Proper energy allocation underlies metabolic health and requires the evolved cooperation of the mitochondrial and nuclear genomes, embedded in a context of diet. Human metabolic disease is increasingly viewed in the framework of energy homeostasis. Because energetic processes are highly conserved, this study of Drosophila addresses key issues for understanding human metabolic disease - the physiological consequences of mitochondrial-nuclear interactions and the role that diet plays in mediating energy metabolism. This project tests hypotheses regarding genetic relationships between energetic biochemical pathways, energy storage, metabolic rate and performance phenotypes 1) in healthy Drosophila, 2) in Drosophila with disrupted mito-nuclear genomes and 3) under normal and calorie- restricted diets. Mito-nuclear disruptions will be created by introgressing mtDNA from D. simulans into a D. melanogaster nuclear background. We will also quantify mRNA expression levels of regulatory genes involved in communication between genomes. The results will identify candidate enzyme-encoding and regulatory genes that can be further investigated for functional roles in maintaining metabolic health. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM076812-01
Application #
7052535
Study Section
Special Emphasis Panel (ZRG1-F08 (20))
Program Officer
Dearolf, Charles R
Project Start
2006-03-01
Project End
2009-02-28
Budget Start
2006-03-01
Budget End
2007-02-28
Support Year
1
Fiscal Year
2006
Total Cost
$45,976
Indirect Cost
Name
Brown University
Department
Biology
Type
Schools of Medicine
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code
02912
Meiklejohn, Colin D; Holmbeck, Marissa A; Siddiq, Mohammad A et al. (2013) An Incompatibility between a mitochondrial tRNA and its nuclear-encoded tRNA synthetase compromises development and fitness in Drosophila. PLoS Genet 9:e1003238
Montooth, Kristi L; Meiklejohn, Colin D; Abt, Dawn N et al. (2010) Mitochondrial-nuclear epistasis affects fitness within species but does not contribute to fixed incompatibilities between species of Drosophila. Evolution 64:3364-79
Montooth, Kristi L; Abt, Dawn N; Hofmann, Jeffrey W et al. (2009) Comparative genomics of Drosophila mtDNA: Novel features of conservation and change across functional domains and lineages. J Mol Evol 69:94-114
Meiklejohn, Colin D; Montooth, Kristi L; Rand, David M (2007) Positive and negative selection on the mitochondrial genome. Trends Genet 23:259-63