Utrecht University & Bruker Announce Collaboration to Develop Methods for Studying Protein Structures & Interactions by Mass ...
August 07 2020 - 7:00AM
Business Wire
Crosslinking Mass Spectrometry (XL-MS) Now
Can Leverage the PhoX Crosslinker and TIMS/PASEF Methods with the
Large-Scale Use of Accurate Collision Cross Sections (CCS)
Bruker Corporation (Nasdaq: BRKR) today announced a
collaboration with Utrecht University to advance the study of the
3-D structures and interactions of proteins by mass spectrometry.
The laboratory of Albert Heck at Utrecht University has been a
leader in proteomics and the study of protein structure and
interactions by mass spectrometry for over two decades. Richard
Scheltema recently joined Utrecht University as group leader to
focus on crosslinking mass spectrometry (XL-MS) for structural and
interaction proteomics.
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Albert Heck, Utrecht University (Photo:
Business Wire)
The collaborative work will focus on the development of TIMS
(Trapped Ion Mobility Spectrometry) and PASEF (Parallel
Accumulation Serial Fragmentation) methods, along with crosslinkers
and XL-MS software for the timsTOF Pro 4D-Proteomics mass
spectrometer, in order to take advantage of its unique large-scale,
accurate CCS workflows. These have been described in the
foundational paper “Benefits of Collisional Cross Section Assisted
Precursor Selection (caps-PASEF) for Cross-linking Mass
Spectrometry “, just published in a breakthrough paper in Molecular
and Cellular Proteomics.1
Bruker plans to commercialize the results of the collaboration
as integrated solutions for the study of protein structures and
interactions using XL-MS. Combining the novel, enrichable PhoX
crosslinker2, developed by Heck and Scheltema, with the extreme
speed and sensitivity of PASEF methods on the timsTOF Pro
platform, enables the discovery of more crosslinked products which
yield more information about protein structures and interactions.
Advanced analysis software is key, as XL-MS data is more complex
and even more information-rich than typical shot-gun proteomics
experiments. Scheltema is working on enabling the innovative XlinkX
software to process TIMS/PASEF data and making it available to the
community of timsTOF Pro users.
Albert Heck of Utrecht University commented: “We are delighted
to work with Bruker on the further development of workflows for
XL-MS that take advantage of the speed of PASEF and the unique
large-scale, accurate CCS data to enhance the detection of
crosslinks in XL-MS. We are excited by the initial results
published in Molecular and Cellular Proteomics and look forward to
advancing XL-MS even further. We are also interested in other
applications of ion mobility separation and CCS on the timsTOF Pro
to glycoproteomics and top-down proteomics.”
Dr. Gary Kruppa, the Vice President of Proteomics at Bruker,
said: “Having personally been involved in some of the conceptual
work in XL-MS in 2001 at Sandia National Laboratory, I believe the
advances made by Heck’s group will make this technique more
routinely available for structural biology studies using the
timsTOF Pro. Our collaboration with Utrecht University will
accelerate adoption of XL-MS within the broader structural and
interaction proteomics community.”
Richard Scheltema of Utrecht University stated: “My group
intends to push the boundaries of PASEF to enhance XL-MS workflows
by making them CCS-aware. We have a significant ongoing effort in
bioinformatics applied to analyzing XL-MS data using our XlinkX
software.3,4 We are excited to work with the open data-format
architecture of the timsTOF Pro in XlinkX to develop code that can
use large-scale, accurate CCS values for the identification of
crosslinks and to further improve false discovery rate (FDR)
calculations.”
- Benefits of Collisional Cross Section Assisted Precursor
Selection (caps-PASEF) for Cross-linking Mass Spectrometry.
Steigenberger B, van den Toorn H, Bijl E, Greisch JF, Räther O,
Lubeck M, Pieters RJ, Heck AJR, Scheltema RA., Mol Cell Proteomics,
2020 Jul 21:mcp.RA120.002094. doi: 10.1074/mcp.RA120.002094. Online
ahead of print.
- PhoX: An IMAC-Enrichable Cross-Linking Reagent. Steigenberger
B, Pieters RJ, Heck AJR, Scheltema RA. ACS Cent Sci. 2019 Sep
25;5(9):1514-1522.
- Proteome-wide profiling of protein assemblies by cross-linking
mass spectrometry. Liu F, Rijkers DT, Post H, Heck AJ. Nat Methods.
2015 Dec 12(12):1179-84. doi: 10.1038/nmeth.3603
- Klykov, O., Steigenberger, B., Pektaş, S. et al. Efficient and
robust proteome-wide approaches for cross-linking mass
spectrometry. Nat Protoc 2018 Dec 13, 2964–2990.
https://doi.org/10.1038/s41596-018-0074-x
About Bruker Corporation (Nasdaq: BRKR)
Bruker is enabling scientists to make breakthrough discoveries
and develop new applications that improve the quality of human
life. Bruker’s high-performance scientific instruments and
high-value analytical and diagnostic solutions enable scientists to
explore life and materials at molecular, cellular and microscopic
levels. In close cooperation with our customers, Bruker is enabling
innovation, improved productivity and customer success in life
science molecular research, in applied and pharma applications, in
microscopy and nanoanalysis, and in industrial applications, as
well as in cell biology, preclinical imaging, clinical phenomics
and proteomics research and clinical microbiology.
About the Heck-lab & Scheltema-lab at Utrecht
University
The research groups of Albert Heck and Richard Scheltema are
embedded in the Science Faculty of Utrecht University (NL). A large
emphasis of the group is on the development and applications of
advanced mass spectrometry-based proteomics technologies.
Complementary to the proteomics efforts, the group is also
well-known for its expertise in mass spectrometry based structural
biology, pioneering methods in native mass spectrometry and
cross-linking mass spectrometry. The group coordinates the European
Proteomics Research Infrastructure (EPIC-XS, link epic-xs.eu) and
heads the proteomics core in the Dutch X-Omics Initiative
(www.x-omics.nl).
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