Douglas L. Crawford

The research in my laboratory investigates the functional importance of natural variation; specifically the variation in gene expression,the molecular mechanisms that affect the variation in expression and the physiological consequences of this variation. To better understand the biological importance of this variation, my researchgroup integrates different levels of biological understanding: genes, genomics, gene expression, enzyme function, and physiology. These analyses are strengthened by evolutionary analyses to distinguish random neutral variation from variation due to natural selection. It is this combination of approaches, evolutionary biology with physiological genomics, that is my laboratory’s strength.

To better understand the biological importance of gene expression, we have developed Functional Genomics tools for the teleost fish Fundulus. These tools include greater than 74,000 EST which form 12,000 unique Fundulus cDNAs for microarray studies, bioinformatics to annotate and investigate these genes, and statistical capabilities to analyze large microarray datasets. Utilizing these tools we are investigating the relationship between how changes in mRNAs relate to changes in protein concentration, physiological performance, ecological setting and evolutionary divergence. This broad approach requires a diversity of research methods and critical thought, and it is now providing important insights into the causes and consequences of phenotypic variation. For example, our recent microarray studies demonstrate: 1) that patterns of gene expression explain the significant variation in cardiac performance; 2) the genes that contribute to the differences in cardiac metabolism (i.e., functionally important genes) vary among individuals and 3) that much of the variation in gene expression is evolving by natural selection. These data sets suggest that much of the variation in gene expression is biologically important, but the relationship between gene expression and biological function is complex.

Using evolution to understand molecular physiology and using molecular traits to investigate evolutionary processes is the foundation of my research. We pursue these goals to better understand individual variation, the biological importance of this variation and human health and disease.

Oleksiak, M.F., Churchill, G. & Crawford, D.L. Variation in gene expression within and among natural populations. Nature Genetics, (2002). 32: p. 261-266.

Crawford, D. L. (2002). Evolution of physiological adapatation. In Cell and Molecular Responses to Stress, vol. 3 eds. K. B. Storey and J. M. Storey.  NY: Elsevier Publishing.

Kolell, K.J. & Crawford, D.L. Evolution of Sp Transcription Factors. Molecular & Biology and Evolution (2002) 19: 116-222.

Oleksiak, M.F., Kolell, K. & Crawford, D.L.  The utility of natural populations for microarray analyses: isolation of genes necessary for functional genomic studies. Marine Biotechnology (2001) 3:S203-S211.

Crawford, D.L. Functional genomics does not have to be limited to a few select organisms. GenomeBiology ( 2001) http://www.genomebiology.com/2001/2/1/interactions/1001/(2001).

Podrabsky, J. E., C. Javillonar, S. C. Hand and D. L. Crawford  (2000).  Intraspecific Variation in Aerobic Metabolism and Glycolytic Enzyme Expression in Heart Ventricles from Fundulus heteroclitus.  Am J. Physiology 2000  279:R2344-R2348.

Crawford, D. L., Segal, J. A. and Barnett, J. L. (1999b). Evolutionary analysis of TATA-less proximal promoter function. Molecular Biology & Evolution 16, 194-207.

Pierce, V. A. and Crawford, D. L. (1997a). Phylogenetic analysis of glycolytic enzyme expression. Science 275, 256-259.

Pierce, V. A. and Crawford, D. L. (1997b). Phylogenetic analysis of thermal acclimation of the glycolytic enzymes in the genus Fundulus. Physiological Zoology 70, 597-609.

Crawford, D. L. and Powers, D. A. (1989).  Molecular basis of evolutionary adaptation at the lactate dehydrogenase-B locus in the fish Fundulus heteroclitus. Proceedings of the National Academy of Sciences of the United States of America 86, 9365-9369.

Segal, J. A. and Crawford, D. L. (1994). LDH-B enzyme expression: the mechanisms of altered gene expression in acclimation and evolutionary adaptation. American Journal of Physiology 267, R1150-3.

Crawford, D. L. and Rissing, S. W. (1983). Regulation of recruitment by individual scouts in Formica Oreas Wheeler (Hymenoptera, Formicidae). Insectes Sociaux 30, 177-183