Understanding molecular mechanisms at the intersection of chromatin & transcription
The Farnung Lab answers key mechanistic questions at the intersection of chromatin, transcription, and replication. We employ biochemical, biophysical, machine learning, and structural biology approaches to understand how the transcription machinery, histone modifying enzymes, chromatin remodelers, and the nucleosome interact to regulate gene expression. In parallel, we investigate how epigenetic information is retained during DNA replication.
Elucidating transcription through chromatin with visual biochemistry
Our research combines state-of-the-art biochemistry and cutting-edge single-particle cryo-electron microscopy to generate molecular movies depicting the transcription machinery traversing its native chromatin templates. Our work uncovers how chromatin organization is maintained and epigenetic information preserved.
Dissecting genome duplication in a chromatin context
We investigate how the eukaryotic replisome navigates nucleosomal templates during genome duplication. Using in vitro reconstitution, in silico structure prediction, and pseudo-time resolved cryo-EM approaches, we visualize replication intermediates at near-atomic resolution. These structures uncover the molecular strategies by which the DNA replication machinery engage and retain nucleosomes to achieve epigenetic inheritance.
Unraveling the function of chromatin remodelers
ATP-dependent chromatin remodelers play an important role in maintaining genome organization and providing accessibility to genomic information. We aim to better understand how chromatin remodelers are recruited to specific genomic loci to shape cell fate decisions, embryonic development, and cell homeostasis. To do so, the Farnung lab employs biophysical methods and structural biology approaches. Our work provides important insights into how chromatin remodelers contribute to the emergence of a broad range of cancers and neurodevelopment disorders.