Synthetic cell-based patterning systems and their applications in stem cell differentiation

he haematopoietic system serves as a paradigm for understanding cellular hierarchies and properties of tissue-specific stem cells. Haematopoietic and Leukaemic Stem Cells (HSCs, LSCs) constitute the pioneering models for understanding aspects of both physiological and malignant stem cell biology, making the bone marrow and blood the ideal models to study tissue repair and neoplasia. Albeit constituting the best characterized somatic and cancer stem cells respectively, there is still no clear understanding of the gene regulatory networks that regulate physiological haematopoiesis, and how these are corrupted during leukaemogenesis. I am most interested in dissecting the logic and the nature of these networks in haematopoiesis and how their constituent factors are affected by external conditions, such as niche-derived signals and particularly hypoxia. Characterizing such networks and/or the effect of extrinsic conditions shall substantially contribute in understanding HSC fate-decisions, which might provide insights into the expansion of HSCs ex vivo as well as into the underlying mechanisms of leukaemogenesis, whose hallmark is the deregulation of HSC fate-decisions.

Understanding and recreating (or vice versa) a natural stem cell niche and/or tissue is an integral part of stem cell biology and regenerative medicine. Recreating the bone marrow niche might provide a steady platform to expand HSCs ex vivo. In theory, such synthetic system should provide a platform to study the biology of HSCs, a reliable method to generate sufficient HSC yields for curative transplantations, and an in vitro pharmacological screening system which can provide novel insights into targeting the LSC niche. Due to the tissue complexity of the bone marrow and given that synthetic morphology is a very young field, building and understanding simpler systems is of primary priority. To achieve this, I would be keen on i) investigating known genes in the induction of morphogenic modules, ii) link and coordinate specific modules into certain sequence and iii) establish a link between such modules and core principles of developmental biology (e.g. Turing's system). Such complex genetic engineering would be sufficient to generate, at least in theory, simply patterned tissues, but would also provide a platform to generate more complex morphogenesis.