Gould group ::

Regulation of growth and metabolism

All organisms regulate their growth according to internal genetic programmes and the availability of nutrients from the environment. As human and other animal embryos develop, they increase in size dramatically. We wish to identify the nutritional factors and genetic networks that promote embryonic growth and, equally importantly, those that shut it down in adults. This research also aims to shed light on the process of tumour formation and the complex interactions between nutrition and genes influencing obesity and diabetes (1).

Research in the laboratory mainly utilises the fruit fly Drosophila (2), a model organism that shares many genes with mammals (3) and has contributed to our understanding of several different aspects of human health and disease. We have recently identified a group of genes expressed in the neural stem cells (4) of Drosophila (called neuroblasts) that are essential for switching off growth of the nervous system and preventing neural tumors in adults. We have also identified /Drosophila/ hepatocyte cells (called oenocytes) that express many enzymes metabolising lipids (5) and are essential for regulating growth and body-fat content. These cells can also be used to model aspects of human hepatic steatosis (fatty liver) (6).

Drosophila neural stem cells over-proliferate when cell death is blocked

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Each Drosophila neuroblast in the posterior region of the central nervous system normally generates a group of ~8 neurons (wild type, left) whereas those lacking the cell death genes reaper, hid and grim produce ~36 neurons (apoptotic mutant, right).

Steatosis in hepatocyte-like cells of Drosophila

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Intracellular fat droplets, stained with Oil Red O, in the oenocytes of Drosophila larvae that are normal (wild type, left) or that overexpress PTEN, an inhibitor of the Insulin/PI3-kinase pathway, in the fat body (insulin-compromised, right).

External links

1. What is diabetes? - NHS
2. Flybase - A Database of Drosophila Genes and Genomes
3. Homophila - a human disease to Drosophila gene database
4. Neural stem cells - see Adult neurogenesis on Scholarpedia
5. The Lipid Library
6. Fruit flies provide liver hope - BBC

[Page last updated 3 June 2008]

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