Daniela

Drummond-Barbosa

,

PhD

Nutrient availability has well documented effects on tissue stem cell lineages in a wide range of multicellular organisms; yet, the molecular, cellular and physiological mechanisms underpinning stem cell control by diet, metabolism or hormones in vivo remains largely unexplored. Dr. Drummond-Barbosa pioneered using Drosophila to study adult stem cell regulation by diet. She showed that ovarian stem cells and their descendants proliferate and grow faster on rich relative to poor diets. Her laboratory subsequently played a major role in delineating how insulin-like peptides, ecdysone, and the Target of Rapamycin (TOR) nutrient sensor mediate this response by acting in the ovary. More recently, Dr. Drummond-Barbosa’s research program has been addressing the link between adipocyte physiology and stem cell biology. This question is particularly relevant to the current obesity epidemic and to the poorly understood connection between obesity and cancers. Using a combination of genetic tools that allow us to manipulate gene function exclusively in adipocytes, they showed that amino acid sensing by adult adipocytes has highly specific effects on the GSC lineage in the Drosophila ovary: (1) low amino acid levels trigger the evolutionarily conserved amino acid response pathway through unloaded tRNA-mediated activation of the GCN2 kinase within adipocytes to remotely control GSC numbers in the ovary; and (2) amino acids modulate TOR signaling within adipocytes to modulate the efficiency of oocyte ovulation. In another study, they conducted an isobaric tags for relative and absolute quantification (iTRAQ) proteomic analysis to identify diet-regulated adipocyte metabolic pathways that contribute to the control of the GSC lineage. On a rich (relative to poor) diet, adipocyte Hexokinase-C and metabolic enzymes involved in pyruvate/acetyl-coA production are upregulated, promoting a shift of glucose metabolism towards macromolecule biosynthesis. Adipocyte-specific knockdown shows that these enzymes support early GSC progeny survival. Further, enzymes catalyzing fatty acid oxidation and phosphatidylethanolamine synthesis in adipocytes promote GSC maintenance, whereas lipid and iron transport from adipocytes controls vitellogenesis and GSC number, respectively. These results point to extensive communication between adipocytes and the ovary, and underscore the complexity of the physiological network that modulates stem cell behavior. Ongoing/future efforts of the Drummond-Barbosa research group aim at identifying new systemic mediators of diet, with special emphasis on adipocyte- and neural-derived factors.