Herchel Smith Professor of Molecular Biology
Andrea Brand is accepting applications for PhD students.
Discovering how stem cells are maintained in a multipotent state and how their progeny differentiate into distinct cellular fates is a key step in the therapeutic use of stem cells to repair tissues after damage or disease. We are investigating the genetic networks that regulate neural stem cell behaviour. Neural stem cells in the adult brain exist primarily in a quiescent state but can be reactivated in response to changing physiological conditions. How do stem cells sense and respond to metabolic changes? In the Drosophila central nervous system, quiescent neural stem cells are reactivated synchronously in response to a nutritional stimulus. We showed that feeding triggers insulin production by blood-brain barrier glial cells, activating the insulin/IGF pathway in underlying neural stem cells and stimulating their growth and proliferation. More recently, we discovered that gap junctions in the blood-brain barrier glia mediate the influence of metabolic changes on stem cell behaviour, enabling glia to respond to nutritional signals and reactivate quiescent stem cells.
The ability to reprogram differentiated cells into a pluripotent state has revealed that the differentiated state is plastic and reversible. Mechanisms must be in place to prevent neurons from dedifferentiating to a multipotent, stem cell-like state. We discovered that the BTB-Zn finger transcription factor, Lola, is required to maintain neurons in a differentiated state. In lola mutants, neurons dedifferentiate, turn on neural stem cell genes and begin to divide, forming tumours. Thus, neurons rather than stem cells or intermediate progenitors are the tumour-initiating cells in lola mutants.
Cell-type specific transcriptional profiling is key to understanding cell fate specification and function. We developed ‘Targeted DamID’ (TaDa) to enable cell-specific profiling without cell isolation. TaDa permits genome-wide profiling of DNA- or chromatin-binding proteins without cell sorting, fixation or affinity purification.
Jelle Van Den Ameele
Spéder P, Brand AH, (2014), Gap junction proteins in the blood-brain barrier control nutrient-dependent reactivation of Drosophila neural stem cells, Developmental Cell, 30, 309-321.
Southall TD, Davidson CM, Miller C, Carr A, Brand AH, (2014), Dedifferentiation of neurons precedes tumour formation in lola mutants, Developmental Cell, 28, 685-96
Gold KS, Brand AH, (2014), Optix defines a neuroepithelial compartment in the optic lobe of the Drosophila brain, Neural Development, 9,18; DOI: 10.1186/1749-8104-9-18
Southall TD, Gold KS, Egger B, Davidson CM, Caygill EE, Marshall OJ, Brand AH, (2013), Cell type-specific profiling of gene expression and chromatin binding without cell isolation: Assaying RNA Pol II occupancy in neural stem cells, Developmental Cell, 26, 101-112.
Cheetham SW, Brand AH, (2013), Insulin finds its niche, Science, 340, 817-818
Chell JM, Brand AH, (2010), Nutrition-responsive glia control exit of neural stem cells from quiescence, Cell, 143, 1161-73