May 12, 2021 – MSDG Meeting

Abstract:  Trapped Ion Mobility on the timsTOF enables you to find more proteins, faster and with less sample than ever before with enhanced DDA and new DIA approaches using parallel accumulation and followed up with serial fragmentation (PASEF). Throughput is now primed for clinical research cohorts. New SpatialOMx workflows on the timsTOF fleX mean you can image molecules on a tissue section and run a deep coverage LC-MS/MS analysis from the same sample, and on the same instrument.

Abstract:  Transformative insights from a holistic approach at the systems level have great potential to elucidate disease mechanisms and to develop new therapeutic treatments for precision medicine. Proteomics is essential for deciphering how proteins interact as a system and for understanding the functions of cellular systems in human diseases. However, the unique characteristics of the human proteome, which include the large dynamic range of protein expression and the extreme complexity resulting from a plethora of post-translational modifications (PTMs) and sequence variations, make such analyses difficult. The top-down mass spectrometry (MS)-based proteomics, which is based on analysis of intact proteins, is arguably the most powerful method to comprehensively characterize proteoforms that arise from genetic variations, alternative splicing, and PTMs. My group has made significant advances in top-down MS for analysis of large intact proteins purified from complex biological samples including cell and tissue lysate as well as body fluids. Recently, we are employing a multi-pronged approach to address the challenges in top-down proteomics in a comprehensive manner by developing new MS-compatible surfactants for protein solubilization, novel materials and new strategies for multi-dimensional chromatography separation of proteins, novel nanomaterials for enrichment of low-abundance proteins, as well as a new comprehensive user-friendly software package, MASH Explorer for top-down proteomics. In this talk I will present our recent technology developments in top-down high-resolution mass spectrometry-based proteomics as well as its application to pharmaceutical research, cardiac systems biology and precision medicine.