Project focuses on studying the function of chromatin remodeling ISWI ATPase Smarca5 (Snf2h, MommeD4, Iswi) in the development of haematopoiesis from stem and progenitor cells and to understand their involvement in leukaemogenesis. Chromatin, a nucleoprotein complex engaged in the transfer of biological information, is made accessible (or inaccessible) upon activities of enzymes that belong to SWI/SNF2 family.
SWI/SNF2 proteins, namely Smarca5, can regulate the interaction between DNA and histones and allow or block cell decisions imposed by recruitments of these factors. Importantly, Smarca5 interacts with several hematopoietic transcription factors, whose role is also a focus in our plans, as well as to understand target genetic programs of Smarca5-complexes.
- To understand mechanisms that during development are involved in regulating cell fate decisions at the level of chromatin and Smarca5.
- To elucidate role of Smarca5 in lineage-specific processes involving differentiation and lineage commitment using proposed set of transgenic animals that enable tissue specific knockout and overexpression.
- To understand how disruption of mechanisms involving Smarca5 and their partners may lead to haematologic malignancies.