C04: Cellular differentiation in brain tissue-like matrices

C04 aims at using cell types with the same embryonic origin but distinct differentiation than brain cells, melanocytes and melanoma cells, to analyse the role of mechanics on cellular differentiation and de-differentiation. Melanocytes originate from the neural crest and display several characteristics typical of neural cells such as Schwann cells. Interestingly, melanoma cells are known to have the feasibility to transdifferentiated into Schwann cells (‘Schwannian differentiation’). Comparison of cells from melanocytic origin to neural cells with regards to the impact of the different microenvironmental matrices on differentiation is therefore highly interesting. Further, melanoma cells actively metastasise into the brain in a high percentage of patients. Understanding of this process resembles a strong clinical need as brain metastases of melanoma are still not curable. We will analyse melanocytes or melanoblast-related cells (de-differentiated melanocytes) in decellularised brain tissue or brain tissue-mimicking matrix and will use a detailed molecular characterisation (e.g., differentiation specific genes (MITF, Pax3) and senescence markers, RNASeq and bioinformatical analyses) to define the brain-tissue-specific cell behaviour and differentiation. By modelling of the matrix, its defined influence on molecular characteristics will be analysed. In addition, molecular features and tumor cell characteristics of melanoma cells in brain tissue-mimicking hydrogels or decellularised brain tissue will be studied in detail to get insight into brain metastases of this aggressive tumor. We finally aim at understanding whether differentiation cues are mediated via biomechanics and further, whether the brain is an attractive soil for melanoma cells due to its mechanical properties.

Project leader: Prof. Dr. Anja Bosserhoff

Positions: 1 doctoral researcher