Fawzi Laboratory at Brown University
The work in the group centers on determining the structure, dynamics, and molecular interactions of large assemblies of intrinsically disordered proteins. In particular, we focus on 1) liquid-liquid phase separated forms of RNA-binding proteins associated with inclusion formation in amyotrophic lateral sclerosis (ALS / Lou Gehrig's disease) and frontotemporal dementia and 2) protein aggregates implicated in Alzheimer’s Disease. Using a combination of novel NMR spectroscopy approaches and atomistic simulation supplemented by biophysical and imaging methods, we determine high-resolution structures of these species and their toxic interactions with other macromolecules and membranes, as well as their interactions with potential therapeutic agents. The tools that we are developing are uniquely tailored to observe the detailed structure and interactions of these assemblies whose disordered and transient nature make them difficult to observe by classic structural techniques, making our methods broadly applicable to other unanswered questions in biology. Research projects for new students are available both in the expression and purification of new protein targets as well as NMR spectroscopy of aggregation-prone proteins already in hand. The group has shared access to 500 MHz and 850 MHz Bruker NMR spectrometers equipped with cryogenic probes maintained by the Brown Structural Biology Core Facility.