Untitled Document


Laura K. Reed
Research
Home	My research interests lie at the intersection of quantitative genetics and population genetics, where I explore the evolution of complex traits such as metabolic disease that are the result of multiple genetic effects and the environment. Historically, there are two basic approaches to understanding biology. The first involves dirt-under-your-fingernails fieldwork to characterize systems in their ecological context where they display all of their fascinating natural genetic and environmental variation. And the second seeks a complete understanding of a few genetic systems, such as the OregonR strain of Drosophila melanogaster, in the tightly controlled environment of the laboratory. Both of these approaches are crucial to our accelerating understanding of how life works. The next major innovations are coming as these two approaches meld through the technological advances caught under the umbrella of systems biology. By unifying dirty and sterile biology through systems biology, I am trying to understand the genetic and environmental architecture of natural variation.
Mechanistic Origins of Natural Phenotyptic Variation
	To understand disease, ultimately we have to understand each omics level, how it evolves, and the mechanisms by which it can be perturbed. Phenotypic variation derives not only from genetic variation but also from the environment that can introduce both predictable and random perturbation of the physiological system. Metabolic homeostasis is achieved through interactions between different physiological or omics levels within an organism, and by feedback into the evolutionary genetics of the species through fitness effects.
*A Drosophila* Model for Metabolic Syndrome**
My primary current and future research plans use systems biology to correlate empirical data from across physiological levels such as RNA and metabolites, to decipher the relative contribution of natural genetic variation and environment to metabolic diseases like obesity and type-2 diabetes. Specifically, I am characterizing how variation in metabolic disease phenotypes maps to the metabolic pathway, by integrating metabolomic profiling with phenotypic, genomic, and gene expression data.
Metabolic Syndrome (MetS) is a constellation of symptoms such as obesity, elevated blood lipids, and insulin resistance that are predictive of type-2 diabetes and cardiovascular disease. MetS is a recently developed syndrome caused by our increased calorie intake and decreased exercise that exposes cryptic genetic variation: some people can eat high-fat, high-sugar diets without adverse impact while others are highly sensitive to their diet. My research explores these effects using Drosophila, which also harbor cryptic genetic variation for disease, as a model to characterize the architecture of genotype-by-environment interactions of human-like metabolic disorders. With this charismatic model organism, I gain all the advantages of a carefully dissected metabolic and genetic system with substantial metabolic similarity to humans, while also being able to sample natural variation with high throughput genomic methods. Thus, using Drosophila, I can gain insights into a genetically complex disease that affects humans.
	I have identified significant genotype-by-diet interactions for weight gain and other metabolic phenotypes in Drosophila, indicating that some genetic lines are metabolically sensitive to their diet while others are not. To identify metabolites that vary across genotypes and diets I performed metabolomic profiling on a subset of these lines by Gas Chromotography-Mass Spectrometry. Through these metabolomic approaches I have identified dozens of metabolites that show significant variation with diet, genotype, and the interaction between diet and genotype. Presently, I am performing whole genome expression analyses and metabolomic profiling on a common set of samples to identify genes that are changing in expression in concert with diet and genotype, and the correlated response in metabolites.
Evolutionary Genetics of Speciation
	Ecological context is essential to understanding the evolution of genetic architecture. In my graduate work I used cactophilic Drosophila, a species endemic to the desert Southwest with an interesting ecology, to clarify the ecological history the species group based on population genetics and phylogenetics (Reed et al. 2007), and to address the fundamental evolutionary puzzle of the genetic basis of speciation. We found significant within-species genetic polymorphism for between-species postzygotic isolation (Reed and Markow, 2004). We mapped the genetic architecture of hybrid male sterility as it is manifested directly in the F1 hybrids (Reed et al., 2008). By discovering that hybrid male sterility is controlled by multiple contributing loci and epistatic interactions, we found that it is a complex trait before it becomes fixed in the incipient species. These findings indicate that postzygotic isolation is likely to evolve largely by the haphazard force of drift or, perhaps, balancing selection, allowing it to languish in a polymorphic state.
Contact: Dept. of Biological Sciences, Box 870344, Tuscaloosa AL 35487 phone: (205) 348-1345 email: lreed1 at bama.ua.edu

Laura K. Reed

My research interests lie at the intersection of quantitative genetics and population genetics, where I explore the evolution of complex traits such as metabolic disease that are the result of multiple genetic effects and the environment. Historically, there are two basic approaches to understanding biology. The first involves dirt-under-your-fingernails fieldwork to characterize systems in their ecological context where they display all of their fascinating natural genetic and environmental variation. And the second seeks a complete understanding of a few genetic systems, such as the OregonR strain of Drosophila melanogaster, in the tightly controlled environment of the laboratory. Both of these approaches are crucial to our accelerating understanding of how life works. The next major innovations are coming as these two approaches meld through the technological advances caught under the umbrella of systems biology. By unifying dirty and sterile biology through systems biology, I am trying to understand the genetic and environmental architecture of natural variation.

Mechanistic Origins of Natural Phenotyptic Variation

To understand disease, ultimately we have to understand each omics level, how it evolves, and the mechanisms by which it can be perturbed. Phenotypic variation derives not only from genetic variation but also from the environment that can introduce both predictable and random perturbation of the physiological system. Metabolic homeostasis is achieved through interactions between different physiological or omics levels within an organism, and by feedback into the evolutionary genetics of the species through fitness effects.

Metabolic Syndrome (MetS) is a constellation of symptoms such as obesity, elevated blood lipids, and insulin resistance that are predictive of type-2 diabetes and cardiovascular disease. MetS is a recently developed syndrome caused by our increased calorie intake and decreased exercise that exposes cryptic genetic variation: some people can eat high-fat, high-sugar diets without adverse impact while others are highly sensitive to their diet. My research explores these effects using Drosophila, which also harbor cryptic genetic variation for disease, as a model to characterize the architecture of genotype-by-environment interactions of human-like metabolic disorders. With this charismatic model organism, I gain all the advantages of a carefully dissected metabolic and genetic system with substantial metabolic similarity to humans, while also being able to sample natural variation with high throughput genomic methods. Thus, using Drosophila, I can gain insights into a genetically complex disease that affects humans.

I have identified significant genotype-by-diet interactions for weight gain and other metabolic phenotypes in Drosophila, indicating that some genetic lines are metabolically sensitive to their diet while others are not. To identify metabolites that vary across genotypes and diets I performed metabolomic profiling on a subset of these lines by Gas Chromotography-Mass Spectrometry. Through these metabolomic approaches I have identified dozens of metabolites that show significant variation with diet, genotype, and the interaction between diet and genotype. Presently, I am performing whole genome expression analyses and metabolomic profiling on a common set of samples to identify genes that are changing in expression in concert with diet and genotype, and the correlated response in metabolites.

Evolutionary Genetics of Speciation

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Ecological context is essential to understanding the evolution of genetic architecture. In my graduate work I used cactophilic Drosophila, a species endemic to the desert Southwest with an interesting ecology, to clarify the ecological history the species group based on population genetics and phylogenetics (Reed et al. 2007), and to address the fundamental evolutionary puzzle of the genetic basis of speciation. We found significant within-species genetic polymorphism for between-species postzygotic isolation (Reed and Markow, 2004). We mapped the genetic architecture of hybrid male sterility as it is manifested directly in the F1 hybrids (Reed et al., 2008). By discovering that hybrid male sterility is controlled by multiple contributing loci and epistatic interactions, we found that it is a complex trait before it becomes fixed in the incipient species. These findings indicate that postzygotic isolation is likely to evolve largely by the haphazard force of drift or, perhaps, balancing selection, allowing it to languish in a polymorphic state.

Contact: Dept. of Biological Sciences, Box 870344, Tuscaloosa AL 35487
phone: (205) 348-1345 email: lreed1 at bama.ua.edu