Outstanding Questions

The main objective of the de Bakker lab is to unveil the genetically encoded mechanisms of vertebrate brain aging. To achieve this objective, we investigate which genetic and molecular factors govern differences in brain aging rates between species. Ultimately, by uncovering the mechanisms of brain aging, we aim to pave the way for the development of strategies to delay brain aging and associated neurodegenerative diseases in humans.

To accomplish this objective, we address three independent aims:

Aim 1: Identification of genetic loci, mRNAs, proteins, and molecular pathways through cross-species comparison using a multi-omics approach.

Aim 2: Identification of bioactive compounds and genetic modifications with the potential to delay brain aging. Bioinformatics and artificial intelligence are used to analyze datasets produced in Aim 1, as well as publicly available datasets. Genetic engineering and molecular chemistry are harnessed to produce compounds and transgenic killifish strains with the potential to delay brain aging.

Aim 3: Delaying brain aging in the turquoise killifish. Using compounds and killifish strains produced either in Aim 2 or by collaborators, we endeavor to delay brain aging in turquoise killifish. Relevance to human aging and disease is assessed using human brain tissues and publicly available datasets.