PROJECT SUMMARY
We request funds for a novel mass spectrometer, the Orbitrap Astral, to be located at the Massachusetts General
Hospital (MGH) and to be used for proteomics studies focusing on cancer and Alzheimer’s disease research.
The proteome is defined as the entirety of all proteins in biological systems, and it encloses many different
aspects such as (i) protein expression and concentration, (ii) posttranslational protein modification such as
phosphorylation, acetylation, methylation, and ubiquitination, (iii) protein interactions, (iv) intracellular protein
localization, (v) enzyme activities, and many more. Most of this information can only be accessed through directly
measuring the proteome, and this is enabled through proteomics technology with mass spectrometry being the
most important tool. Nevertheless, proteomics usage is small when compared to the wide usage of genomics
technologies, and we believe this hinders progress in a better understanding of complex diseases such as cancer
and neurodegenerative disorders and ultimately a better treatment of these diseases. So why is proteomics not
more broadly used in disease research and has not been incorporated into the diagnostics in clinical treatment?
We believe two major reasons are a lack of sensitivity when compared to genomics technologies and a lack of
sample throughput, which impacts studying complex diseases and results in high costs of proteome analysis.
Both hurdles were addressed by the development of a novel mass spectrometer by Thermo Fisher
Scientific, the Orbitrap Astral, which includes a new extremely fast mass analyzer with unprecedented sensitivity.
This high-resolution accurate-mass (HRAM) analyzer enables extreme scan rates (200 Hz) at single ion
detection limits and provides unprecedented performance across all current mass spectrometry-based
proteomics approaches including isobaric labeling-based multiplexed quantification and data-independent
acquisition (DIA). First data generated with the instrument show that the Orbitrap Astral is a game changer for
proteomics that will redefine what can be achieved in the field. It outperforms existing mass spectrometers by
several folds in mapping cell line and tissue proteomes, plasma proteomes, phosphoproteomes, and proteomes
of low sample inputs (single-cell proteomics).
The instrument will benefit the research of 13 projects (9 major and 4 minor users) in cancer and
Alzheimer’s disease research and will be available to NIH-funded researchers beyond the MGH in Boston and
nationwide. It will be supported by all levels of institutional levels, including the MGH Cancer Center, and the
MGH Executive Committee for Research. Institutional funds are committed to installing, maintaining, and
running the platform. We believe that the Orbitrap Astral will drive new discoveries in cancer and Alzheimer’s
research and beyond including the identification of disease biomarkers for detection and monitoring progress,
for identifying cancer vulnerabilities including combination treatment targets for overcoming treatment resistance,
and as a platform to develop even faster and deeper methods for exploring disease proteomes.