A healthy human fetus grows at an impressive rate as it develops inside the mother's uterus. In about 5% of pregnancies, however, nutrients and oxygen cannot be efficiently supplied from mother to fetus. When this metabolic stress occurs, it is not always possible for the fetal body to continue to grow at the normal rate. Nevertheless, in many of these cases, the growth of the fetal brain remains remarkably unperturbed.
Work in the Physiology and Metabolism Laboratory aims to identify as yet unknown protective processes that spare the growth of the brain over that of the body. Towards this goal, Alex and coworkers have previously modelled some aspects of brain sparing in the fruit fly Drosophila, which shares many genes with humans – including about three-quarters of those linked to human diseases. Although the brain of Drosophila is much smaller and less complex than that of humans, they both contain very similar cell types - such as neural stem cells, neurons, and glia.
The research funded by the NC3Rs grant will use single-cell sequencing to produce an atlas of the genes expressed in every one of the tens of thousands of cells in the normal versus the metabolically stressed Drosophila brain. In this way, genes can be identified that are active during the brain sparing process in the fly, and their equivalents can also be tested in mammals. The atlas will be used to inform genetic approaches designed to pinpoint how different cell types in the brain communicate with each other during brain sparing. This atlas may also help researchers to work out how metabolism in the mammalian brain is linked to health and disease.
"We hope to shed light on how different cell types in the brain use metabolic circuits to protect each other from the potentially harmful effects of malnutrition and other stresses. From a practical standpoint, I am really looking forward to working with the Advanced Sequencing as well as the Biostatistics and Bioinformatics STPs on this exciting project," - Adrien Franchet
"An enduring legacy of this project will be an open-access web atlas that can be used by all scientists interested in brain metabolism," - Alex Gould
We hope to shed light on how different cell types in the brain use metabolic circuits to protect each other from the potentially harmful effects of malnutrition and other stresses. From a practical standpoint, I am really looking forward to working with the Advanced Sequencing as well as the Biostatistics and Bioinformatics STPs on this exciting project
