Combining CRISPR screening and single-cell RNA sequencing to unravel the mechanisms of T-cell acute lymphoblastic leukemia

In this project we aim to use a CRISPR/Cas9 inactivation screen of 83 genes that are recurrently inactivated in T-cell acute lymphoblastic leukemia (T-ALL). We will perform the screen in combination with single-cell RNA-sequencing, so that we can use the effect on gene expression as a read-out for the screen.

In the first part, we will investigate the impact of single gene perturbations on the cellular processes and aim to characterize the similarities and differences between the different perturbations.

Secondly, we will study how multiple genes cooperate in the development of T-ALL. We will assess how the inactivation of the 83 potential tumor suppressor genes affects the gene expression profiles driven by major oncogenic transcription factors in T-ALL. Furthermore, we will also study how multiple gene perturbations affect the cellular processes.