Recent studies by the Center for Disease Control predict that there will be a sharp increase in the number of people with diabetes over the next 40 years. Similarly, over 34% of the US population (>72 million people) are obese, and thus at risk for a range of disorders including cancer, neurodegenerative diseases, and stroke. The World Health Organization estimates that at least 400 million adults are clinically obese worldwide, and predicts that this number will increase to 700 million by 2015. These trends have prompted widespread changes in public policy as well as a shift in biomedical research toward improving our understanding of the normal control of metabolism and how misregulation of these pathways can lead to disease.
Our lab is studying the regulation of metabolism using the fruit fly, Drosophila, as a model system. Remarkably, in spite of its small size and clear differences from mammals, many of the basic metabolic pathways are conserved through evolution from flies to humans. Flies have analogs of the basic tissues that control metabolism, including the equivalents of a liver, intestine, adipose tissue, pancreas, and kidneys. Many of the basic metabolic regulatory circuits are intact. Thus, for example, flies secrete insulin in response to elevated levels of circulating sugar, and mobilize stored energy in response to a hormone related to glucagon. Flies are also subject to similar metabolic disorders as people, and thus can acquire type 2 diabetes if exposed to a high sugar diet, or can more than double their fat content on a high fat diet. They are also responsive to drugs used to treat metabolic disorders, such as the weight loss drug Alli (Orlistat). Our lab is studying the basic molecular mechanisms by which metabolism is controlled using the wide range of genetic tools available in Drosophila. We seek to uncover fundamental aspects of metabolic regulation that are conserved through evolution, with the aim of preventing and curing human disease.
There are three lines of study underway in the Thummel lab. Click below to find out more:
- Transcriptional regulation of metabolism by nuclear receptors
- Functions for evolutionarily conserved mitochondrial proteins
- The transgenerational inheritance of metabolic state