About the Project
The prevalence of obesity leads to ever-increasing diabetes and cardiovascular disease, which puts added pressure on health service resources. High-energy fuels in our bloodstream (glucose) and storage depots (fat) are regulated by the brain, which respond to signals from peripheral organs. For example, the fat-derived hormone, leptin, acts on the brain to reduce appetite and increase energy expenditure. If we are to discover potential new therapies for the treatment of obesity and other metabolic disorders, we need to understand the regulatory pathways in the brain. We have discovered that blocking the actions of specific peptidergic messengers in the brain reduces leptin’s effects (e.g. Hawke et al., 2009; Bechtold et al., 2012; Dodd et al., 2014). Homeostatic mechanisms also interact with parts of the brain that mediate the reward value of food. In fact, we have recently described the actions of the first-ever peptide to act through central cannabinoid receptor to reduce food intake without causing deleterious side effects (e.g. Dodd et al., 2010 and 2013). In addition, we have now identified sets of genes in the brain that are unregulated in individuals susceptible to obesity. Our research includes the use of naturally-occurring mutants and transgenic mice, and a number of cutting-edge technologies to carry out such research; including conditional transgenics and the use of virally-mediated tracers and designer receptors. This helps us to understand how the brain controls appetite, metabolism and glucose balance, and will provide new avenues of research to develop drugs to treat metabolic diseases. The project will be suitable for candidates with experience in neuroscience or physiology.
References
Hawke, Z., Ivanov, T.R., Bechtold, D.A., Dhillon, H., Lowell, B.B. and Luckman, S.M., 2009, PACAP neurons in the hypothalamic ventromedial nucleus are targets of central leptin signaling. J. Neurosci. 29: 14828-14835.
Dodd, G.T., Mancini, G., Lutz, B. and Luckman, S.M., 2010, The peptide hemopressin acts through CB1 cannabinoid receptors to reduce food intake in rats and mice. J. Neurosci. 30: 7369-7376.
Bechtold, D.A., Sidibe, A., Saer, B.R.C., Li, J., Hand, L.E., Ivanova, E.A., Darras, V.M., Dam, J., Jockers, R., Luckman, S.M. and Loudon, A.S.I., 2012, A role for the melatonin related receptor, GPR50 in leptin signaling, adaptive thermogenesis and torpor. Current Biol. 22: 70-77.
Dodd, G.T., Worth, A.A., Hodkinson, D.J., Srivastava, R.K., Lutz, B., Williams, S.R. and Luckman, S.M., 2013, Central functional response to the novel peptide cannabinoid, hemopressin. Neuropharmacology 71: 27-36 (epub Mar 7).
Dodd, G.T., Worth, A.A., Nunn, N., Korpal, A.K., Bechtold, D.A., Allison, M.B., Myers, M.G., Statnick, M.A. and Luckman, S.M., 2014,The thermogenic effect of leptin is dependent on a distinct population of prolactin-releasing peptide (PrRP) neurons in the dorsomedial hypothalamus. Cell Metab. 20: 1-11 (epub Aug 28).