Method Development
Developing new mass spectrometry methods
We develop mass spectrometric methods and technologies that improve the sensitivity, resolution, accuracy, and speed of proteomic experiments. Our contributions include Multidimensional Protein Identification Technology (MudPIT) and data-independent acquisition (DIA), which enable deep proteome coverage of complex biological samples.
- ›Multidimensional Protein Identification Technology (MudPIT)
- ›Data-Independent Acquisition (DIA) workflows
- ›Novel ionization and fragmentation strategies
- ›Ultrafast chromatography coupling
Bioinformatics & Software
Software for analyzing proteomics data
We develop computational tools and algorithms for analyzing large-scale MS-based proteomics datasets. From the SEQUEST database search algorithm to DTASelect and Census, our software is used by proteomics labs worldwide to identify and quantify proteins from complex mixtures.
- ›SEQUEST algorithm for peptide-spectrum matching
- ›DTASelect for protein-level filtering
- ›Census for isotope-based quantification
- ›Integrated Proteomics Pipeline (IP2)
Post-Translational Modifications
Characterizing protein modifications
We employ targeted and global proteomics approaches to characterize post-translational modifications (PTMs) including phosphorylation, ubiquitination, acetylation, and glycosylation. Understanding these modifications is central to how cells signal and how disease develops.
- ›Global phosphoproteomics workflows
- ›Ubiquitin site mapping
- ›Glycoproteomics and glycosite quantification
- ›Acetylation and metabolic labeling
Disease Biology
Proteomics applied to human health
We apply our proteomics toolkit to understand the molecular basis of human disease. Current projects include studies on cystic fibrosis, schizophrenia, HIV, SARS-CoV-2, and neurodegenerative conditions. Proteomics allows us to measure the impact of drugs and identify new therapeutic targets.
- ›Cystic fibrosis CFTR interaction networks
- ›Schizophrenia brain proteomics
- ›Viral proteomics (HIV, SARS-CoV-2)
- ›Drug target identification
Protein-Protein Interactions
Mapping the cellular interactome
We use affinity purification–mass spectrometry (AP-MS) and cross-linking MS strategies to map protein-protein interactions and characterize multi-protein complexes. This work reveals how proteins function together in cellular machines and signaling networks.
- ›Affinity purification–mass spectrometry (AP-MS)
- ›Chemical cross-linking MS (XL-MS)
- ›Protein complex stoichiometry
- ›Structural proteomics
Structural Proteomics
Protein structure and dynamics by mass spectrometry
By combining hydrogen-deuterium exchange (HDX-MS), cross-linking MS, and native MS, we probe protein conformation, dynamics, and interactions at the proteome scale. These approaches complement cryo-EM and X-ray crystallography.
- ›Hydrogen-deuterium exchange (HDX-MS)
- ›Native mass spectrometry
- ›Protein conformational dynamics
- ›Integrative structural biology
Our Approach
Research in the Yates lab is focused on the development and application of mass spectrometry-based proteomics techniques to a wide range of biological questions. The lab has helped shape the field, developing methods that are now in common use.
Our three areas of work (bioinformatics and software, methods development, and biological applications) work together to study complex biological systems.