“B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) is the most common childhood cancer. Despite a good prognosis, two major clinical issues remain. Firstly, about 10% of children do not respond to standard treatment, making relapsed BCP-ALL the second largest cause of pediatric mortalities in the Western world. Secondly, current chemotherapy protocols (which last several years) are incredibly harsh, directly contributing to the global death toll and causing many long-term medical complications for survivors (spanning both physical and cognitive impairments).
Through several single-cell resolution analyses, we previously demonstrated that fuelled by parallel evolution and phenotypic convergence processes, a rare population of transcriptionally uniform – deeply quiescent – but genetically variegated cells escape induction chemotherapy (Turati et al., Nat. Cancer 2021). These data suggest that a better understanding of how cell quiescence in BCP-ALL is regulated, and impacted by chemotherapy, could help guide future efforts to improve and de-escalate treatment.
During the course of this project, you will probe proliferation/quiescence potential of individual BCP-ALL cells using a newly published functional cellular barcodes system called “Watermelon” which allows simultaneous tracing of individual cells’ lineage (clonal origin), proliferative history (quiescence potential), and global transcriptional state. Depending on the project length – and your specific research interest – you might learn one or more of the following: i) how maintain and expand BCP-ALL cells in vitro using an innovative induced pluripotent stem cells (IPS)-based BM organoid system, ii) how to generate and exploit a barcode library, and iii) how to identify and longitudinally track phenotypic changes in BCP-ALL cells exposed to treatment (via flow cytometry, microscopy and/or sequencing).
We are looking for a MSc (ideally over 20-week project) eager to learn the ropes of how wet lab works and interested in the biological questions and techniques highlighted above. Previous training/knowledge of cancer biology, as well as experience with cell culture and molecular biology are both desired but not required. The lab is located in the BMC A12 Molecular Haematology and Gene therapy unit.
If you have any questions you are welcome to email virginia.turati@med.lu.se“