De kloof overbruggen: Leishmania als paradigma voor het onderzoek naar de impact van genoomdiversiteit op metaboloomvariatie. (Leishma)
The genome and the metabolome are situated at both extremities of the modern dogma of molecular biology, respectively representing the genetic potential and the biological end-points, closest to the phenotype. Natural diversity of micro-organisms provides a dynamic context for innovative studies on the link between these two ‘-omics’. A Nepalese population of Leishmania donovani (Protozoa, Trypanosomatids) represents a unique model for such
studies by combining a very recent clonal origin and a high phenotypic diversity. Full genome sequencing of 30 clinical lines revealed a high homogeneity at sequence level, but a high diversity at structural level associated with major gene dosage. Hypothesising that gene dosage plays a major role in rapid evolutionary adaption of the parasite and the observed phenotypic diversity, we aim to characterise the metabolome of these clinical lines. With
a threefold approach, we will progressively strip down the complexity of the relationships between both sets of data. At first, the impact of natural genomic diversity will be measured within our natural population. Then, two experimental approaches will be applied to induce genomic variation in isogenic lines and track down metabolomic changes. We anticipate that this integrative approach will give an unprecedented insight into pathogen diversity.