, intern, master thesis (2023-2024), Molecular Biomedicine at the University of Münster

Stella Bähr, M.Sc., intern (Winter 2022), Molecular Biotechnology, University Heidelberg

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)