How infection interacts with genetic determinants to modify health outcomes

Project leader: Dr James Gilchrist, NIHR Clinical Lecturer

James joined the Fairfax group at the MRC Weatherall Institute of Molecular Medicine (MRC WIMM) in 2018, supported by an NIHR academic clinical lectureship. His work aims to understand how environmental exposures, in particular CMV infection, interact with genetic determinants of immune cell function and how this interaction modifies health outcomes.

James has a longstanding interest in the host factors that determine susceptibility to invasive nontyphoidal Salmonella (NTS) infection in African populations (MacLennan et al 2010, Gilchrist et al 2015, Wang et al 2017, MacLennan et al 2017 - PMIDs: 20413503, 26109132, 28345042, 29216183, respectively). The primary output from his DPhil was the publication of the first genome-wide association study of NTS bacteraemia (Gilchrist et al 2018, PMID: 29523850). This identified functional variation in Natural Killer (NK) cells as a determinant of NTS susceptibility in African children. He has pursued this area of interest during his time at the MRC WIMM, investigating the genetics of gene expression in naïve NK cells, and how this is perturbed following stimulation.

Alongside this, James continues to have an active interest in the host genetic determinants of invasive infection in African populations. He has recently completed a project describing how G6PD deficiency modifies risk of pneumococcal bacteraemia in Kenyan children (Gilchrist et al 2020, PMID: 32536341). He is leading a collaborative study investigating the human genetic determinants of leprosy in Malian and Malawian populations. He is also leading a collaborative project, supported by an Academy of Medical Sciences Starter Grant for Clinical Lecturers, to describe the host genetic factors that modify risk of rotavirus disease and acquisition of immunity in Kenyan and Ugandan children (see study schematic below).

December 2020