Research Projects Available at Harvey Mudd College 2015–2016

Computational studies to identify horizontal transfer events in bacteria

Advisor: Prof Bush

Our current area of focus is identifying horizontal transfer events in bacterial species. Horizontal transfer is the movement of DNA from one species or strain to another. It is a characteristic feature of bacterial evolution. Many approaches can be taken to identifying such events. These range from analyzing sequence composition to comparing closely related species. Our aim is to develop a method that brings these different approaches together to robustly identify horizontal transfer events.

Therapeutic Small RNA Delivery and Processing

Advisor: Prof. Haushalter

Students in the Haushalter lab design, construct, and evaluate vectors for delivering therapeutic small RNA molecules. A theme of recent projects has been building chimeric RNA molecules that combine one or more therapeutic modalities onto a tRNA template. For example, short hairpin RNAs targeted against HIV have be inserted into the 3′ trailing sequence of a pre-tRNA expressing construct and tested for their ability to knockdown target genes important for HIV replication. Interested students should contact Prof. Haushalter for additional information.

Feeding behavior control by intestinal stem/progenitor cells

Advisor: Prof. Hur

Aging and feeding are deeply interconnected. In essentially every model organism where it’s been tested, dietary restriction, the controlled and severe deprivation of nutrients to near-starvation levels, has been shown to be effective in increasing lifespan. Although this intervention has been known and studied for almost 80 years, many details of the mechanisms involved remain unresolved. Previous work exploring aging and feeding behavior in fruit flies have suggested that the intestinal stem cells may play a pivotal role in connecting diet and longevity. While progress has been continuous in examining the role of intestinal stem cells on lifespan, what role these cells may play in feeding behavior has not been as well characterized. As part of ongoing work in looking at the role of intestinal stem cells in aging in fruit flies, projects to tease apart the role of intestinal stem cells on feeding behavior are available.

Metabolic manipulations that influence aging

Advisor: Prof. Hur

As a vital, but typically harmful, process, mitochondrial metabolism is deeply interconnected with aging. Due to its central role in mitochondrial metabolism, Complex I of the electron transport chain is an attractive target for experimental manipulations to examine the effects of metabolic manipulations on lifespan. Unfortunately, Complex I is exceedingly complicated, being composed of more than 40 individual proteins that require careful step-wise assembly catalyzed by multiple assembly factors to form functional Complex I enzymes. Previous studies have resulted in seemingly contradictory results that suggest that both reduced and increased Complex I function are sufficient to extend lifespan. Project are available to try to resolve this apparent paradox.

Role of Protein Homeostatic Mechanisms in Aging

Advisor: Prof. Hur

Though protein homeostasis or “proteostasis” mechanisms that mediate protein quality control in cells have been known for a long time, their specific role in aging have not been a focus of aging research until relatively recently. It’s been shown that as organisms age, their ability to maintain a functional proteome declines. In addition to contributing to the formation of protein aggregates that are implicated in the etiology of important degenerative diseases such as Alzheimer’s disease and Huntington’s disease, decline in proteostasis has been suggested to be a major cause of general aging associated decline. Protein degradation pathways are well characterized in flies and many targets are available. Previous results from the lab have suggested that tissue-specific over-expression of some genes involved in proteostasis can increase lifespan. What the physiological and biochemical implications of these manipulations are, and how they may extend lifespan are available for study.

Regulatory sequences that determine quantitative control of transcriptional output

Advisor: Prof. Stoebel

Molecular geneticists have spent over forty years understanding how specific DNA sequences and the proteins that bind to them can dicate patterns of transcription. This work has produced detailed understanding of the kinds of proteins that play these roles and the phenotypes that are regulated by transcription, we almost always lack a quantitative description of this process. How does the amount of a regulatory protein influence the amount of transcription from a given gene?

Our lab has identified genes in E. coli that respond differently to the amount of RpoS in the cell. Some of these genes reach maximal levels of transcription with low levels of RpoS, while others require high levels of RpoS. This project will use cloning, site-directed mutagenesis, and reporter gene assays to locate the sequence or sequences that determine these patterns of transcription. This project will help us better understand how shifting concentrations of regulatory proteins change the transcriptome and influence phenotype.

Bioinformatic analysis of the horizontally acquisition of a global regulatory protein

Advisor: Prof. Stoebel

Bacteria can rapidly evolve new phenotypes by horizontal gene acquisition: the gain of DNA from an unrelated species. Perhaps the most radical of these changes are the gain of new global regulatory proteins, which can alter the pattern of expression of many genes in a single step. One such horizontally acquired protein is Hfp, which appears to have been gained in a number of strains of E. coli and its relatives. This project will use whole-genome sequences to reconstruct the pattern of horizontal gain, the location the gene has been inserted into the genome, and the mobile element that brought the gene into the genome.

Scaling in social insect colonies

Advisor: Prof. Donaldson-Matasci

Social insects live in colonies of various sizes. Bumble bee colonies, for example, generally consist of hundreds of bees, while honey bee colonies consist of tens of thousands. Across the social insects, these differences in colony size tend to be associated with differences in behavioral complexity. For example, bumble bees can indicate to nest mates that they have found a rewarding food resource. Honey bees take it one step further, using their famous “dance language” to communicate not only about the existence of resources, but also about their location and quality. How does foraging efficiency scale with colony size, and how does this depend on communication? What role does the environment play?

To explore these questions, we would like to quantify how various aspects of social insect foraging depend on the interaction between colony size, communication, and environment. This project would involve some combination of: (1) mathematical modeling of honey bee and/or bumble bee foraging, (2) computer simulations of honey bee and/or bumble bee foraging, and (3) data analysis of experiments with honey bees foraging in the field.

The function of diversity within social groups

Advisor: Prof. Donaldson-Matasci

In most social insect colonies, the workers are all full sisters: offspring of a single queen mated with just one male. This close relatedness between individuals is thought to reduce conflict and promote the evolution of cooperative behaviors. However, in honey bees, queens mate with multiple males, producing 10-20 different patrilines (groups of individuals sharing a father) within a single colony. Why is this? What advantage might genetic diversity within a colony have, that could outweigh the potential for within-colony conflict? Studies have shown that honey bee colonies with multiply mated queens are healthier, more active, and forage more effectively than those with singly mated queens. However, the reasons for this are still not understood. One idea is that genetic diversity underlies the division of labor, so colonies with multiply mated queens might be able to balance work across tasks more effectively.

To explore this idea, this project would involve constructing a mathematical model of genetic diversity and division of labor within a honey bee colony and/or simulations of colonies in different environments. Is genetic diversity particularly useful in certain kinds of environments, or does it provide flexibility and robustness across many environments? This project could potentially also involve analysis of data from previous experiments on honey bee colonies with singly and multiply mated queens.

Matrix Models of Lizard Populations

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 computer models of lizard populations using published life history data.

Lizard Locomotion

Advisor: Prof. Adolph

Lizards experience a variety of temperatures and habitat structures in their natural environments. This laboratory project will measure lizard locomotor performance across different conditions (e.g., temperature, slope), and how performance varies with body size.

Lizard Metabolism

Advisor: Prof. Adolph

Night lizards (Xantusia) are known to have low metabolic rates. This project will quantify how body size and temperature affect metabolic rate. We will also measure temperatures in the desert microhabitats of night lizards, and combine these data with metabolism measurements to calculate total energy budgets.

Characterization of mitochondrial genome evolution in octocorals with compromised DNA repair mechanisms

Advisor: Prof. McFadden

Unlike almost all other metazoan animals, the mitochondrial genomes of octocorals (soft corals and sea fans) evolve at rates that are slower than those of the nuclear genome. One hypothesis for this difference is the presence in the octocoral mt genome of mtMutS, a gene that codes for a DNA mismatch repair protein. This gene evolves rapidly by a process that includes many insertions and deletions of amino acids; as a result, the mtMutS genes of different octocoral genera and families differ greatly in protein sequence and presumably also in function and efficiency. We have identified a genus of octocorals in which the mtMutS gene appears to be non-functional. Species in this genus exhibit much higher rates of mitochondrial gene evolution than other octocorals, as well as novel mt genome rearrangements. The goal of this project is to sequence the complete mt genomes of several of the species in this fast-evolving group, using next-generation sequencing protocols to sequence a large number of mt genomes simultaneously. By quantifying their rates of gene evolution and genome rearrangement in comparison to other genera with “normal” slow rates of mt genome evolution we hope to elucidate further the role of mtMutS in DNA repair in the octocoral mitochondrion.

Delimitation of species boundaries in the soft coral genus Sinularia

Advisor: Prof. McFadden

Members of the soft coral genus Sinularia are ecologically dominant space-occupiers on Indo-Pacific coral reefs. Recent coral bleaching events associated with climate change have resulted in high rates of mortality of Sinularia, a long-lived species that recovers very slowly from such disturbance. Study of the ecological impacts of these mortality events is hampered by a lack of understanding of species boundaries in the genus, and an inability to distinguish species reliably. Often there is no concordance between observed morphological vs. genetic differences among individuals: in some cases genetically distinct specimens cannot be distinguished morphologically, while in others morphologically distinct specimens cannot be distinguished using standard genetic markers. This project will explore the use of RADseq (restriction-site-associated DNA), a next-generation sequencing methodology, to better resolve species boundaries in Sinularia. RADseq generates millions of sequence reads from a subset of the genome of each individual that can then be screened bioinformatically to identify single-nucleotide polymorphisms (SNPs). Patterns of shared SNPs across many loci allow species to be discriminated from one another. We will use this method to test if species of Sinularia that have been described based on morphological differences are indeed reproductively isolated from one another. This project requires both laboratory and computational work.

Regulation of plant stem cell proliferation

Prof: Xuelin Wu

Research in my lab focuses on the mechanisms controlling cell cycle activation and tissue proliferation in response to both developmental and nutritional cues. We use Arabidopsis thaliana as a tractable, easily manipulated model system, to answer the following questions: (1) what are the mechanisms by which developmental cues regulate meristem cell cycle activation? (2) How does carbon source availability regulate cell division activities? (3) How are these two aspects of regulation integrated at the level of cellular activities? Come by for a chat if you are interested in finding out the details about potential projects.

Neural Control and Biomechanics of Human Walking: Toe- vs Heel-Runners

Advisor: Prof. Ahn

Humans use two motor control patterns in their lower limb muscles during walking. Half the population (MG-biased) walks while activating their medial calf muscle (MG) much more strongly than their lateral calf muscle (LG). The other half of the population walks while activating both calf muscle equally (unbiased). An MG-biased motor control pattern always correlates with MG muscles. In sedentary walkers, an MG-biased motor control pattern correlates with shorter muscle moment arms (heel length) and increased variability in plantar pressures on the medial side of the foot. In recreational runners, however, an MG-biased motor control pattern correlates with longer muscle moment arms. The senior research student will examine whether toe-runners and heel-runners show similar muscle activity and biomechanics or whether the different styles of running correlates with differing neural control and biomechanics during the seemingly simple behavior of walking.

Effect of Temperature on Hemolymph Viscosity of Tarantulas

Advisors: Prof. Ahn & Prof. Adolph

Tarantulas locomote using an elaborate hydraulic system. Not only do they lack extensor muscles in 2 joints in each of their 8 legs, but they also they maintain very high internal pressures. By compressing their body segments, they push hemolymph (blood) into their limbs, which further increases the internal pressure and extends the jointed limb segments. Despite the seemingly coarse hydraulic system, tarantula behaviors can range from incredibly fine motor during web-weaving to sprinting, pouncing on, and capturing prey. This project will measure and quantify the hemolymph viscosity at a range of ecologically relevant temperatures (15 to 40°C).