Chemical Biology of Protein Aggregation
 

The Zhang lab works at the intersection between chemistry and biology. Many important biological questions cannot be fully addressed due to the lack of proper methodologies. The lab aspires to tackle these questions by developing and applying novel chemical tools.
 
The main focus is protein misfolding and aggregation that occur in stressed cells with deficient proteostasis. These molecular events have been associated with a variety of diseases that are termed as protein misfolding diseases. Protein aggregation is a multiple step process that involves misfolded soluble and insoluble aggregates. It is unclear which of these conformations could lead to cytotoxicity that is associated with diseases. To tackle this question, the lab develops innovative chemical methodologies that allow the community to visualize and differentiate, in live cells and organisms, the many conformations through the process of protein aggregation. It combines expertise from synthetic chemistry, in vitro biochemistry and cell biology. The ultimate goal is not only to provide a tool set for the community, but also to define (in live cells) biochemical nature of species in protein aggregation and their mechanism of action in disease initiation and progression.
 
Currently, the Zhang lab attempts to address the following questions:
 
1)    How can the lab detect and differentiate various conformational species during protein aggregation in live cells and organisms?
 
2)    How can it quantify proteostasis deficiency during cellular stress?
 
3)    How can the lab detect and understand misfolding and aggregation of intrinsically-disordered proteins, represented by a class of RNA-binding proteins (RBPs) that harbor prion-like domains, in membrane-less organelles?
 
4)    How can it develop small molecules that could prevent misfolding and aggregation, if any, of RBPs in membrane-less organelles?

Source:  https://www.zhanglab.chem.psu.edu/