Inside the guts of fruit flies Scientists use sophisticated, systems techniques to gain deeper insights into the genetic and environmental factors that influence the development of Drosophila melanogaster. The interaction between Drosophila melanogaster and the microbiota in their gut has a major influence in this respect, a topic at the heart of Professors François Leulier’s and Bart Deplancke’s research. There is a
long history of geneticists using Drosophila melanogaster (fruit flies) as a model species in research, as scientists can use sophisticated techniques to probe the genetic and environmental factors that influence their development. One of these developed at Professor Bart Deplancke’s lab at EPFL in Lausanne is BRB-seq. “There’s a clear need to come up with cheaper bulk transcriptomics approaches in order to derive meaningful, quantitative data from lots of tissues from many individuals. With BRB-seq, we essentially barcode the samples very early on during the sequencing library preparation process, which reduces cost and increases throughput,” he explains.
Systems genetics of Host/Microbiota mutualism in Drosophila melanogaster - DGRPmutualism Project Coordinator, Prof Bart Deplancke EPFL Life Sciences and Engineering T: +41 21 693 18 21 E: bart.deplancke@epfl.ch W: https://deplanckelab.epfl.ch/ W: http://igfl.ens-lyon.fr/equipes/f.-leulierfunctional-genomics-of-host-intestinalbacteria-interactions
Bart Deplancke (left) is the head of the Laboratory of Systems Biology and Genetics at EPFL in Lausanne, where he is an Associate Professor. The central focus of the laboratory is on understanding genome organization, regulation and variation. Francois Leulier (centre) is a biologist at IGFL in Lyon, with a background in genetics. Among his major research interests is identifying the molecular basis of the beneficial effects of intestinal microbiota on animal growth. Dali Ma (right), the project’s lead scientist.
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This technique is being applied in a collaborative project which brings together researchers from Prof. Deplancke’s lab and that of Prof. Leulier at the IGF in Lyon. The aim here is to investigate the interaction between microbiota species and the host fruit fly. “There are thousands of different microbiota species in the human gut, many of which we cannot cultivate. On the other hand, we can cultivate all the bacteria that we find in the fruit fly gut,” outlines Dr. Dali Ma, the project’s lead scientist. Researchers in the project are screening the Drosophila melanogaster Genetic Reference Panel (DGRP), a set of highly in-bred fly strains. “Even though these different strains carry an enormous amount of genetic diversity, they all look very similar,” says Dr. Ma.
found that these bacteria buffer phenotypic diversity not only at the organismal level, but also at the molecular level. “The BRBseq technique allowed us to look at many transcriptomes of both these populations. We could see essentially that the one treated with the bacteria was largely less variable than the one that wasn’t,” explains Professor Deplancke. Researchers are now aiming to draw deeper insights into the mechanisms by which a species produces the same developmental phenotype, despite high levels of genetic diversity. “A paper has been published suggesting that the production of reactive oxygen species (ROS) is also involved,” says Dr Ma. The production of ROS was long considered to be very damaging, as it causes ageing and cellular damage, yet it
If you remove all the bacteria from fruit flies and put them on a normal, protein and carbohydrate-rich diet, then those flies grow up normally. When we put them on a restrictive diet, we start seeing a developmental divide. Robustness This is related to the idea of robustness, broadly speaking a process that ensures there is a certain phenotypic homogeneity amongst a population, even though they may have a high level of genetic diversity. The concept of cryptic genetic variants (CGV) comes into play here. “An organism is essentially neutral when it is not challenged. So a population living in normal physiological conditions with these variants does not act,” explains Dr. Ma. If the physiological conditions change then an organism needs to adapt; Dr. Ma is probing how fruit flies adapt to a nutrient-poor diet. “If you remove all the germs from fruit flies and put them on a normal, protein and carbohydraterich diet, then we find that those flies grow up normally,” she says. “However, when we put them on a restrictive diet, with little protein, we start seeing a developmental divide.” The population of germ-free Drosophila with these different diets was found to show increased variation in developmental traits, which was reduced in a population to which Lactobacillus plantarum bacteria were added back at the embryonic stage. Researchers have
has now been shown that lots of physiological and developmental processes depend on correct ROS signalling. “For example, ROS signalling helps to organise the cyto-skeleton. ROS is really a double-edged sword,” says Dr. Ma. A major challenge in this research is to build a deeper understanding of how microbiota preserve genetic diversity, while at the same time driving evolutionary change. While aware of the bigger picture, Dr. Ma plans to focus her attention on genetic mechanisms. “We want to look for things mechanistically, to see how the bacteria channels growth,” she says.
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