Zbtb11-mediated molecular mechanisms impacting haemopoietic stem cell function

The blood system is constantly being renewed and increased production of particular blood cell types is required to respond to different diseases or injury. This occurs via the haemopoietic stem cell (HSC) under instruction of molecular and cellular pathways. Transcription factors bind DNA to control how much of a specific gene will be made into protein. Understanding how transcription factors work to maintain a normal population of HSCs and a balanced output of the mix of different mature blood cell populations is central to our understanding of how to manipulate blood cell outputs in the clinic to treat disease.

Our Zbtb11-deficient zebrafish mutant has shown that Zbtb11 is required for HSC maintenance and/or survival. Using Next Generation Sequencing technologies, in vivo genetic and pharmacological manipulation of candidate pathways and biochemical assays this project aims to understand the downstream target genetic and biochemical pathways that are regulated by Zbtb11 and result in loss of HSCs in both zebrafish and mammals.