Lucas Jae - Functional Genomics

Virtually every form of human disease is shaped by the individual or concerted action of genes. Incredibly successful work in model organisms – most importantly in yeast – has paved the way to build genetic wiring diagrams of the eukaryotic cell (for a recent example see Costanzo et al., Science, 2016). Mapping genetic interactions through knock-out genetics is not only a remarkably useful tool in the mechanistic dissection of complex cellular phenomena, but can also aid the annotation of orphan genes and potentially reveal new strategies to therapeutically combat disease states. However, strategies for comparable experiments in a human system have long been hindered by the diploid nature of the human genome, which buffers against individual genetic insults. With the advent of haploid mutagenesis in human cells (Carette et al., Science, 2009) and repurposing of CRISPR-Cas (Jinek et al., Science, 2012) we can finally embark on similar genetic expeditions in the human system. 

Examples of genetic interactions. Adapted from van Leeuwen*, Pons* et al., Science 2016.

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