Michael Group

Genome Regulation and Biological Timekeeping

Circadian rhythms are universal biological phenomena in various life forms, from single-cell green algae to humans. These rhythms are tightly linked to the daily light-dark cycle and synchronize physiology and behavior with the solar day. They serve as an evolutionary adaptation, allowing organisms to anticipate and adjust to daily environmental changes. In mammals, the disruption of circadian rhythms, whether caused by external influences or genetic factors, can lead to numerous diseases, including diabetes, cardiovascular issues, premature aging, and cancer. Notably, nearly every cell in the human body possesses an internal molecular clock, orchestrating integrated biochemical processes on a roughly 24-hour cycle. The molecular clockwork coordinates nuclear processes such as the three-dimensional (3D) organization of DNA, transcription, and ribosome biogenesis to achieve its extensive influence, giving rise to a daily peak in gene activity.

The Chromatin Structure and Rhythms lab aims to decipher how the spatial organization of genes and macromolecular assemblies within the nucleus contributes to precise and environmentally sensitive gene control. We are particularly interested in investigating how transcription factors and their cofactors interact with chromatin, a dynamic structure formed by DNA and histone proteins, to control gene activity. We employ diverse techniques such as biochemistry, chemical biology, and genomics to uncover how the interplay between transcription factors and the histone code – the chemical tags on chromatin – influences gene regulation. We also use cutting-edge imaging techniques like cryo-electron microscopy (cryo-EM), including single-particle and tomography approaches, to elucidate the ultrastructure of chromatin and its regulatory complexes within cells. By utilizing the circadian system as a model in diverse organisms, including human cells and green algae, we seek to unravel fundamental principles of gene regulation across multiple biological scales and gain insights into how cells keep time.