Determining T lymphocytes transcriptional profiles and their role in defining distinct malaria outcomes in an endemic region using population and single cell gene expression analysis

In locations with intense transmission of malaria, infections by the parasites leads to distinct clinical outcomes in humans. These can be acute or severe malaria and asymptomatic disease. The immunological mechanism(s) underpinning these different fates is unknown. Recent experiments have established that T lymphocytes are critical in shaping the protective immune response.

However, they remain unexplored within malaria infections in field settings partly due to the limitations of previous methods.

The recent upsurge in sequencing technologies combined with the ability to capture and measure entire sets of expressed genes have enhanced our capability to understand the functional roles of genes in complex biological processes.

These techniques, referred to as RNA sequencing (RNAseq) can now be applied to population of cells (bulk-RNAseq) and individual cells (scRNA-seq).Using both techniques we will profile T cells from humans infected by malaria in endemic regions.

We will investigate clinical and asymptomatic infections arising from the most virulent species, Plasmodium falciparum, to understand the basis for clinical immunity.

To this end we will simultaneously acquire other measurements that are critical in determining response (e.g. antibody profiles) and use an integrated approach to gain a holistic understanding of the complex process.

These results will advance our understanding and may motivate rational approaches for designing drugs and vaccines against malaria.