PhD defense on January 11, 2013
Christian Kelstrup will defend his PhD Thesis: Challenges in Proteomics - Applications and developments
Location: Adolph Hannover Auditorium at Panum
Faculty Of Health Sciences, University of Copenhagen, Blegdamsvej 3B,
DK-2200 Copenhagen N
How to get there: Map
Proteins are at the center of biology and medicine. Tools to study these have therefore always been in high demand. In the last decade, one such technology has seen tremendous developments and has changed how many proteins we can measure at once. This technology holds the promise to quantify the entire proteome and is therefore termed quantitative proteomics. The technology is based on liquid chromatography coupled to tandem mass spectrometry and subsequently relies heavily on bioinformatics for interpretation. Being technologically focused, this thesis seeks to address two central questions: How can this technology be applied to provide answers to important questions in biology? And how can this technology be improved to give better and more precise answers?
In order to put the work performed into proper perspective, a critical description of the core technological workflow is explored. This serves to highlight the incomplete nature of the technology and how much it can still improve. Yet it is already powerful as shown by application of the technology through collaborations in two different cell signaling areas of biology. The first application is a global analysis of the yeast osmotic stress response, where known players are validated and novel ones suggested. In the second approach, the biased signaling of a seven trans-membrane receptors is measured and reveals a previously unappreciated diversity and quantity of signaling. In the last part of the thesis, technological improvements are described. One paper is an investigation of how gas-phase phosphate group transfer during fragmentation affects the bioinformatics interpretation. It is investigated how the bioinformatics workflow can be improved and a novel fragment ion is shown to be usable for site localization. A second technological paper attempts to improve the mass spectrometric acquisition methods on a new machine. In total, this thesis describes the successful application of the powerful proteomic technology yet tries to frame this in a context of new possibilities for technological improvements.