The YRC is currently focused on developing new technologies to make controlled perturbations within the cell and then to test the effects of these perturbations on pathway activity, protein level and protein structure. To accomplish this, technology development in the YRC is grouped into three broad areas: perturbing and sensing changes to complex pathways, detection and quantitation of proteins by mass spectrometry, and higher-order protein structure.
Perturbing and Sensing Changes to Complex Pathways
The YRC is developing novel genome engineering approaches, selection systems, methods to disrupt protein-protein interactions, and biosensors. These efforts will allow us to make both large-scale and targeted changes to cells, to identify among the cells that have been changed those with useful properties, and to detect the level of expression of either a ligand or a protein in cells that have been engineered.
Detection and Quantitation of Proteins by Mass Spectrometry
The YRC is working to improve the depth, throughput, and scope of traditional mass-spectrometry based proteomics experiments by developing new technology for the detection and quantitation of proteins across many samples. This includes data independent acquisition (DIA) technology, enrichment strategies for very low abundance proteins, analysis of intact proteins, and molecular painting.
The YRC is developing novel techniques to determine the structure of proteins and protein complexes. We are developing new techniques using cross-linking, molecular painting, and co-evolution that complement current methods of structural determination and enable researchers to address structural questions that were previously out of reach.