The Stem Cells and Regeneration group is interested in isolating the factors that bring about activation of adult stem cells during tissue regeneration after injury or tumor formation. To that end, the team studies the molecular mechanisms through which neural stem cells are activated and produce new nerve cells in the adult brain. The methods utilised in the lab include genetics, RNA-sequencing, high-end confocal microscopy and behavioral assays to test recovery of neural function. The team applies these methods in the adult fruit fly brain, within a region called the optic lobe. Recent work from the lab has resulted in the discovery of damage-responsive stem cells in this area and the identification of several candidate genes that are thought to underlie this process. Currently, the team is characterising these genes while concurrently working on identifying other brain regions that are able to regenerate. Ultimately, the team’s discoveries may lead to new therapies to facilitate tissue repair, such as brain regeneration after stroke, and preventing dysregulated stem cell proliferation that may lead to tumor formation.
How adult stem cells can switch from being dormant to actively dividing in situations relevant for tumor formation or tissue regeneration after injury
Genetics, RNA-sequencing, Confocal microscopy, Behavioural assays
Models and Regions
Entire brain / Fruit fly
Stem cell control
Many mammalian tissues contain pools of quiescent adult stem cells, which are only activated in pathological conditions or upon injury and have been proposed to act as a backup population. Regulation of stem cell quiescence and the intrinsic mechanisms by which cells sense and respond to injury-related signals are not well understood.
To unravel such mechanisms, we study recently discovered quiescent adult neural stem cell in the genetically accessible model organism Drosophila, which are activated upon traumatic brain injury by stab lesion (Fernandez-Hernandez et al., 2013)
To reach this goal, we perform whole genome expression profiling (microarrays and RNAseq) in combination with powerful functional RNAi assays and expression studies to validate candidate genes, followed by detailed characterization of conserved components.
Regenerative Neurogenesis and Function
We also seek to answer fundamental questions such as how adult-born neurons integrate into the mature brain and if their integration contributes to recovery of brain function after injury. To this end, we apply high-end microscopy, electrophysiology and behavioral assays to monitor performance after injury.
Courtship suppression assay to measure long-term memory in flies
Induction of JNK signalling shortly after injury.
Adult-born neurons in injured optic lobes.
Brain Repair in progress: Neuronal cell death and de novo neurogenesis.