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