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Development of novel affinity enrichment strategies for clinical applications using selected reaction monitoring

Time: Fri 2022-10-14 10.00

Location: Gradängsalen, Teknikringen 1, Stockholm

Language: English

Subject area: Biotechnology

Doctoral student: Andreas Hober , Proteinvetenskap, Science for Life Laboratory, SciLifeLab

Opponent: Professor Johan Malmström, Division of Infection Medicine, Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden

Supervisor: Professor Mathias Uhlén, Science for Life Laboratory, SciLifeLab, Proteinvetenskap; Docent Fredrik Edfors, Proteinvetenskap, Science for Life Laboratory, SciLifeLab; Doctor Björn Forsström, Science for Life Laboratory, SciLifeLab, Proteinvetenskap, Atlas Antibodies AB, Bromma, Sweden

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QC 2022-09-20

Abstract

Proteins are key components of any living organism and an essential part of life itself. They can provide cells with structure and perform life-sustaining intracellular reactions. As organisms grow more complex, this task expands even further. The proteins’ areas of responsibility suddenly also include communication and coordination between cells and throughout entire organisms, such as the human body. Everything that can be touched and felt on a living organism is composed of millions and millions of proteins tightly packed together. They are even the molecules responsible for propagating the signals that make up the sense of feeling. Understanding the role of proteins in the complex system of life is essential for understanding what makes up a healthy human and what causes disease. This knowledge makes up the foundation of modern medicine, and to further this knowledge, allowing for new treatments and preventative interventions, the study of proteins is crucial. The large-scale study of proteins, proteomics, is an extensive field of research where a vast toolbox of technologies has been implemented. The foundation for this toolbox is made up of mass spectrometry- and affinity-based technologies.

In this thesis, both mass spectrometry-based proteomics and affinity-based proteomics will be explored. The first part, Paper I and Paper II, describe the use of selected reaction monitoring for measuring proteins of clinical relevance in human blood plasma. The second part, Paper III and Paper IV, highlight the importance of validating reagents used for affinity-based proteomics and how this can be achieved in a high throughput manner. Lastly, Paper V showcases how a combined strategy, relying on both affinity-based proteomics and mass spectrometry-based proteomics, can capitalize on the best properties of each technology and how this combined strategy can even be utilized for diagnostic purposes.

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