Collection From Molecules and Cells to Human Health : Ideas and concepts
Organizer(s)
Date(s)
27/04/2024
The proteome in context
The question how genetic variability is translated into phenotypes is fundamental in biology and medicine. Powerful genomic technologies now determine genetic variability at a genomic level and at unprecedented speed, accuracy and (low) cost. Concurrently, life style monitoring devices and improved clinical diagnostic and imaging technologies generate an even larger amount of phenotypic information. However, the molecular mechanisms that translate genotypic variability into phenotypes are poorly understoodand it has been challenging to generally make phenotypic predictions from genomic information alone. The generation of a general model or theory that makes accurate predictions of the effects of genotypic variability on a cell or organism seems out of reach, at least for the intermediate future. We therefore propose that the precise measurement of molecular patterns that best reflect the functional response of cells to (genomic) perturbations would have great scientific significance. We define the term “proteotype” as a particular instance of a proteome in terms of its protein composition and organization of proteins into functional modules. In the presentation we will discuss recent advances in SWATH/DIA mass spectrometry that support the fast, accurate and reproducible measurement of proteotypes. We will show with specific case studies that i) the proteotype is highly modular, ii) genotypic changes cause complex proteotype changes and iii) that altered proteotypes affect phenotypes. Overall, the presentation will introduce the proteotype as a close indicator of the biochemical state of a cell that reflects the response of the cell to (genomic) perturbation and is strong determinant of phenotypes.
