To promote cutting-edge technologies to interrogate epigenetic and proteomic changes at the single cell and single locus resolution.
The enabling technology will facilitate the elucidation of fundamental mechanisms of cell heterogeneity that offers translational potential for interrogating rare cell populations.
Over the last twenty years, the ability of profile chromatin states in populations of cells has revolutionized research in the biological sciences. More recently, single-cell transcriptional profiling technologies have demonstrated considerable gene expression heterogeneity in seemingly uniform populations of cells. These differences are postulated to underlie cell fate decisions both during normal and diseased development.
Transcriptional changes accompany alterations in chemical modifications of chromatin. A subset of these chromatin modifications is thought to precede and cause the observed transcriptional changes. The field of epigenetics is currently grappling with the key question of which chromatin marks underlie defined transcriptional states. Not unexpectedly, the data suggest that specific chromatin marks play both cell type- and locus-specific roles in epigenetic transcriptional regulation. To fill this gap in knowledge, we outline a set of long-term goals below. We envision that accomplishing these goals would benefit many groups at Michigan Medicine and the University of Michigan broadly.
- To organize a campus-wide Chromatin Club (initially to meet once every two weeks, with the possibility to expand to once/week with sufficient membership).
- To develop technologies to dissect epigenetic plasticity in intact tissues of mice.
- To develop the capacity to purify the components and to define the structures of nucleosome-nucleosome regulatory complexes isolated in their native state.
- To develop/implement technologies to profile epigenomic marks at single cell resolution.
- To develop/implement technologies to identify the suite of epigenetic factors and their accessory proteins at locus-specific resolution.
- To develop/implement technologies to manipulate the epigenome at cell- and locus-specific manner.
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