The Chong Lab was awarded one of the CCE Chair's Council Innovation Awards this year with the project titled "A new method to decode the composition of biomolecular condensates in live human cells".
Known as the "dark matter of biology", intrinsically disordered protein regions (IDRs) are extremely abundant in the proteomes, play essential roles in numerous cellular processes, but lack well-defined protein structures and are therefore not amenable to conventional analysis. Recent discoveries that many IDRs can undergo multivalent interactions and form liquid-liquid phase separation (LLPS) condensates have opened an exciting new frontier for studying IDRs, but further dissecting how condensate formation leads to specific IDR functions has been hindered by a lack of methods to effectively determine the composition of LLPS condensates in the cell and thereby identify the LLPS-driving IDR's selective interaction partners. The central objective of the Innovation Grant project is to fill this gap by establishing the first method for determining the multivalent interaction partners of any IDR in its LLPS condensates in live human cells. Given the near-ubiquitous involvement of IDRs and biomolecular condensates in cell biology, the proposed method will provide a uniquely powerful tool for understanding numerous cellular processes and diseases and make a far-reaching impact in many biomedical fields.
Qinyu Han, a third-year chemistry graduate student in the Chong Lab, is leading this project. This work is also a collaborative effort with Tsui-Fen Chou and the Proteome Exploration Laboratory at Caltech.
The second 2024 CCE Innovation Award recipient was Rustem Ismagilov for "Exploring the chemistries that enable microbes to live in human tissues".
Microbes that live in human tissues, such as intestinal epithelia, overcome unique challenges: they must out-compete other microbes in a nutrient-rich environment, modify their surroundings, and evade immune response. The lab hypothesizes that such microbes have special mechanisms and make special molecules to enable colonization; however, studying the genomes of microbes associated with mammalian tissue has been difficult (or impossible) due to the high ratio of host to microbial DNA in such samples. Their newly published microbial enrichment method (MEM) breaks this bottleneck. MEM enables the construction of microbial metagenome assembled genomes from intestinal biopsies and other host-rich tissues. Ismagilov lab researchers are now using MEM technology to explore the microbial pathways and genes that enable microbes to live in human tissues.
The CCE Innovation Awards are granted by the CCE Chair's Council, which aims to provide seed funding for a new research direction that is not currently funded.