The alternative sigma factor RpoS is a global regulatory protein in E. coli. RpoS regulates the expression of over 10% of the genome in order to respond to stresses like starvation, low temperature, or high osmolarity. Naturally occurring strains of E. coli are thought to vary extensively in the amount of RpoS protein they express, but little is known about the transcriptomic and physiological consequences of this variation.

Multiple projects are available in the lab, including: exploring how naturally occurring strains vary in their levels of RpoS expression across different environments; determining the effect of variation in RpoS levels on resistance to a variety of stresses; using genome sequences to make predictions about the evolution of stress resistance which can then be tested using molecular genetic techniques; measuring the effects of variation in stress resistance on the transcriptome using microarrays and other molecular genetic techniques; and exploring how horizontally acquired genes become integrated into the pre-existing regulatory networks of bacteria.

Other molecular and evolutionary genetic projects may be available: I encourage interested students to speak with me about their interests.

Computational biology projects in the Bush lab
Advisor: Prof. Bush
Our general interest is in using computational approaches to study evolution. This includes traditional sequence analysis based computational biology projects, and also theoretical projects that involve modeling molecular processes or evolution.

One ongoing interest in the lab is in understanding the evolution of enzyme cooperativity. Most enzymes operate in multi-subunit complexes, with multiple identical or nearly identical enzymatic subunits bound together. One purpose of such complexes is to allow for allosteric cooperativity. By allosteric cooperativity we mean that the binding of one enzyme subunit to its ligand can influence the affinity of other subunits for that ligand. Such influence has the global effect of altering the shape of the ligand binding curve. The central goal of this project is to understand why cooperativity in metabolic enzymes evolves. To address this problem we are developing an artificial life system which allows us to study the evolution of allosteric cooperativity. The advantage of such a system is that it allows us to strip away biochemical complexity and focus on the evolutionarily consequences of cooperativity.

We also have a  collaborative project with Prof Stoebel's lab which focuses on horizontal transfer in Escherichia coli. Horizontal transfer, the movement of DNA from one strain/species to another, is an important process in bacterial evolution. The goal of this project is to better understand how the expression of horizontally acquired genes evolves. The computational component of the project will focus on the molecular evolution of regulatory elements for horizontally transferred genes.

 

Evaporative water loss in lizards
Advisor: Prof. Adolph
Reptile skins are highly resistant to water loss, but not completely.  This laboratory project will examine evaporative water loss in several species of spiny lizards (genus Sceloporus).  In particular, we will examine how water loss is affected by lizard body size and by scale size.  These two phenotypic traits vary across Sceloporus species, and several comparative studies have found that body size and scale size are correlated with climate variables including temperature and aridity.  These correlations suggest a functional relationship between these traits and water loss.

 

Metapopulation models of lichen ecology
Advisor: Prof. Adolph
Organisms that live on plants (epiphytes) have temporary habitats and therefore must be able to recolonize new habitats to persist.  Mathematical models of recolonization and extinction can help to identify the important factors that affect a species' ability to persist.  This project will extend a current metapopulation model to multiple species living in a dynamic environments in which habitat patches are lost due to disturbances such as wildfires.  This approach is particularly applicable to lichens that inhabit living plants or dead wood substrates.

Matrix models of lizard population dynamics
Advisor: Prof. Adolph
Many field studies have determined how survival and reproductive rates of lizards vary with age. These data can be used to construct matrix models of population dynamics, which in turn can be used to explore interesting ecological, conservation and evolutionary questions.  This project will involve building and analyzing population models using published life history data.

Advisor: Prof. Haushalter (Biology and Chemistry)
The long-range goal of this project is to develop a gene therapy approach to treating HIV-AIDS.  As an intermediate goal, students in the Haushalter lab will synthesize and characterize variants of a tRNA-shRNA chimera molecule that can be introduced into target cells and has been designed to knockdown CCR5 expression.  CCR5 is the co-receptor that R5-tropic HIV viruses use to gain access to target cells.  Students will work on optimizing the sequence of the tRNA-shRNA construct and characterize their product by examining the downstream activity of the short-hairpin RNA, as measured by dual-luciferase functional assays.  

Evolution of cis regulatory modules in Drosophila

At the Drosophila melanogaster bithorax complex (BX-C) over 330kb of intergenic DNA is responsible for directing the transcription of just three homeotic (Hox) genes during embryonic development.  A number of distinct enhancer cis-regulatory modules (CRMs) are responsible for controlling the specific expression patterns of the Hox genes in the BX-C.  While it is has proven possible to identify orthologs of known BX-C CRMs in different Drosophila species using overall sequence conservation, this approach has not proven sufficiently effective for identifying novel CRMs or defining the key functional sequences within enhancer CRMs.  The major focus of this study is to investigate if the spatial clustering of transcription factor binding sites is critical for BX-C enhancer functional activity.  Utilizing a combination of computational, genetic and molecular approaches the goal will be to analyze the regulatory architecture at least two independent BX-C enhancers through molecular dissection and evolutionary comparison across the Drosophila genus.

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In humans, the enzyme telomerase (hTERT) is responsible for the synthesis of new repeat sequences at the telomeres of chromosomes.  Although active in early embryogenesis, the hTERT gene is transcriptionally silenced in almost all somatic cells in the adult, but is aberrantly re-activated in over 90% of human cancers.  The molecular mechanisms responsible for repression of this gene are thought to involve the transcription factor CTCF.  The aim of this study is to determine the functional importance of bioinformatically identify CTCF binding sites in the hTERT proximal exonic region (PER) using a reporter gene assay in HeLa cancer cells.

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