Dan Bracha, PhD, Assistant Professor

Deciphering and Reprogramming Subcellular Self-Organization:
We are a multidisciplinary group studying the self-organization and modes of functions of dynamic clusters of biomolecules and their role in cellular health and disease. We develop and utilize controllable intracellular tools for probing and manipulating the collective activities of biomolecules, leveraging fundamental insights into novel therapeutic strategies and cutting-edge synthetic biology applications.

Our research aims to enhance our understanding of the collective properties and function of dense biomolecular phases and their role in cellular health and disease. We are particularly intrigued by a group of conformationally unstable proteins, known as intrinsically disordered proteins (IDPs), that possess a remarkable ability to phase-separate into intracellular liquid bodies. These physicochemical entities are programmed to generate intracellular order and to locally orchestrate complicated, multi-component cellular tasks, ranging from gene regulation and genome organization to cellular signaling, stress response, and assembly of ribonucleoprotein complexes. However, the driving forces underlying the biogenesis of these phase-separated structures and the collective modes of function of their building blocks are poorly understood. Moreover, the beneficial ability of disordered proteins to phase separate also harbors a grave risk and is associated with enhanced aggregation propensity implicated in the pathogenesis of devastating diseases, including various neurodegenerative disorders and cancers. Studying these dynamic structures and elucidating the link between their physicochemical nature, function, and dysfunction poses a major challenge for conventional molecular biology and biophysical technologies.