This project aims to capture the heterogeneity of acute lymphoblastic leukemia (ALL) MRD, and identify characteristics of ALL MRD during chemotherapy treatment. The researcher will identify and characterize residual patient ALL cells during chemotherapy treatment by single cell multiomics.
ALL MRD will be generated by sorting residual ALL MRD cells from ALL patient samples and by expanding those cells by injection into immune-deficient mice. Subsequently, MRD ALL cells will be characterized by combined scRNA, scATAC sequencing using the 10X Genomics single cell multiome sequencing approach, combined with protein profiling using TotalSeq antibodies, and by Mission Bio Tapestry.
Next, in vivo CRISPR drop out screens with selected small gRNA libraries to identify genes/pathways that upon knockdown will result in reduced survival of ALL MRD will be performed, which will indicate which genes are essential for the development of ALL MRD.
Finally, as a complementary approach, the researcher will in collaboration with DC6 test interventions targeting the identified genes/pathways using the “evolutionary trap approach” for reduced survival of ALL MRD cells.
Host:
VIB-KU Leuven Center for Cancer Biology, Leuven, Belgium.
Supervisor:
Prof. Jan Cools
Duration:
48 months, starting 1-5-2025
Profile doctoral candidate:
Master’s degree in life sciences, other (bio)medical sciences, or related, and practical experience in cell biology, molecular biology, and basic bioinformatics.
In addition:
The researcher will be embedded in the team of Jan Cools at VIB-KU Leuven Center for Cancer Biology, and will intern at Czech University (3 months, Czech Republic, supervisor Jan Stuchly) to have additional bioinformatic training, and at INSERM (Paris, France, 3 months, supervisors Alexandre Puissant/Raphael Itzykson) to identify evolutionary traps using various drugs.