The research was carried out at the University of Sheffield in laboratories supported by the Biotechnology and Biological Sciences Research Council (BBSRC). This work is reported in the current edition of BBSRC Business, the quarterly research highlights magazine of the Biotechnology and Biological Sciences Research Council.

Professor Richard Ross, Chief Scientific Officer of Asterion Ltd., said: "A big challenge for biological therapeutics is that they are broken down rapidly in the body. The technology developed by Asterion Ltd. is based on basic structural biology work that has provided us with the knowledge necessary to develop longer acting drugs. This is a major advantage for patients, as it means monthly injections rather than daily injections."

Professor Ross, along with fellow founding directors Professors Pete Artymiuk and Jon Sayers have shown that it is possible to engineer proteins that can intervene when there is a deficiency in hormones. Their initial experiments involved fusing different elements of hormone and receptor in order to treat a growth disorders such as short stature (a deficiency in growth hormone).

Professor Ross continued: "Our patented and versatile therapeutic platform technology ProFuse TM, could also tackle major diseases such as some cancers, anaemia, infertility and diabetes. Under normal circumstances hormones of the type known as cytokine hormones - growth hormone for example - circulate in the blood and are bound to proteins that prevent them from being degraded. The basic structural biology work we have done in the past means that we can see the interaction between the hormone and the binding protein in exquisite detail. Our understanding of this structural information means that we can rationally design drugs that consist of this pairing of hormone and binding protein that still allows them to activate the cell surface receptor. In this situation, the hormone portion of the drug is better protected in the circulation from degradation and so it has a much longer effective life in the body."

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An alternate theory proposed that release of the GABA neurotransmitter was mediating the function of AgRP neurons, an idea that had long been postulated but never examined.

To test this hypothesis, Tong and his colleagues generated a group of mice with disrupted release of GABA specifically from the AgRP neurons. As predicted, the genetically altered mice exhibited profound metabolic changes.

"The mice with AgRP neuron-specific disruption of GABA release were lean, had higher energy expenditure and showed resistance to diet-induced obesity," says Tong. "We also found that these animals showed reduced food intake response to the hormone ghrelin. This suggests to us that the neurocircuit engaging GABA release from the AgRP neurons mediates at least part of ghrelin's appetite-stimulating action."

A series of studies to examine the function of glutamate and GABA release from other groups of neurons are currently underway as investigators continue to dissect the brain's neurocircuitry.

"As these new findings demonstrate, GABA release is an important component that mediates the function of AgRP neurons," says Tong. "Discoveries such as this will ultimately help us to design an efficient strategy to tackle the current epidemic of obesity and metabolic disease."

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