The dynamics of gene expression, from the nucleus to mitochondria
Monday, September 12, 2022 - 4:15pm
Schultz 107
Quantitative & Computational Biology
LSI - Genomics


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Meeting ID: 942 9814 2648
Passcode: 554071

We are interested in the orchestration of gene expression processes across the cell. By studying genes encoded on both the nuclear and mitochondrial genome we seek to understand the many layers of regulation that underlie cellular processes in health and disease. In this talk, I will share two recent stories from my group. First, we have determined how mRNAs flow through the cell genome-wide by quantitatively measuring the rates at which RNAs are released from chromatin, exported from the nucleus, loaded onto polysomes, and degraded within the nucleus and cytoplasm. These rates varied substantially, yet transcripts from genes with related functions or targeted by the same transcription factors and RNA binding proteins flowed across subcellular compartments with similar kinetics. We used a machine learning model to identify additional molecular features that underlie the diverse life cycles of mammalian mRNAs. Second, we have resolved how the hundreds to thousands of copies of mitochondrial DNA are packaged into individual nucleoids without histones or other chromatin machinery important for nuclear genome compaction. We used long-read single-molecule accessibility mapping to resolve the compaction of individual full-length mitochondrial nucleoids at single-nucleotide resolution. We find that, unlike the nuclear genome, human mtDNA largely undergoes an all-or-none global compaction, with the majority of nucleoids existing in an inaccessible, inactive state. In addition, we demonstrate that the primary nucleoid-associated protein TFAM directly packages nucleoids via a ‘nucleation and spreading’ mechanism to coat mtDNA. Together, these findings reveal the primary architecture of mtDNA packaging and regulation in humans. 

Stirling Churchman

Stirling Churchman, Ph.D. is an Associate Professor in the Department of Genetics at Harvard Medical School. Dr. Churchman is particularly interested in how gene regulation is coordinated across the cell, from the nucleus to the mitochondria. Her lab developed native elongation transcript sequencing, NET-seq, that directly visualizes global transcriptional activity through mapping RNA polymerase density genome-wide with single-nucleotide resolution. Her group also discovered that cytosolic and mitochondrial translation programs are synchronized during mitochondrial biogenesis. A goal of the Churchman lab is to determine whether other layers of regulation are coordinated and the molecular mechanisms behind them.

Dr. Churchman majored in physics at Cornell University and obtained her doctorate in physics from Stanford University in 2008. She did her postdoctoral training with Jonathan Weissman at University of California, San Francisco. Dr. Churchman joined the Genetics Department at Harvard Medical School as an Assistant Professor in 2011. She is also an Associate Member of the Broad Institute of Harvard and MIT. Dr. Churchman has received a number of awards, including the Dale F. Frey Award for Breakthrough Scientists by the Damon Runyon Cancer Research Foundation, a Burroughs Wellcome Fund Career Award at the Scientific Interface and the Glenn Award for Research in Biological Mechanisms of Aging.

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