From genome to the field: a global study of pathogen genetic and metabolic diversity and its relationship to clinical phenotypes (GeMini)

Characterising the
diversity of pathogen populations is a major key for understanding the clinical polymorphism of infectious diseases. The
past 2 years have brought new technologies
that may revolutionise this field of research as they bring unprecedented potential for global pathogen exploration. On one
hand, economic high-throughput sequencing
technologies allow whole genome comparative analyses of multiple strains of a given species. On the other hand, advances in
mass-spectrometry facilitate comprehensive
metabolite profiling, hereby providing access to the ultimate expression of an organism’s genotype, the closest correlate
to the phenotype. The integration of the new genome and metabolome technologies offer an unparalleled source of
data, but its exploitation for an effective translation to health
problems require alliances between the high-tech
specialised centres currently developing the new technologies and institutions engaged
in the field, at the front of infectious diseases. For this purpose, we propose
to build at ITM a multidisciplinary
research platform with a holistic perception of diversity, equipped to analyse
and interpret the massive data output of genome and metabolome studies.
The prototype platform will be built in collaboration with Sanger Institute and
Strathclyde University. It will be validated
using as paradigm treatment failure in visceral leishmaniasis and drug
resistance in Leishmania donovani.
Isolates from our previous clinical studies
in Nepal will be submitted to genome- and metabolome-wide comparisons, and genetic and metabolic signatures
associated with various drug resistance
phenotypes will be identified, interpreted and validated. Our platform aims to interact with similar initiatives targeting other
pathogens or the human host. GeMInI is expected
to have a major impact by boosting post-genomic translational research in general, but also more specifically by bridging
research and control of neglected diseases.