Investigating the role of chromatin accessibility in the global transcription regulation in Leishmania quiescent cellusing multiomic single cell approaches (LEISHCHROMAQ)

Quiescence is a physiological state allowing micro-organisms to survive many environmental insults and is characterized by a reversible cell division arrest and metabolic downregulation. It is essential for the perpetuation of pathogen populations, contributes to the success of parasitism and might explain several (sub-)clinical features like asymptomatic infections, relapses and treatment failure (without drug resistance). Quiescence was recently demonstrated in Leishmania, but is still understudied.
One of the common features of quiescent cells is chromatin condensation, which is likely a mechanism to downregulate transcription, protect the genome, and keep the cell at minimal metabolic activity. It is currently unknown whether changes in chromatin conformation occur in Leishmania quiescent cells. In this project focusing on Leishmania donovani, we will investigate the chromatin accessibility during the entry, maintenance and exit of quiescence and correlate it with the observed transcriptional changes. We will consider two quiescence models based on starvation and exposure to drugs, respectively. These will be studied at single cell level by applying a cutting edge method combining an assay for transposase-accessible chromatin using sequencing (ATACseq) and
RNAseq, allowing the simultaneous measurements in the same cells across thousands of cells.

Project type:PhD project