Research Projects Available at HMC 2014–2015

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.

Role of gut stem/progenitor cell metabolism on feeding behavior and lifespan

Advisor: Prof Hur

Aging is an almost universal biological phenomenon that results in increased physiological decline, susceptibility to most major diseases, and ultimately, death. My lab aims to study aging as a biological phenotype in order to understand how it occurs and whether it’s possible to delay it or ameliorate its effects.

Feeding behavior has been known to be intimately related to longevity for almost 100 years now. Specifically, dietary restriction regimes which reduce feeding to a point just short of starvation have been shown to significantly extend lifespans in a variety of model organisms. In a recent set of experiments, it’s been demonstrated that altering feeding behavior can have dramatic effects on the physiology of guts and stem/progenitor cells that populate the gut in fruit flies. Therefore, a complex interconnected relationship exists among gut stem/progenitor cells, gut physiology, feeding behavior, and lifespan in flies. In a previous study, we have shown that expression of a transgene that should increase metabolic output in fly gut stem/progenitor cells can alter gut physiology and increase feeding behavior, suggesting that one way in which dietary restriction may increase lifespan is by altering gut physiology. A library of transgenic constructs that can directly affect metabolism is available in flies (mostly by RNAi knock down of electron transport genes), and by using a gut stem/progenitor cell specific expression system, we can begin to see what effects altered metabolism in gut stem/progenitor cells may have on feeding behavior and ultimately on lifespan. If this sounds interesting, please come by for a chat!

Electron Transport Chain Complex I and Aging

Advisor: Prof Hur

We have characterized a gene that is involved in the assembly of complex I of the fruit fly electron transport chain. This is an exceedingly complicated holoenzyme composed of more than 40 individual proteins, some encoded by mitochondrial DNA, some nuclear in origin, that are assembled into one functioning unit. Surprisingly, decreasing function of this assembly gene in the fruit fly gut appears to be sufficient to significantly increase lifespan. Multiple different pathways are reasonably expected to be involved in this lifespan extension, and the project will involve checking their interactions to puzzle out what is occurring to extend lifespans in these flies.

Role of Protein Homeostatic Mechanisms in Aging

Advisor: Prof Hur

Though protein homeostasis or “proteostasis” mechanisms which 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. The project will involve checking whether the expression of specific genes can boost proteostasis during aging, to see if this boost is sufficient to delay aging, and finally to examine the physiology associated with increased proteostasis.

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.

Neural Control of Tarantula Locomotion

Advisor: Prof. Ahn

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 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 recruitment patterns of the muscles controlling hydraulic extension mechanism of their legs while running at different speeds.

Communication and foraging in social groups

Advisor: Prof. Donaldson-Matasci

Honey bees use their famous “dance language” to communicate about the location of rewarding food sources (flowers). In contrast, bumblebees communicate that they have found resources, but not about their location. Why do honey bees dance, while bumblebees do not? One possibility is that because bees spend more time dancing for high-quality flowers, more individuals are recruited to those resources. Those bees in turn may recruit more foragers, leading to a gradual buildup of foragers at better resources. This process may allow the colony as a whole to forage more efficiently, by concentrating more foraging effort on better resources, while still remaining flexible enough to shift that effort when resource quality changes. Second, it may also allow the group to search the area more efficiently, by dividing up the search effort among many individuals and sharing information about resources when they are found.

To test these hypotheses, we would like to quantify the dynamics of honey bee foraging with and without dance communication. This project would involve some combination of: (1) mathematical modeling of honey bee and bumblebee foraging, (2) computer simulations of honey bee and bumblebee foraging, and possibly (3) experiments with captive bumble bee colonies in the lab.

The function of diversity within social groups

Advisor: Prof. Donaldson-Matasci

Unlike other social bees, bumble bees show incredible variation in body size, even among workers within the same colony. Why? One possibility is that different sized bees are best suited for different tasks, e.g. the larger bees are better foragers, while the smaller bees require less energy and are thus more efficient at other tasks like raising brood. Another possibility is that larger bees are better in times of plenty, while smaller bees are better when resources are scarce‚ and in an unpredictable environment it is better to have some of both.

To explore these possibilities, this project would involve constructing a mathematical model of the energy balance of a bumble bee colony, supplemented by simulations of colonies in different environments. In what sorts of environments is variation in body size most useful, and perhaps most likely to evolve? This project could potentially also involve experiments with captive bumble bee colonies in the lab.

Decentralized defense strategies (or, how ants play the game of Risk)

Advisor: Prof. Donaldson-Matasci

Turtle ants are named for their heavily armored soldiers, which defend the nest against potential intruders. Since each colony inhabits multiple nests, the colony must somehow divide multiple soldiers among multiple nests, some of which may be more valuable or easier to defend than others. Furthermore, because there is no central decision-maker for the colony (no “general” directing the troops) the strategy the colony uses must be an emergent consequence of fairly simple decision-making rules used by individual soldiers. What kind of rules might these soldiers use to decide which nest to defend, and how much information do individuals need? Can such rules produce an optimal defensive strategy for the colony as a whole?

This project will explore these questions using simulation models of ant colony defense. Depending on availability of turtle ant colonies, it could also involve laboratory experiments.

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.

The Role of the Global Regulatory Protein RpoS in Shaping the Transcriptome

Advisor: Prof. Stoebel

Bacteria regulate the transcription of their genome in response to to their external environment. Global regulatory proteins shape these patterns of transcription, regulating hundreds or thousands of genes. Of particular interest to my lab is the protein RpoS, which many of the genes in the E. coli genome in response to stresses like starvation, low temperature, or high osmolarity. Different sets of genes are regulated by RpoS under these conditions. How can one protein regulate different sets of genes under different conditions?

One clue comes from the observation that the amount of RpoS that cells produce varies from stress to stress. We aim to test the hypothesis that genes respond differently to the concentration of RpoS in the cell.

Projects are available that test this hypothesis using a variety of approaches. Depending on your interests and skills, you might analyze existing RNA-seq data (and potentially generate more) to define the entire RpoS regulon; build and use a system to measure how individual promoters respond to variation in the amount of RpoS produced by cells; and create synthetic promoters and specific mutants to understand rules for why some promoters are more sensitive than others to levels of RpoS. Other approaches and projects may be available for students with specific interests. If this sounds like fun, come talk!

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.