Uncovering the Proteomic Radial organization within the Eukaryotic Nucleus

Recent evidence gathered in the Bienko Lab indicates that, in addition to DNA, many nuclear proteins including several transcription factors implicated in cell fate determination are non-randomly radially distributed in the nucleus of mammalian cells.

This fascinating observation led me to hypothesize that there exist a broad set of nuclear proteins that are arranged along radial gradients in the nucleus, acting as readers of the radial genome architecture.

Within this MSCA Postdoctoral Fellowship, I aim at tackling this exciting hypothesis by addressing the following fundamental questions: (i) How are nuclear proteins radially arranged in the nucleus of cells undergoing differentiation towards opposing lineages? (ii) What drives and maintains different radial patterns of proteins in the nucleus? (iii) Is the radial arrangement of proteins in the nucleus functionally relevant?

To address these central questions I will first develop an innovative tool to map the spatial arrangement of nuclear proteins radially.

I will then apply the newly developed method to chart the radial nuclear proteome in human induced pluripotent stem cells (iPSCs) undergoing differentiation towards different lineages.

Finally I will explore the functional implications of the radial organization of nuclear proteins by attempting to rewire nuclear radiality and assessing the effects on gene expression and cell identity.

This clearly interdisciplinary project aims at finding an explanation in the spatial organization of the genome and the nuclear proteome to a key question arising from cell and developmental biology: how lineage-specific gene expression programs are set up?

With this ambitious proposal I will dive into the exciting field of 3D genome organization while addressing a completely new hypothesis and potentially making ground-breaking discoveries.