Institute of Human… Research Transcriptional…

Transcriptional regulation in developmental disorders (AG Laugsch)

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.


Kargapolova Y, Rehim R, Kayserili H, Brühl, ZirkelA, Li Y, Yigit, G, Hoischen A, Frank S, Russ N, Trautwein J, Laugsch M, Gade Gusmao E, Josipovic N, Altmüller J, Nürnberg P, Kaiser FJ, Wartin E, Brunner H, Rada-Iglesias A, Kurian L, Wollnik B, Bouazoune K, Papantonis A. Overarching control of autophagy and DNA damage response by CHD6 revealed by modeling a rare human pathology. doi: https://doi.org/10.1101/2020.01.27.921171

Zanella M, Vitriolo A, Andirko A, Tiago Martins P, Sturm S, O’Rourke T, Laugsch M, Malerba N, Skaros A, Trattaro S, Germain P, Mihailovic M, Merla G, Rada-Iglesias A, Boeckx C, Testa G (2019). Dosage analysis of the 7q11.23 Williams region identifies BAZ1B as a major human gene patterning the modern human face and underlying self-domestication. Sci Adv. 2019 Dec 4;5(12):eaaw7908.

Crutcher E, Pal R, Naini F, Zhang P, Laugsch M, Kim J, Bajic A, Schaaf CP. (2019) mTOR and autophagy pathways are dysregulated in murine and human models of Schaaf-Yang syndrome. Sci Rep. 9(1):15935.

Laugsch M*, Bartusel M*, Rehimi R, Alirzayeva H, Karaolidou A, Crispatzu G, Zentis P, Nikolic M, Bleckwehl T, Kolovos P, van Ijcken WFJ, Šarić T, Koehler K, Frommolt P, Lachlan K, Baptista J, Rada-Iglesias A (2019). Modelling the pathological long-range regulatory effects of human structural variation with patient-specific hiPSCCell Stem Cell. 5, 736-752.

Laugsch M*, Rostovskaya M*, Velychko S, Richter C, Zimmer A, Klink B, Schröck E, Haase M, Neumann K, Thieme S., et al. (2016). Functional Restoration of gp91phox-Oxidase Activity by BAC Transgenesis and Gene Targeting in X-linked Chronic Granulomatous Disease iPSCs. Mol. Ther. 4, 812-22.

* 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 Rda-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

Leonie Schumacher, BSc
Leonie Schumacher has completed her bachelor's degree in Molecular and Technical Medicine at the Hochschule Furtwangen University in Germany. Before starting her master's program at the Radboud University, Nederlands, she is deepening her scientific knowledge during an internship with us and investigating the effects of transient knockdown of different cohesin subunits on neural crest cells.

Mara Rudigier, intern
Mara is studying molecular and technical medicine in the bachelor's program at Villingen-Schwenningen University and joined our lab on the 1st of March 2021 for an internship. Her goal is to investigate the molecular causes of craniofacial abnormalities in human disease. She employs CRISPR/Cas9 technique in hiPSC to generate a conditional knockout of genes relevant to the differentiation of neural crest cells.

Ayat Ahmed, MSc
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

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 syndrome 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 iPSCs into neurons.
Email: Jannis.Buecking@stud.uni-heidelberg.de

Tamara Schmidt, BSc
After completing her bachelor's degree in biochemistry at the University of Heidelberg, Tamara is pursuing her master's degree in biochemistry. She recently joined our lab and will use CRISPR/Cas9 technology in hiPSCs to knock out different subunits of the cohesin complex.
Email: Tamara.Schmidt@stud.uni-heidelberg.de

Feven Berhanne, intern
Feven is studying Applied Biology at the University of Applied Sciences Bonn-Rhein-Sieg in Rheinbach and joined the lab in September 2021 for an internship and her bachelor thesis. Using CRISPR/Cas9 mediated genome editing, she generates hiPSC lines with deletion of the putative regulatory elements of NR2F1 to expand our tools for disease modelling.

Luis Castillo, PhD
Luis supports hiPSC-differentiation towards neural crest cells and neurons, general lab management tasks, as well as epigenetic, transcriptomic, and functional analysis of our cell models.
Email: Luis.Castillo-Ramirez@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

Aaron Sievers, MSc
Aaron is a biophysicist working on in silico studies of DNA-sequence-dependent physiochemical properties of chromatin. He is responsible for bioinformatic analysis.
Email: Aaron.Sievers@med.uni-heidelberg.de

Cao Ding, MSc (collaboration with Dr. Christina Eichstaedt)
Cao is a student in the doctor of medicine program. He investigates the functional effect of genetic variants of pulmonary arterial hypertension patients.
Email: Cao.Ding@med.uni-heidelberg.de

ALUMNI:

Melanie Spanjaard, medical student (medical dissertation 2021, University of Heidelberg)

Kristina Krank, BSc (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, BSc (intern, Spring 2021, Biochemistry Master studies, University of Heidelberg)

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

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

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