Final Report Summary - PROTEINSEQ (Sensitive, specific high-throughput plasma proteome analysis via ProteinSeq) According to Sydney Brenner “Progress in science depends on new techniques, new discoveries and new ideas, probably in that order”. Work in my lab takes a firm aim at developing molecular techniques that shed light on new mechanisms in biology and pathology. My ERC project has aimed to enable high-performance, high-throughput molecular assays, mainly at the level of proteins, in research and later for medical diagnostics. The proximity ligation or extension protein assays developed in my lab and then in our spin-out Olink now permit high throughput high-performance protein assays of large sets of proteins in large numbers of patient samples. We have greatly improved assay performance and demonstrated the ability to use sample collections in the form of blood spots dried on paper for extensive biobanking, and we have used the assays to search for biomarkers in a number of diseases. An intriguing class of biomarkers that has been in focus is exosomes or microvesicles, released from cells and potentially reporting damage to specific organs. Our proximity techniques have been applied to enable distinction and counting of individual exosomes according to their protein compositions. Because of the broad repertoire of proximity assays established by Olink my lab has settled for a lower number of protein assays than originally intended, and instead our focus has been on increasing overall assay performance and throughput, for example by enabling further increase of sensitivity on par with the best technologies currently available, and improving reagent functionalization to expand repertoires of markers. We have demonstrated that also low molecular weight drugs serve as affinity reagents in proximity assays, and we have adapted assays for high-throughput analysis of histological markers. The project has also allowed us to explore a number of new molecular technologies for improved molecular analysis at levels of proteins and nucleic acids, resulting in six new patent applications. We have also very actively disseminated our technologies not only through publications but also through technology service facilities and via spin-outs and licensees.
