Characterizing the Gene Regulatory Networks Mediating Gut Immunocompetence in Drosophila
In gut-bearing organisms, food intake and digestion require continuous exposure to the environment, including commensal and pathogenic microorganisms. This constant exposure has led them to develop complex mechanisms to defend themselves against infectious agents while remaining tolerant to the presence of non-pathogenic microorganisms. Important progress has been made to elucidate the biological processes underlying gut immunocompetence, revealing an intricate interplay between immunological, stress, and neuronal signaling as well as gut regeneration and wound repair. However, how this multilayered regulatory network is encoded at the molecular level and how genetic variation of the host species contributes to this trait is still poorly understood. In our lab, we use an interdisciplinary approach, combining regulatory genomics and bioinformatics, to elucidate the genetic and molecular mechanisms underlying gut immunocompetence and its variation in Drosophila melanogaster. Using laboratory strains, transgenics, as well as panels of flies from natural populations, we are determining the regulatory targets of transcription factors involved in the interplay between the immune response pathways, relating them to known physiological outputs, and computationally mining the genetic variants that may lie at the basis of the observed phenotypic variation (resistance to infection).
Metabolic Phenotyping of the Drosophila Genetic Reference Panel
Mitochondrial dysfunction is increasingly linked to neurodegenerative and metabolic diseases that emerge during aging. Although numerous genetic mutations are known to affect aging, the complex molecular, metabolic and mitochondrial networks involved are poorly understood. In our project we use natural variation in Drosophila melanogaster as a model system to characterize mitochondrial networks and study how these influence aging. Using the Drosophila Genetic Reference Panel (DGRP), containing ~200 sequenced inbred fly lines, we specifically aim to quantitatively map (mitochondrial) genetic determinants of phenotypes relevant to the process of aging (e.g. fat accumulation and activity).