Decoding cellular circuits to identify therapeutic targets

Employing the Cell-seq technology, the Brummelkamp laboratory (inventor of Cell-seq) and Scenic Biotech BV (exclusive license holder of Cell-seq) have already established Phenosaurus, a database containing about 100 haploid screens. Each screen reveals whether the inactivation of a particular gene results in changes in expression or activity status of a specific protein. As the latter are the workhorses of the cell, playing important roles in cellular processes such as repairing DNA damage or cell division, Phenosaurus contains millions of links between genes and cellular processes. In this project the Brummelkamp laboratory, Scenic Biotech BV and the Wessels laboratory will further expand Phenosaurus and employ it to perform advanced computational analyses to reconstruct the cellular circuits that describe how genes control cellular processes.

Societal and economic impact: A more complete understanding of the cellular circuits that control  important processes in the cell will reveal ways in which we can safely interfere therapeutically in  abnormal processes, with the aim to rebalance disease. More than 7,000 distinct types of rare disease  exist and 80% of the rare diseases are caused by genes that do not function well. Only 5% of rare diseases  have an FDA approved treatment. In 2018 drug sales for rare disease are expected to reach 138  billion US dollar, and they are predicted to reach 21.7% in global prescription sales by 2024. 

Envisioned end results: By the end of the projecta much more complete map will be established of cellular circuitry representing which cellular processes a gene controls and the mechanisms through which such control is affected. This will be a rich resource to identify new drug targets for diseases and promising targets will be pursued by Scenic Biotech BV.