4:00 PM - 5:00 PM
Mapping protein-DNA interactions to study meiotic recombination and single-cell genome organization
A Special Seminar with Nicolas Altemose
This event is co-hosted by the Genetics Department and the Department of Biomedical Data Science.
Speaker: Nicolas Altemose, D.Phil., Department of Bioengineering, UC Berkeley
Abstract: Complex life depends on carefully programmed protein-DNA interactions that read, regulate, repair, replicate, and recombine the DNA within each cell. Mapping the binding sites of specific proteins across the genome can provide key insights into the functions and dynamics of these life-sustaining protein-DNA interactions. For example, by mapping the genome-wide binding sites of PRDM9, a protein that initiates meiotic recombination, I helped to illuminate the complex mechanisms by which this rapidly evolving protein contributes to speciation in mice. However, conventional sequencing methods for mapping protein-DNA interactions require bulk populations of cells as input, which can obscure processes that occur uniquely within individual cells, such as those involved in meiotic recombination. To address this limitation, I began developing methods for mapping protein-DNA interactions in single cells. Specifically, I engineered a microfluidic device that combines single-cell imaging and sequencing measurements to generate joint coordinates of protein-DNA interactions in both the physical space of the nucleus and the sequence space of the genome. I first applied this device to study nuclear organization in single cells, revealing which regions of the genome are associated with the nuclear lamina, and how this differs among cells of the same type and different types. In my future work, I plan to develop tools to map protein-DNA interactions in single meiotic cells and in the uncharted heterochromatic regions of the human genome.
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