Boosting Immunity Through Diet: Exploring How Low-Protein Diets Reshape Blood Stem Cell and Natural Killer Cell Responses to Pathogens

Background:
Western diets rich in fats and sugars are linked to obesity and more frequent infections. In contrast, plant-based diets have been associated with increased longevity and decreased infections in the elderly. Transitioning to a plant-based diet typically involves decreased protein intake through reduced meat consumption. However, the impact of low-protein diet on human health, particularly immune function, remains poorly understood. My group in collaboration with the Beraza group has recently shown that a low protein diet improves the immune response to bacterial infection[1].

Aim:
This project will investigate the mechanisms through which Natural Killer (NK)[2,3] cells enhance the immune response in low protein diets. To achieve this the student will employ cutting-edge FACS cell isolation, single-cell RNA sequencing, lineage tracing[4], metabolomic[5], and bioinformatic[6,7] techniques established in the Wojtowicz, Beraza, and Haerty groups.
Objectives:
1. Characterise the functional changes to NK cells during low-protein diets.
2. Identify the molecular and ancestry changes to NK cells upon infection during low-protein diets.
3. Either the identification and validation of genes that enhance NK cell production in vitro using CRISPR-Cas9 or utilising metabolomics to study the cause of enhanced NK cell cytotoxicity during low-protein diets.

Supervisory team, collaborations and the environment:
The student will be primarily based in the Wojtowicz lab, but will collaborate closely with the Beraza and Haerty groups. This will give them a strong and experienced supervisory team with expertise in metabolomic, single cell and computational methods. Established collaborations with pharmaceutical companies will allow the student to translate their findings into industry. The student will have access to extensive training and career development opportunities at EI, QIB, and as part of the Norwich Biosciences Doctoral Training Partnership.

References

10.1038/s42003-024-06932-w

10.1002/hep.25694

10.1084/jem.20082152

10.1186/s13059-023-02976-z

doi:10.1002/hep.31228, 6.doi:10.1186/s12864-021-08261-2, 7.doi:10.1038/s42003-023-04936-6