Kliniken & Institute … Institute Institute of Human… Research Department of Human… AG Laugsch

AG Laugsch

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

If you wish to work on hiPSC differentiation towards neural crest or neuronal lineages and their characterization, e.g., by RNA and ChIP-seq, please contact Magdalena Laugsch.

Currently, we are looking for talented students with a keen interest in stem cell and molecular biology to work on a master thesis in our laboratory. Two different topics are available: 

  1. Generation of CRISPR/Cas9 engineered in hiPSC lines for disease modeling.
  2. Neuronal differentiation of hiPSC.

OPEN POSITIONS

There is a Ph.D. position available to elucidate the transcriptional regulation upon hNCC differentiation in health and disease. We are seeking a highly motivated and self-driven student with a completed Master-Degree in biology, biochemistry, or related disciplines with laboratory experience. For more details, please visit: https://www.jobvector.de/jobs-stellenangebote/biologie-life-sciences/wissenschaftliche-r-mitarbeiter-in/ph-d-student-at-institute-human-genetics-138741.html

Technical assistance position in part-time 50% available
https://karriere.klinikum.uni-heidelberg.de/stellenangebot/11170/Technical-assistance-position-%28m%7Cf%7Cd%29.html

SELECTED RECENT PUBLICATIONS


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
Tel. +49 6221 56-39128
E-Mail: Magdalena.Laugsch@uni-heidelberg.de

Master Student:
Rocio Olmos Romero
CRISPR/Cas9 mediated genome editing in hiPSC
Tel. +49 6221 56-5072
E-Mail: Rocio.Olmos-Romero@med.uni-heidelberg.de