The working group of “Alternative method development for environmental toxicity testing” led by Prof. Ellen Fritsche is looking for a student (f/m/d) for a Master Thesis with the title:
Impact of genotoxins on human neurodevelopmental processes in vitro
The project: The development of the human brain is based on a variety of strictly regulated and time-dependent processes up to young adulthood. Early stages of brain development are characterized by extensive proliferation of human neural stem- and progenitor cells (NSPCs), which later on differentiate into neurons, oligodendrocytes and astrocytes. Furthermore, apoptosis is a key hallmark of human brain development as a large proportion of generated cells die during development. DNA-damaging substances can potentially disturb the balance of these processes by causing mutations that induce apoptosis, disturb differentiation or inhibit cell proliferation.
The type of DNA damage and therefore also the necessary DNA repair mechanism can thereby differ depending on the substance. However, the extent to which human NSPCs can be damaged by genotoxic substances and how their vulnerability changes during development have not been well studied. Since the developing cell types of the brain are of high longevity and their self-renewal capacity is limited during adulthood, it is particularly important that DNA repair is error-free. Exposure of pregnant women to cigarette smoke for example can lead to an increased rate of DNA adducts in umbilical cord blood and to impaired cognitive development of exposed children.
Within the ‘Neurosphere Assay’, a primary in vitro cell culture model based on human neural progenitor cells, which mimics a variety of neurodevelopmental processes, e.g. NSPC proliferation, migration and differentiation into neural effector cells (astrocytes, neurons and OL), we already identified distinct effects of four different genotoxins. The quality and magnitude of effects thereby differ depending on the substance, treatment time point and the affected cell types.
To gain a better understanding of the different susceptibility toward genotoxins, this project is orientated to unravel their underlying molecular mechanisms. Therefore, immunocytochemical staining and gene expression analyses of DNA damage response and DNA repair proteins will be performed. Moreover, human induced pluripotent stem cell (hiPSC) derived NSPCs will be used to also study the effects during an earlier developmental time point (e.g. embryonic development). The results of these studies will contribute to a deeper understanding of developmental stage and cell type-specific susceptibility towards genotoxins during human brain development.
Your profile: Our working group is looking for a motivated employee with a high level of commitment, fun at work, motivation, communication skills and team spirit. The applicant should have a completed bachelor’s degree in life sciences. An additional (master) training in the field of toxicology or pharmacology is a plus. Hands on experience in cell culture is desirable. Furthermore, good knowledge of English is mandatory.
We offer: We are an interdisciplinary, international team with a pleasant working atmosphere. We offer thorough training in a highly topical, challenging area of research. The project is part of the RTG2578 “Impact of genotoxins on the differentiation efficacy of murine and human stem and progenitor cells and functional competence of thereof derived differentiated progeny”, for more information go to: https://www.grk2578.hhu.de/en/.
Start: As early as possible.
Please address your application (short letter of motivation, CV, qualification certificates) with the reference number “RTG2578” in the subject line as one summarized document in PDF format by e-mail to firstname.lastname@example.org:
Prof. Ellen Fritsche
IUF – Leibniz-Institut für umweltmedizinische Forschung
Auf’m Hennekamp 50
Application documents submitted by post are not returned. Documents for applicants not considered are destroyed appropriately once the procedure is complete.