Publications

Cellular reprogramming drives cells from one stable identity to a new cell fate. By generating a diversity of previously inaccessible cell types from diverse genetic backgrounds, cellular reprogramming is rapidly transforming how we study disease. However, low efficiency and limited maturity have limited the adoption of in vitro-derived cellular models. To overcome these limitations and improve mechanistic understanding of cellular reprogramming, a host of synthetic biology tools have been deployed. Recent synthetic biology approaches have advanced reprogramming by tackling three significant challenges to reprogramming: delivery of reprogramming factors, epigenetic roadblocks, and latent donor identity. In addition, emerging insight from the molecular systems biology of reprogramming reveal how systems-level drivers of reprogramming can be harnessed to further advance reprogramming technologies. Furthermore, recently developed synthetic biology tools offer new modes for engineering cell fate.

Connecting the molecular structure and function of chromatin across length and timescales remains a grand challenge to understanding and engineering cellular behaviors. Across five orders of magnitude, dynamic processes constantly reshape chromatin structures, driving spaciotemporal patterns of gene expression and cell fate. Through the interplay of structure and function, the genome operates as a highly dynamic feedback control system. Recent experimental techniques have provided increasingly detailed data that revise and augment the relatively static, hierarchical view of genomic architecture with an understanding of how dynamic processes drive organization. Here, we review how novel technologies from sequencing, imaging, and synthetic biology refine our understanding of chromatin structure and function and enable chromatin engineering. Finally, we discuss opportunities to use these tools to enhance understanding of the dynamic interrelationship of chromatin structure and function.