What is neural stemness? Why is it important? What are the molecular signatures of neural stemness?...

• What is neural stemness?• Why is it important?• What are the molecular

signatures of neural stemness?

• What are the regulatory networks that control neural stemness?

Neural stemness

“Bottom-up” – single gene (REST)•Map genome binding sites•Map loci that are transcriptionally and/or epigenetically regulated•Knock gene out in cells and mice & look at effect on ‘function’•But – which aspects of transcriptional and epigenetic regulation are critical to this function?

Looking for networks“Top-down” – networksIsolating defined regulatory modules

Inferring regulatory modules

Challenges• “Bottom-up”: what does a network

look like from a single gene’s point of view

• “Top-down”: what does a network look like from a global point of view

• Integrate all the ‘omes to enable a network to include knowledge of the transcriptome, epigenome and proteome

• Find a way to conceptualise, model and test such networks

• Prove the value by manipulating a neural stem cell at will to any desired outcome