Karissa Sanbonmatsu
Structural Biologist at Los Alamos National Laboratory.
Science for the next pandemic: from large-scale simulations of genes to 3-D reconstructions of chromosomes
December 9, 2020 - 12:00 PM Eastern Time
Talk Abstract:
Talk Abstract: While most cells in the body have identical 1-D genomes, cells in different tissues have remarkably different cell shapes, internal structures and functionality. Recent studies suggest that the 3-D structure of the genome differs from cell to cell, and that these differences have profound effects on the function of the underlying DNA, impacting cell structure and functionality. Interestingly, viral infections also affect the 3-D organization of the genome. While the common paradigm suggests that chromosome compaction causes gene silencing, few mechanistic studies on full chromosomes have been performed to support this. Recently, the development of high throughput sequencing technology has produced precise information regarding gene-gene interactions. The Hi-C technique cross links chromosomes with themselves, revealing DNA-DNA interactions. These samples are then fragmented and ligated to produce small loops containing the DNA-to-DNA interaction sequences. Finally, a 2-D contact map is produced. While many suspect that patterns in the 2-D contact map reflect 3-D proximity of genes, this is difficult to discern. We use constrained molecular simulations to produce 3-D reconstructions of full chromosomes highly consistent with Hi-C experimental data for the process of X chromosome silencing, shedding light on the chromosome compaction. Changes in 3-D structure, could, in principle, be used to detect more subtle signatures of viral infections. In addition to full chromosome simulations, results from the first explicit solvent MD simulations of an entire gene locus (using the LANL Trinity supercomputer) will be presented. This pilot study is the first billion-atom simulation published in the biosciences. Simulations such as these have the ability to push HPC resources much more than conventional simulations in the physical sciences.
Speaker Bio:
Dr. Karissa Y. Sanbonmatsu is a structural biologist at Los Alamos National Laboratory, where she leads the Sanbonmatsu Laboratory established in 2001. Her team uses computational and experimental approaches to understand the mechanism of a diverse array of epigenetic and non-coding RNA systems, including chromatin, ribosomes, riboswitches and long non-coding RNAs.
She has been a leading figure in structural studies of long non-coding RNAs in epigenetics and is currently studying the mechanism of epigenetic effects involving chromatin architecture. Her body of work led her to be elected as a Fellow of the American Physical Society in 2012. Most recently, her group set the record for the world’s largest published biomolecular simulation at one billion atoms, the first simulation of an entire gene.
She described her work with epigenetics and came out as transgender in a 2014 TEDxTalk. She also delivered a TED talk at TEDWomen on The biology of gender, from DNA to the brain, in November 2018. The talk, with over 2 million views, covers epigenetics and how hormones control DNA decisions during embryo development.