Mass spectrometry, proteomics and their role in the pursuit of advancing scientific discovery.

Mass spectrometry is widely recognised as the most successful technology for understanding the proteome. Mass spectrometry, or MS, dates back to the late 19th century and one of the first MS instruments was constructed by Joseph John Thompson in 1912. This invention followed the Nobel Prize winning discovery of the electron determining its mass-to-charge ratio (m/z) in 1906. 

Unbeknown to most, there are many MS instruments in use today, ranging from airport security systems to applications used to understand the geology of planets. MS systems that are used for proteomics have four basic functions: 1) create ions, 2) separate the ions based on the mass and charge, 3) detect ions and determine their mass-to-charge (m/z) ratio and 4) select and fragment ions of interest. There are many types of mass analysers, such as Quadrupoles, Ion Traps, Orbitraps and Time of Flight instruments. 

Most scientists working in laboratories will have heard of Matrix-Assisted Laser Desorption/ Ionisation Time-of-Flight (MALDI-ToF) based mass spectrometry. This instrument is a crucial workhorse which gives us the mass in any uncomplicated sample. However, a cell produces many proteins in order to carry out its diverse functions. How can we begin to understand proteins in such a complex system? The answer to this challenging question is somewhat counter-intuitive; to break each protein into smaller peptide fragments and measure them, and in this way reconstitute the thousands of proteins present in the sample. This technique is called “bottom-up proteomics” or “shot-gun” proteomics.

In order to measure the peptide fragments, one needs to be able to isolate and fragment the many peptide ions. One of the key developments in MS based proteomics was the invention of the Orbitrap by Alexander Makarov in 2000 and its commercialisation by Thermo in 2005. This impressive piece of kit allows the simultaneous measurement of over thirty peptide fragments, and does this multiple times per second. Makarov was awarded the “ASMS Distinguished Contribution in Mass Spectrometry Award” in 2008 for this work. The continued advances in instrumentation have enabled the field of MS- based proteomics to come of age. 

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