topological organization of transcriptional activation during motor neuron development

Justin Demmerle

In collaboration with the Macfarlan Lab at the National Institutes of Health, we are studying the topological organization of transcriptional activation during motor neuron development. In a mouse embryonic stem cell system, we can induce motor neuron identity, and observe the formation of cell-type specific transcriptional activating complexes. Using 3D-SIM and custom-built image analysis tools, we can observe on nanometer scales the spatial relationships between different components of the activating complex. We intend to expand this analysis to DNA and RNA, as well as proteins, in order to construct physiological distance maps of transcriptional activation in both wildtype and mutant motor neuron development. This work will be combined with biochemical methods (ChIP-Seq, ChIA-PET, Capture-C) to create models of 4-dimensional nuclear organization and chromatin remodeling at specific loci regulating motor neuron identity.


ABOUT

Justin graduated from the University of Chicago with a B.A. in biology, concentrating in Molecular & Cellular Biology, in 2011. Interested in the functional organization of the nucleus since his first year, he worked on mechanisms of chromatin remodeling at the inner nuclear membrane and gene positioning dynamics in muscle stem cells in James Holaska’s laboratory at the University of Chicago from 2010-2013. Wanting to explore nuclear organization and epigenetic function further, he joined the Schermelleh Lab in 2013 as a Research Assistant, helping to establish the lab and improving the application of 3D-SIM to questions of chromatin biology. He won a NIH-Oxford-Cambridge Scholars Program PhD Scholarship in 2014, and now collaborates between the Schermelleh Lab and the laboratory of Mammalian Epigenome Reprogramming, headed by Todd Macfarlan, in the National Institute of Child Health & Human Development at the National Institutes of Health in Bethesda, MD. He hopes to combine super-resolution microscopy, traditional biochemistry, and next-generation sequencing approaches to create holistic topological maps of chromatin remodeling during development.

Justin.Demmerle@bioch.ox.ac.uk