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Project

High-troughput mapping of melanoma cell states and transitions using pooled CRISPR screening with single-cell readout

Our objective is to achieve the ambitious goal of delineating the gene regulatory networks of each melanoma cell state, and its transcription factors and chromatin modifiers and of the dynamic transitions between them, we will perform a systematic screen of hundreds of human TFs and co-factors. Therefore, we will use single-cell CRISPR screens that allow perturbing TFs and chromatin regulators using CRISPR guide RNAs, while simultaneaously determining teh transcriptome or epigonome of single-cells.

Our specific aims are:

1 A CRISPR screen with single-cell transcriptome readout (CROP-seq), applied to a panel of TFs and chromatin modifiers of cell states and transitions

2 A CRISPR screen with single-cell epigenome readout applied to the same panels of TFs and chromatin modifiers. This aim also includes follow-up validation.

3 Blocking of specific clinically-relevant cell states and transitions, after prioritization, using epigenetic drugs targeting transcriptional co-factors and chromatin modifiers.

 

Date:1 Oct 2019 →  18 Mar 2022
Keywords:CRISPR screen with single-cell transcriptome readout, CRISPR screen with single-cell epigenome readout, epigenetic drugs targeting transcriptional co-factors and chromatin modifiers
Disciplines:Cancer therapy, Bio-informatics and computational biology not elsewhere classified