Models of disease and drug delivery in cancer
We are investigating the roles of glucocorticoid-induced leucine zipper (GILZ) in cancer development and neoplastic diseases. Cell proliferation is regulated by GILZ via oncogenic Ras-dependent transformation which affects tissue-specific cell differentiation and apoptosis. The aim of this project is to determine whether GILZ causes changes in mitochondrial respiratory chain enzymes and affecting cellular energy metabolism.
The aim of this project is to determine how GILZ expression can cause changes in cellular pathways that regulate energy balance and proliferation. This will be achieved by assessment of metabolic activities in various tissues from available animal gene knock-out models. We will investigate the expression levels and epigenetic modification of genes involved in the glucocorticoid response and relate this to energy expenditure. These studies will help to develop highly-selective drug targeting using rapid accumulation within mitochondria, driven by the membrane potential. Techniques used include cell culture, enzymology, respirometry, confocal microscopy, spectroscopy, western blotting, molecular biology and biochemistry.
The project promises to provide important insight into how the GILZ-dependent pathway links cell proliferation with mitochondrial metabolism leading to neoplastic diseases and common cancer.
This project will be supervised by Dr Alexander Galkin of Queen's School of Biological Sciences and Professor Carlo Riccardi of the University of Perugia.
The successful applicant will be awarded a Queen's University EU/International Studentship (View Website).
Glucocorticoid-induced leucine zipper (GILZ) and long GILZ inhibit myogenic differentiation and mediate anti-myogenic effects of glucocorticoids. Bruscoli S, Donato V, Velardi E, Di Sante M, Migliorati G, Donato R, Riccardi C. J Biol Chem. 2010, 285:10385-96.
Lack of oxygen deactivates mitochondrial complex I: implications for ischemic injury? Galkin A, Abramov AY, Frakich N, Duchen MR, Moncada S. J Biol Chem. 2009 284:36055-61.