"The rising prevalence of obesity and associated co-morbidities such as Type 2 diabetes, cardiovascular disease and certain cancers represents a major threat to public health in Europe and worldwide. It can be argued that modern westernized environments are obesity promoting due to unprecedented economic growth, decreased incidence of infectious disease, nearly unlimited food supply, a wide availability of high fat, highly palatable pre-prepared foods, large portion sizes and technological advances leading to a more sedentary lifestyles. The influence on the whole population of environmental factors is undoubtedly powerful, but one remarkable feature of the obesity epidemic is the persistence of enormous individual variation in body weight throughout the population. Individual differences seem to be increasing in both children and adults, with the lean staying lean while the obese become more obese, which indicates that individuals interact differently with the ‘obesogenic’ environment. There is strong evidence that within a population the variance in weight is largely genetically determined. Given that common obesity results from an imbalance between energy intake and expenditure, it is highly likely that this interaction occurs partly through individual variation in appetite and eating behaviours. To date virtually all research based at finding genes related to obesity has focussed on the upper end of the body mass index (BMI) distribution. As part of this proposal I propose a complementary gene finding strategy that focuses on the lowest end of the BMI distribution in order to find genes that confer resistance to obesity in an obesogenic society. The identification of such genes may explain why some individuals do not become obese despite environmental provocation. Insights into the biology of thinness and obesity resistance could lead to rational preventative and therapeutic strategies for obesity."