Biology Research Opportunities at the Claremont Colleges

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Summer 2013

The 5C SURP has a number of summer research positions available. Most of these are funded by our collaborative grant from the Howard Hughes Medical Institute (HHMI). Students from any college can apply for any of the listed positions. Applications for these summer positions are due February 19 (see link below to download the application).

All Biology Summer Research Students are expected to work full-time for 10 weeks during the summer. The exact starting and ending dates are stipulated by the faculty advisor. Depending on the source of funding, students may also be required to participate in other activities, such as weekly seminars by guest speakers. Stipends for 2013 summer research students are expected to be approximately $5,000.

Application Process

1. Download the application form (pdf).

2. Look at the list of available projects and advisors, and talk to the relevant faculty mentor(s) about the project(s) that interest you.

3. Turn in an electronic copy of your research application to the Biology office at Harvey Mudd College (biology@hmc.edu) by Tuesday, February 19, 2013. We will try to notify students about positions by Friday, March 8th.

Available Projects

Available projects for summer 2013 are listed below.

Please contact Prof. Drewell (drewell@g.hmc.edu) if you have additional questions.

Projects available for Summer 2013 from the Claremont Colleges:

KECK JOINT SCIENCE DEPARTMENT

Ecology and Evolution (KSD)

Project 1 (1-2 students):
Advisor: Prof. Sarah Gilman (sgilman@kecksci.claremont.edu)

My lab studies the organisms and communities of rocky intertidal shores, one of the most dynamic habitats on the planet. Intertidal shores alternate between terrestrial conditions, during low tide and marine conditions, when submerged at high tide. Each of these environments provides its own set of challenges to the organisms that inhabit it. Chief among these is temperature. Most intertidal species are ectotherms, meaning the temperature of the environment around them influences their body temperatures. Animals may be 10-12 °C when underwater, but warm to 35 °C at low tide. The great variance in thermal environments makes this a particularly interesting system for studying the consequences of warming due to climate change. This project involves using dynamic energy budget models to calculate an organism's growth and reproduction rates from basic information about how energy use changes with body size and temperature. We are in the process of developing such a model for the intertidal barnacle Balanus glandula, based on laboratory data we are currently collecting on the barnacle's physiology. A student involved in this project would help develop and test the model.

Skills/background required. Prior programming experience, preferably in Matlab. A familiarity with basic concepts in ecology and physiology will be helpful. This project could include field work.

Project 2 (1-2 students):
Advisor: Prof. Sarah Gilman (sgilman@kecksci.claremont.edu)

My lab studies the organisms and communities of rocky intertidal shores, one of the most dynamic habitats on the planet. Intertidal shores alternate between terrestrial conditions, during low tide and marine conditions, when submerged at high tide. Each of these environments provides its own set of challenges to the organisms that inhabit it. Chief among these is temperature. Most intertidal species are ectotherms, meaning the temperature of the environment around them influences their body temperatures. Animals may be 10-12 °C when underwater, but warm to 35 °C at low tide. The great variance in thermal environments makes this a particularly interesting system for studying the consequences of warming due to climate change. This project involves developing models to predict how an organism will respond to climate change and understand how climate change will alter the organism's body temperature. Most intertidal species are ectotherms, meaning their body temperatures are influenced by their surrounding environment. Heat fluxes between the organism and its environment include solar radiation, conduction to ground and air, evaporative cooling, and air convection. These processes can be modeled by some fairly simple mathematical equations. We have been working on such a model for oysters and would like to expand it to barnacles.

Skills/background required. Prior programming experience, preferably Matlab or C. A prior course in physics that covers heat transfer would be helpful. This project could include field work.

Project 3 (1-2 students):
Advisor: Prof. Diane Thomson (dthomson@kecksi.claremont.edu)

My lab uses population models combined with field data to predict and understand the outcomes of interactions between native and invasive species and the effects of climate change on extinction risk, particularly for plants. We have several ongoing projects with a modeling component. This project involves a study of the invasive species which are now dominant in almost all grassland habitats within California. One mechanism that may explain this pattern is their early germination relative to most native annuals, which allows them to stake out access to resources before competitors emerge. We are interested in two main questions: 1) Are native annuals under selection to evolve earlier germination timing because of this competition with invasives, and 2) How do the costs and benefits of early germination depend on climate? This project would involve making simple population models to compare the fitness/growth rates of early vs. late native annual germinators under different competition/climate scenarios.

Skills/background required: A familiarity with simple population models and some experience with programming in Matlab or R.

Project 4 (1-2 students):
Advisor: Prof. Diane Thomson (dthomson@kecksi.claremont.edu)

My lab uses population models combined with field data to predict and understand the outcomes of interactions between native and invasive species and the effects of climate change on extinction risk, particularly for plants. We have several ongoing projects with a modeling component. This project an investigation of the effects of Introduced herbivores and climate change on the high endemic biodiversity on islands. In collaboration with the National Park Service/USGS, we have been collecting and analyzing monitoring data on a number of rare and endemic plants before and after introduced herbivore removal, and over a number of years with different climate conditions. We are using these data to build stage structured matrix models that explore the extinction risk of these rare plants under different climate/herbivory scenarios.

Skills/background required: A familiarity with basic population models (experience with matrix/stage structured models is especially helpful) and some previous programming in Matlab or R. Some background in statistics is also important.

Project 5 (preferably 2 students):
Advisor: Lars Schmitz (lschmitz@kecksci.claremont.edu)

The foremost goal of the research in my lab is to achieve a better understanding of the origins of diversity. We describe and analyze macroevolutionary diversity patterns with an integrative approach, combining phylogenetic inferences from living organisms with paleontological data across large temporal scales. We collect data on multiple levels, including morphological, functional, and ecological diversity of major vertebrate radiations. Data collection and analysis is guided by predictions from functional morphology within the context of major evolutionary transitions in vertebrate history that come with enormous physical challenges and different performance requirements. The main study system of the lab is the vertebrate eye. This project involves an investigation of the tempo and mode in the morphological evolution of functional systems in birds: We will examine the rate of morphological evolution across different functional systems across a large sample (>100 species) of living and fossil birds. The functional systems will include the eyes, jaws, and locomotory apparatus, and we will use the data to answer the question whether different functional systems evolve with different tempo and mode. One part of the project involves data collection on museum specimens; the other part is focused on multivariate statistics and phylogenetic comparative methods using state-of-the art phylogenies. Phylogenetic comparative methods will include, for example, the assessment of phylogenetic signal, the fitting of evolutionary models (Brownian motion, OU), and phylogenetic measures of disparity.

Skills/backgrounds required: This project ideally involves two students, one who has a stronger background in quantitative methods (mathematics, computer science, physics) and another with stronger preparation in laboratory research (biology, chemistry, neuroscience).

Molecular biology (KSD)

Project 6 (1-2 students):
Advisor: Prof. Jennifer Armstrong (jarmstrong@kecksci.claremont.edu)

armstronglarvae Fluorescently labeled antibodies to investigate binding of chromatin-associated proteins on polytene chromosomes from salivary glands of third instar Drosophila larvae (see Figure). One limitation of this technique is that it is inherently qualitative. Liana Engie (Pitzer 2011) wrote a Matlab program with a graphic user interface (GUI) that allows us to quantify immunofluorescence from polytene chromosomes while creating a mask over the chromosomes to easily subtract any background signal. Liana validated her program by comparing pixel sums to the Intensity Analysis function in Image Pro and her program yielded pixels sums identical to six significant digits. The instructions for this program as well as the Matlab code are available on my website: http://faculty.jsd.claremont.edu/jarmstrong/fquant/index.html. I am looking for a student who can re-write the Matlab code such that the program can be run on a suitable freeware program. I would also like the program further validated by comparing it to Volocity 3D Image Analysis Software.

Skills/background required: Experience with programming in Matlab as well as in freeware programs is essential. The student must be quite independent, as I am not a programmer.

Project 7 (1-2 students):
Advisor: Prof. Scott Gould (sgould@kecksci.claremont.edu)

DNA nanotechnology holds tremendous promise for both science and technology, offering unprecedented control over structure and function at the nanoscale (http://web.physics.ucsb.edu/~deborah/). For science, it offers model systems for testing our understanding of biology’s amazing macromolecular self-assembly and reaction dynamics. For technology, it offers platforms for patterning materials and building devices that respond to biological signals. However, present day development of DNA nanotechnology is hampered by the low throughput of techniques (AFM, EM, electrophoresis) used to evaluate the yield and quality of designed structures. To devise higher-throughput measures, we are focusing on DNA nanotubes, structural primitives that can grow to micrometer lengths and are thus accessible by light microscopy.

This summer project will contribute to our collaboration with the group of Prof. Luke Theogarajan that aims to develop a technique for assessing the distribution of lengths and widths of DNA nanotubes by monitoring the changes in electrical current as individual nanotubes pass through a nanopore. We hypothesize that the magnitude of a current fluctuation measures the diameter of the nanotube and that the duration of the fluctuation measures its length. To test these hypotheses the summer intern(s) will fabricate DNA nanotubes of defined circumference, measure their length distributions at a variety of temperatures and concentrations using fluorescence microscopy and look for correlations with nanopore conductance data. This project involves collaboration with Prof. Deborah Fygenson at UC Santa Barbara.

Skills/background required: 1 year of intro bio, intro chemistry and intro physics.

Project 8 (1-2 students):
Advisor: Prof. Paul Nerenberg (pnerenberg@kecksci.claremont.edu)

The most prevalent of all post-translational modifications is glycosylation, the covalent attachment of a carbohydrate, which is thought to occur on over 50% of proteins in eukaryotes. These carbohydrates are most commonly linked to the asparagine residues of proteins in a process known as N-linked glycosylation. One unknown aspect of this process is the role of the target protein’s conformation in the final step of the reaction – the transfer of the carbohydrate from its carrier protein (oligosaccharyltransferase) to the target protein. Using MD simulations, we would compare the conformational preferences of different glycosylation sequence peptides to determine which, if any, of these preferences might explain previously obtained experimental data regarding the varying glycosylation efficiency of these sequences. These data will help to elucidate the final step in this ubiquitous modification mechanism and could form the basis of a (physics-based) bioinformatics tool to predict N-linked glycosylation sites in proteins.

Skills/Background: Students interested in this project should have completed the introductory course sequences in chemistry, physics, and biology

Project 9 (1-2 students):
Advisor: Prof. Irene Tang (ztang@kecksci.claremont.edu)

This project involves a comparative genomic study of the genetic networks for environmental stress response in the evolutionary context of budding yeast Saccharomyces cerevisiae and fission yeast Schizosaccharomyces pombe, in collaboration with my colleagues in chemistry, engineering, and biology on different campuses of Claremont Colleges. The chosen phenol derivatives are naturally occurring and synthetic compounds that serve various roles in plant life and exert effects on other eukaryotes as environmental stress factors, influencing species diversity in ecosystems. Living organisms maintain homeostasis and are robust to perturbations including mutations and environmental variations to gain selective advantage for survival. Not all gene products are equal in ensuring the phenotypic stability of organisms that are constantly exposed to genetic and non-genetic perturbations. The questions are: What genes encode phenotypic stabilizers that contribute to robustness of organisms to environmental changes in the presence of different stress factors? What are the phenotypic stabilizers required for a specific stress or general responses to environmental changes, respectively? What components of the response networks are conserved through evolution? Are DNA checkpoint/repair, cell cycle control, and ER-stress signaling critical for cellular survival of environmental stress? Genomic analysis, data mining, data digitalization and quantification are used to construct profiles of gene response networks for environmental stress.

Skills/background required: Students with molecular/cellular biology background, as well as students with engineering/computer science background and computer programming skills.

Project 10 (1-2 students):
Advisor: Prof. Irene Tang (ztang@kecksci.claremont.edu)

This project is related to Project 9. My lab also works on the genomic sensitivity profiles in fission yeast for different platinum-based anticancer drugs including cisplatin. One main goal of the project is to identify genes responsible for the sensitivity and resistance to various platinum-based drugs, in order to understand more about the targets of these drugs and the mechanisms of their action. Similar genomic and quantification approaches are used as the first project listed above.

Skills/background required: Students with molecular/cellular biology background, as well as students with engineering/computer science background and computer programming skills.

Project 11 (1-2 students):
Advisor: Prof. Brian Thines (bthines@kecksci.claremont.edu)

Plants, being sessile, cannot escape their surroundings and must mount a molecular response to survive adverse environmental conditions. Plant cells alter gene expression programs and selectively remove certain proteins from the cell in these molecular responses. F-box proteins confer specificity to this protein removal by marking targets for degradation. Astoundingly, the Arabidopsis contains over 700 F-box genes, which is an enrichment that appears largely limited to plant genomes. We aim to understand why plant genomes have such a high number of F-box genes and to investigate specific biological roles for these. We have begun mining nearly 150 publically available microarray datasets representing gene expression levels in response to numerous biotic and abiotic stresses, as well as other chemical treatments. This project involves students on using hierarchical clustering across multiple stresses and time points to identify F-box gene expression patterns suggestive of specific biological roles. Students will also use these datasets to identify co-expressed genes that may help determine biological processes in which associated F-box genes act. Although we seek to understand the broader spectrum of expression patterns that this gene family adopts across all environmental conditions, we also aim identify candidates to further characterize in the context of specific stresses. This project contains an extensive bioinformatics component, but will also require validation of candidate genes under specific stress conditions with quantitative polymerase chain reaction (qPCR).

Skills/backgrounds required: Some background in statistics and molecular biology is required and some previous experience with R is helpful, but not required.

Project 12 (1-2 students):
Advisor: Prof. Babak Sanii (bsanii@kecksci.claremont.edu)

Many proteins associated with cell membranes depend on their local lipid environment to function properly. For example, the amount of cholesterol in the membrane can mediate a mismatch between the thickness of the membrane and the thickness of the protein. Similarly, there is often a “sweet spot” in the concentration of receptors in the membrane for protein-adhesion. If we could create an in vitro gradient of membrane compositions we could readily determine these protein-lipid interactions. This project aims to use the self-spreading and self-healing properties of lipid membranes to create such gradients of lipid compositions.

The students on this project will learn the wet-lab techniques of lipid physical chemistry, to produce self-spreading membranes that collide, self-heal and mix by diffusion. The mixing is modeled by two-dimensional diffusion, and the diffusion coefficient of the membrane is measured using a fluorescence imaging technique where the dye in a region is photobleached, and the diffusion of fresh dye into that region is measured as a function of time. Fourier analysis is used on these images to determine the diffusion coefficient. Once we quantitatively characterize the spreading and diffusion of the gradient, we will apply this new system to determine the ideal protein-adhesion environments of protein-lipid interactions (e.g., inactivated-cholera and GM1 lipids).

Skills/background required: Calculus, basic optical microscopy, safe lab habits, and a willingness to learn and collaborate.

Neurobiology (KSD)

Project 13 (1 student):
Advisor: John Milton (jmilton@jsd.claremont.edu or jmilton@kecksci.claremont.edu)

My laboratory focuses on the role that time delays play in shaping the behaviors of the nervous system. Applications range from postural stability to pursuit-escape tasks such as stick balancing at the fingertip to the prediction and generation of epileptic seizures. This project involves examining the role played by cutaneous mechanoreceptors for the control of stick balancing at the fingertip. The dynamics of an inverted pendulum are usually considered to be independent of the mass of the pendulum. However, it is observed for stick balancing by human subjects that for a given stick length, heavier sticks are more difficult to balance than lighter ones. It is possible that these observations arise because the heavier mass saturates the cutaneous mechanoreceptors at the fingertip and hence important sensory feedback for balance control is diminished and/or lost. This hypothesis will be tested in the context of a recent model developed for stick balancing that features the role of acceleration feedback for balance control (note that mechanoreceptors measure force and Newton says that F=ma). This project will involve both high speed motion capture studies of human stick balancing, computer simulations and comparisons between prediction and observation.

Skills/backgrounds required: The more quantitatively trained student should some background in computer programming and differential equations. The more experimentally trained student should have a background in biology and neuroscience and some computer programming skills. In particular they should be interested in learning how to run a high speed motion capture system.

Project 14 (1-2 students):
Advisor: John Milton (jmilton@jsd.claremont.edu or jmilton@kecksci.claremont.edu)

My laboratory focuses on the role that time delays play in shaping the behaviors of the nervous system. Applications range from postural stability to pursuit-escape tasks such as stick balancing at the fingertip to the prediction and generation of epileptic seizures. This project involves the development of a computer model for a neural network to investigate the dynamics of moderate scale neural networks: effect of time delay on synchronization. The synchronization of the activity of large populations of neurons lies at the basis for the generation of an epileptic seizure. Surprisingly it is controversial whether synchronization is more dependent on excitatory or inhibitory connections. Indeed studies of the properties of networks of simple neurons (e.g. integrate-and-fire) emphasize the role of excitatory connections when time delays are small and inhibitory connections when time delays are appreciable. It is not known whether the same observations arise when model networks are composed of physiologically reasonable models of neurons and neural connection topologies. The first goal of this project is to study the dynamics of a moderate scale (up to 3000 neurons) neural network using the NeuroSim/Skuld package developed by Syd Visser (University of Twente: http://wwwhome.math.utwente.nl/~visser/). The second step is to investigate the conditions for synchronization to periodic forcing as a function of the proportion of inhibitory neurons in the population. The final step (the hard step) will be to introduce inter-neuronal conduction time delays into this model.

Skills/backgrounds required: The more quantitatively trained student should have a strong background in computer programming (Java, C++, Python). The more experimentally trained student should have a strong background in cellular neuroscience and some familiarity with computer programming in one language.

Project 15 (ideally 2 students):
Advisor: John Milton (jmilton@jkecksci.claremont.edu) and Winston Ou (winston.ou@scrippscollege.edu)

Skills/background required: Ideally this project involves two students. One student should have an interest in the study of human movement and be interested in learning how to use high speed motion capture techniques to monitor the movements of various body segments during balancing in response to perturbations. The second student should have a strong mathematical and computer programming background and will be involved in the development of data reduction algorithms.

Project 16 (1-2 students):
Advisor: Lars Schmitz (lschmitz@kecksci.claremont.edu)

The foremost goal of the research in my lab is to achieve a better understanding of the origins of diversity. We describe and analyze macro-evolutionary diversity patterns with an integrative approach, combining phylogenetic inferences from living organisms with paleontological data across large temporal scales. We collect data on multiple levels, including morphological, functional, and ecological diversity of major vertebrate radiations. Data collection and analysis is guided by predictions from functional morphology within the context of major evolutionary transitions in vertebrate history that come with enormous physical challenges and different performance requirements. The main study system of the lab is the vertebrate eye. This project involves comparative analysis of retinal ganglion cell topography in reef fishes. In this project we will investigate whether convergent evolution of zooplanktivory, one of the major feeding niches in reef fishes, is met with similar evolutionary responses in the microstructure of the retina across different species. Zooplanktivory requires high visual acuity for successfully detecting small and partially transparent organisms. We will analyze the topographic distribution of retinal ganglion cells in the retina with stereology methods, and simultaneously develop new techniques for the quantitative analysis and visualization of the data, including new computational techniques to account for the deformation of “flattened” retinas.

Project 17 (1-2 students):
Advisor: Prof. Andrew Steele (steele@kecksci.claremont.edu)

Our lab studies how neural circuits control behavior in laboratory mice. We are particularly interested in how the brain becomes “programmed” to predict scheduled mealtime on circadian (~24 hour) time scales. We use laboratory mice as our model system and have found that the neurotransmitter dopamine is critical for food anticipation. We have also recently determined that the dopamine receptor type 1 (D1R) is essential for mediating the action of dopamine, particularly those receptors located in a part of the brain called the striatum. We are able to determine whether a mouse is anticipating its daily meal(s) by measuring its activity: mice entrained to a feeding schedule always become very active before scheduled meal time, termed “food anticipatory activity” (FAA). D1R knockout mice fail to demonstrate food anticipatory activity. Presently, we are attempting to narrow down the neuro-anatomical region where D1R is required for mediating food anticipation.

This project involves quantitative analysis of immediate-early gene expression in response to scheduled meal time in dopamine receptor 1 knockout mice. We have observed that D1R knockout mice fail to anticipate scheduled meal time on circadian time scales. We would like to examine, in a quantitative manner, the expression of the “immediate-early gene” c-Fos in the brains of wild-type control and D1R knockout mice at different times before and after scheduled meal anticipation. c-Fos has been used extensively in neurobehavioral approaches to determine what part(s) of the brain mediate behavior. By making a careful quantitative comparison of the expression of c-Fos in the brains of mice that show FAA (wild-type controls) and mice that do not (D1R knockouts) we propose to implicate a brain region in mediating FAA. This experiment will involve handling of mice and sectioning of their brains after maintenance on a fixed meal schedule.

Skills/background required: A familiarity with statistics; previous imaging experience or neuro-anatomy will be a major plus.

Project 18 (1-2 students):
Advisor: Prof. Andrew Steele (steele@kecksci.claremont.edu)

This project involves correlating neuronal activity and local field potential in the dorsal striatum of mice anticipating scheduled meals. We have a very large set of electrophysiology data from recordings in the dorsal striatum of mice on various meal schedules. We would like to determine whether the different types of neurons that we recorded from in the dorsal striatum show correlated firing patterns and/or local field potentials with food anticipatory activity. This summer research project will make use of a spike-sorting program developed for our data acquisition system to analyze several TB of data that we have collected, comprising the “dry” component of this project. There is an optional “wet” component of this project, if there is interest. We may implant additional mice with recording electrodes. This will entail three steps: 1) these electrodes need to be assembled; 2) the student will learn the surgical procedure for implantation of electrodes, and 3) set up the data acquisition system.

Skills/background required: Previous programming in Matlab is required. Previous experience analyzing spike data and/or a strong background in statistical analysis desired.

Project 19 (1-2 students):
Advisor: Dr. Adam S. Landsberg (alandsberg@kecksci.claremont.edu)

In its simplest form, a network is just a collection of points connected by lines. However, this simple concept has tremendous utility across many disciplines, from biology to sociology to economics to physics. The points (i.e., “nodes”) in a network can represent people, companies, neurons, etc., while the lines (i.e., “edges”) can represent various types of relationships or interactions between these points. Some well known examples of networks include the neuronal network of the brain, the internet, social networks, and food webs. In this project students will examine various aspects of networks (e.g., types of networks, network measures and metrics, and local/global network structure), and write and/or use computer code to numerically explore various network properties and their applications.

Background/Required Skills: Ideally, students will have had at least one computer programming course (in Python or Matlab), and have completed multivariable calculus.

Project 20 (1-2 students):
Advisor: Dr. Adam S. Landsberg (alandsberg@kecksci.claremont.edu) or Lars Schmitz (lschmitz@kecksci.claremont.edu)

Most camera-type eyes within animals have spherical eye shape, but some groups independently evolved eyes with distinct tubular shape. Best known are owls, but examples are also found among deep-sea fish, deep-sea squid, and nocturnal primates. Members of these groups are mainly active in dim-light environments and hence it has been hypothesized that tubular eye shape is correlated with ecology and lifestyle. However, most other animals that are active in such dark environments maintain camera eyes with spherical shape. The goal of this project is to revisit the function of tubular eye shape by means of optical modeling. In our quantitative analyses we will focus on the question whether tubular eyes meet the requirements of dim-light vision or are a compromise between the requirements of both high light sensitivity and acuity.”

Background/Required Skills: 1 year of intro bio, intro chemistry and intro physics.

HARVEY MUDD COLLEGE

Project 21 (2 students):
The Effect of Stretching on Drug Transport Across Human Skin
Advisor: Nancy Lape (Engineering, lape@hmc.edu)

Human skin provides a two-way barrier that prevents potentially harmful chemicals or diseases from entering the body while slowing water as it exits the body. These barrier effects are mainly due to the brick-and-mortar structure of the outer-most layer of skin, the stratum corneum (SC). The SC is composed of many corneocyte “bricks” linked together by corneodesmosomes in a lipid bilayer continuum “mortar.” In order to reach the bloodstream, any molecule on the surface of the skin must pass through the SC. The ability to understand and modify transport across the SC is therefore crucial for developing new transdermal drug delivery methods and setting dermal exposure limits for toxins. While there is evidence for some transcellular transport across the corneocytes, the majority of the transport across skin is thought to occur intercellularly (i.e. in the lipid bilayer continuum that surrounds the corneocytes). Because the dimensions and nature of the lipid bilayer dictate drug and toxin transport and water loss across skin, a change in the lipid bilayer size and structure would greatly affect this transport. We believe that just such a change must occur upon uniaxial extension of the skin, a viscoelastic tissue: as evidenced by the significantly higher Young’s modulus (a measure of stiffness) of the corneocytes alone (~450 MPa) as compared to intact SC (~ 3-210 MPa), it is likely that extension of the SC results in a major alteration in lipid bilayer dimensions. To examine these effects, we are undertaking in vivo (human subjects) testing of drug transport across stretched and non-stretched (control) sites of skin. We are also using finite element modeling to determine what proportion of changes in transdermal transport is due to geometry only versus geometry and changes to lipid bilayer structure.

Project 22:
Controlling the Cell Phenotype in a Tissue-Engineered Corneal Model
Advisor: Prof. Orwin (Engineering, orwin@hmc.edu)

Corneal keratocytes alter their expressed phenotype in response to wound healing. It has been shown that these phenotypic changes have an effect on the transparency of the tissue. Cells expressing ? smooth muscle actin are present during wound healing when the cornea is hazy, while normal keratocytes in the cornea express high levels of two soluble proteins: transketolase (TKT) and aldehyde dehydrogenase 1 (ALDH 1). RT-PCR, Western blots and immunohistology are being used to assess levels of these three proteins in cells grown in co-culture with endothelial cells in two dimensional and three-dimensional culture environments.

Project 23:
Effect of Bioreactor Culture on Cell Phenotype in a Tissue-Engineered Corneal Model
Advisor: Prof. Orwin (Engineering, orwin@hmc.edu)

Corneal keratocytes alter their expressed phenotype in response to wound healing. It has been shown that these phenotypic changes have an effect on the transparency of the tissue. Cells expressing ? smooth muscle actin are present during wound healing while the cornea is hazy, while normal keratocytes in the cornea express high levels of two soluble proteins: transketolase (TKT) and aldehyde dehydrogenase 1 (ALDH 1). RT-PCR, Western blots and immunohistology will be used to assess levels of these three proteins in cells grown under applied stress in our corneal bioreactor. In addition, finite element modeling and strain characterization of the bioreactor system will be performed in order to optimize the design.

Project 24:
Recreating the Microstructure of the Corneal Stroma
Advisor: Prof. Orwin (Engineering, orwin@hmc.edu)

Our lab has been using type I collagen sponges as the scaffold for our tissue-engineered cornea. We have shown these sponges to be a good substrate for the growth of all three corneal cell types. The structure of these sponges can be visualized in the SEM and OCM and large collagen sheets can be observed. These structures could be contributing to light scatter in the samples. We have recently used electrospinning as a method for creating highly aligned, small diameter type I collagen fibers, which would more accurately reflect in vivo corneal microstructure. This project will involve assessing cell response to aligned collagen fibers as well as incorporating other collagen types and proteoglycans into the aligned mats to more closely mimic the native cornea.

Project 25:
Cell Delivery System for Traumatic Brain Injury
Advisor: Prof. Orwin (Engineering, orwin@hmc.edu)

Our overall project focuses on a cell delivery system to treat traumatic brain injury using novel scaffold materials and human adult stem cell populations. Our approach is novel in that we propose to differentiate human adult stem cell populations in three-dimensional culture in a scaffold specifically designed to recreate the natural microenvironment of neural cells. The cells will be delivered in high density attached to scaffolds optimized for cellular growth and differentiation. One potential summer research project involves culturing adult stem cell populations in two dimensional and three dimensional culture environments with a variety of growth factors to determine optimal differentiation of the cells along neural pathways. Differentiation is assessed via immunofluorescence and Western blotting. We hope to incorporate gene chip analysis into this project in the near future. A second potential research project involves designing new composite collagen/chitosan matrices by gellation or electrospinning and testing them for use in our projects. We are in the process of developing numerous testing strategies, including: cell viability, antibacterial properties, diffusion studies, degradation studies, and mechanical properties.

Project 26 (2 students):
Comparative Genomics in Yeast
Advisor: Prof. Ruye Wang (Engineering, rwang@g.hmc.edu)

This is an interdisciplinary research project in collaboration with a few faculty members in chemistry and biology on different campuses of the Claremont Colleges. Specifically this project is a comparative genomic study of the genetic networks for environmental stress response in the evolutionary context of budding yeast Saccharomyces cerevisiae and fission yeast Schizosaccharomyces pombe. While the project seems biological in nature, it does heavily rely on various computational methods for the quantification and analysis of the biological data, and the modeling of the gene response networks for environmental stress. Different computational algorithms in image processing, data mining, and machine learning are applied in different stages of the project, and new algorithms may need to be developed to address certain specific aspects of the research.

Number of positions: 2 (CS/engineering students interested in biology and biology students interested in computational methods are welcome, programming experience required, C programming experience preferred)

Project 27 (2 students):
Mathematically modeling gene regulation in Drosophila
Advisor: Prof. Dresch (Mathematics, jdresch@g.hmc.edu)

The study of gene regulation has been an important topic in biology for decades. Accompanying the expansion in sequence data, new technologies have provided copious amounts of gene expression data suitable for modeling studies. To better understand the processes of gene regulation, mathematical models have been implemented that describe how DNA sequences direct differentiated gene expression, predict the expression of unknown genes or variants of genes, and reveal the driving forces behind gene regulation. The goal of this project is to use mathematical modeling to investigate the complex molecular machinery involved in regulating gene expression. By implementing modeling approaches involving techniques from a wide range of areas, including data analysis, image processing, sensitivity analysis, model derivation, and parameter estimation, this project will focus on phenomena such as the binding preference of a particular transcription factor, the cooperativity of multiple transcription factors, or the quenching efficiency of particular transcription factors on others.

More details are available at: http://drewell.sites.hmc.edu/projects.html

Project 28 (2 students):
Computational Advances in Biomathematics
Advisor: Prof. Dresch (Mathematics, jdresch@g.hmc.edu)

As more quantitative biological data sets are becoming available, a need for more complex mathematical and statistical analyses has arisen. In earlier bioinformatics studies, many simplifying assumptions were implemented. Now, with computational advances, these assumptions can begin to be removed. For this reason, mathematical models used to study biological systems have been growing in complexity. The goal of this project is to redesign motif search algorithms and improve the computational efficiency in mathematical modeling of biological systems. Using mathematical and computational tools, such as probability, statistics, and algorithm parallelization, this project will focus on utilizing servers available on Harvey Mudd’s campus to improve computations in Biomathematics.

More details are available at: http://drewell.sites.hmc.edu/projects.html

Project 29 (3 students):
Neural Control and Biomechanics of Barefoot Running
Advisor: Prof. Ahn (Biology, aahn@hmc.edu)

Barefoot running requires changes in the neural control and kinematics of running, as we determined last summer. Transitioning to running barefoot after learning to run in cushiony running shoes can take up to a year. This summer, we will runners who have run barefoot or in minimalist shoes for many years to examine their neural control and biomechanics while running barefoot and shod. This project will involve using a high-speed motion-capture system, electromyography, a foot pressure system, and ultrasonography on human subjects.

Project 30 (1 student):
Muscle Power Modulation in Pigeons during Turning Flight
Advisor: Prof. Ahn (Biology, aahn@hmc.edu) in collaboration with Harvard University

The ability to maneuver is crucial to both animals and robots. One component of maneuvering is power production: high maneuverability requires high power. Maneuvering during flight in particular requires very high muscular power, and requires flight power to be adjusted during different stages of maneuvers. Therefore, turning flight in birds lends itself very well for studying how muscular power is modulated from a physiological, and resulting mechanical, point of view. In other words, turning flight can inform us how muscle activation, force production and length changes result in kinematics that generate higher aerodynamic power.

We are looking for a student who is interested in the inner workings of a flying pigeon and who has familiarity with Matlab, in order to to analyze the following data collected on turning pigeons during flight: muscle forces, muscle length changes and neural activation of the main flight muscles, and the accompanying wing kinematics (joint angle changes).

Project 31 (Up to 4 students):
Exploring the regulation of transcription by RpoS in E. coli.
Advisor: Prof. Stoebel (Biology, stoebel@g.hmc.edu)

Bacteria regulate the transcription of their genes to respond to changes in their environment. Global regulatory proteins orchestrate this process, altering levels of transcription of hundreds of genes. Our lab is studying how E. coli uses the protein RpoS to respond to stressful conditions. We have ongoing projects studying how the DNA sequence of particular promoters influences RpoS regulation, as well as how different stresses exert different effects on promoters. These projects involve cloning, creating knock-outs, and measuring transcription with reporter-gene constructs.

In addition, this summer we aim to begin using RNA-seq to study transcriptional regulation at the whole transcriptome level. This approach uses high-throughput sequencing to measure levels of transcription of all genes in the genome. We may explore how stresses influence the transcriptome of different strains, or how variation in the level of RpoS affects the transcriptome within a single strain. These projects will involve RNA isolation, cDNA library construction, and analysis of sequencing data sets. Students with an interest in both experimental work and computational and statistical analysis of very large data sets are encouraged to apply.

Project 32 (Up to 4 students):
Epigenetic regulation of worker sterility in social insects
Advisor: Prof. Drewell (Biology, drewell@g.hmc.edu)

The hallmark of insect societies is sterility of the worker caste. The mechanisms by which sterility evolved are puzzling, as any gene promoting sterility reduces the evolutionary fitness of its bearer. In the honey bee, genes that regulate worker sterility are examples of ‘genes for altruism’ – genes that decrease the fitness of the bearer, but increase the fitness of other individuals in the social group. The goal of this project is to understand the regulation and evolution of these ‘altruistic’ sterility genes. In particular, using a combination of whole genome sequencing, bioinformatics and molecular biology approaches the project will examine evidence for parent-of-origin biased epigenetic modifications, such as DNA methylation, at sterility genes.

Project 33 (Up to 4 students):
Decoding the evolution of cis regulatory modules in Drosophila
Advisor: Prof. Drewell (Biology, drewell@g.hmc.edu)

At the Drosophila melanogaster bithorax complex (BX-C) over 330kb of intergenic DNA is responsible for directing the transcription of just three homeotic 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 there is an underlying code in the spatial clustering of transcription factor binding sites in the CRMs. Utilizing a combination of computational, genetic and molecular approaches the goal will be to analyze the regulatory architecture of BX-C enhancers through molecular dissection and evolutionary comparison across the Drosophila genus.

More details are available at: http://drewell.sites.hmc.edu/projects.html

Project 34 (3 students):
What is the neural basis of decision-making?
Advisor: Prof. Glater (Biology, glater@g.hmc.edu)

In our laboratory, we manipulate neuronal function and examine the effects on decision-making behavior in the free-living nematode, C. elegans. Projects this summer include mapping neuronal circuitry, visualizing neuronal activity in live worms and activating neurons with genetically-encoded Channelrhodopsin (a light-activated ion channel). Techniques used include molecular biology, microscopy, and behavioral assays.

Project 35 (1 student):
Molecular estimation of the soft coral biodiversity of Dongsha Atoll, Taiwan
Advisor: Prof. McFadden (Biology, mcfadden@g.hmc.edu)

The island of Taiwan straddles the Tropic of Cancer (~23°N latitude), which is the northern geographic limit of most coral reefs. Although the Penghu Archipelago, an island group located west of Taiwan at 23.3°N, has no true coral reef development, a recent biodiversity survey nonetheless found 33 species of alcyoniid soft corals belonging to groups normally associated with reefs. A similar survey of Dongsha Atoll, a true coral reef located southwest of Taiwan at 20°N, has now been conducted, and the goal of this project will be to estimate the biodiversity of soft corals from Dongsha for comparison with the more northern Penghu Archipelago. Soft corals are problematic to identify to species using morphological characters, as the traits that distinguish species reliably are not well understood. We will instead use species-specific DNA sequences (“DNA barcodes”) to distinguish species, and use genetic measures to compare the numbers and identities of soft coral species between Dongsha and Penghu. The project will require extraction of DNA from preserved specimens, amplification of mtMutS, COI and 28S rDNA genes using PCR, preparation of amplified DNA for sequencing, and subsequent sequence analysis.

Pre-requisite: Bio52.

Project 36 (1 student):
Phylogenetic relationships of the xeniid soft corals of Taiwan
Advisor: Prof. McFadden (Biology, mcfadden@g.hmc.edu)

Xeniidae is a family of small soft corals that are common on coral reefs and in the aquarium trade. Interest in the ecology of xeniids is growing because they appear to colonize reefs rapidly following environmental disturbance events, and in some situations can prevent the recovery of reef-building corals. Our understanding of species boundaries and evolutionary relationships among xeniids is very poor, however, and many species cannot be identified reliably. Working with a collection of xeniids from Indonesia, we have recently shown that a molecular “barcode” consisting of DNA sequences from three different genes can be used to distinguish species that cannot otherwise be identified with certainty. The goal of this project is to use that molecular barcode to identify species of xeniids that have been collected in a recent survey from Taiwan, near the northernmost geographic limit of xeniids, and to compare the identities and diversity of species between Taiwan and Indonesia, the geographic center of coral biodiversity. The project will require extraction of DNA from preserved specimens, amplification of mtMutS, COI and 28S rDNA genes using PCR, preparation of amplified DNA for sequencing, and subsequent sequence analysis.

Pre-requisite: Bio52.

Project 37 (2 students):
Molecular and bioinformatic analyses of the mitochondrial mutS DNA repair mechanism in octocorals
Advisor: Prof. McFadden (Biology, mcfadden@g.hmc.edu)

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, believed to have been acquired by horizontal gene transfer from a giant virus, evolves rapidly by a process that includes many insertions and deletions of amino acids; as a result, the mtMutS proteins of different octocoral genera and families differ greatly in sequence and presumably also in function and efficiency. Two projects are available for summer 2013 to explore the relationship between mtMutS and evolutionary rate in octocorals. These include: (1) Obtaining complete sequences of mtMutS for octocorals in families with different apparent rates of mt gene evolution to (a) identify conservative vs. variable regions of the gene and (b) infer bioinformatically those regions of the gene most important for its repair function. (2) Obtain partial or complete mitochondrial genome sequences for one or more of the species we suspect lack a functional mtMutS protein to determine the influence of mtMutS on mitochondrial gene order.

Pre-requisites: Bio111 or previous molecular biology lab experience.

Project 38 (1 student):
A RAD-sequencing approach to species boundary detection in soft corals
Advisor: Prof. McFadden (Biology, mcfadden@g.hmc.edu)

The study of population genetic processes, speciation and hybridization in corals has been greatly hindered by their slow rates of mitochondrial gene evolution relative to other animals, and by the labor and expense involved in developing species-specific genetic markers such as microsatellites. Restriction-site Associated DNA (RAD) sequencing is a promising new method that uses next generation sequencing technology to identify single-nucleotide polymorphisms (SNPs) and other genomic markers that can be used to study population-level genetic variation. The goal of this project is to test the power of RAD-sequencing to detect species boundaries among closely related species of soft corals in the genus Alcyonium. This genus includes 10 closely related Mediterranean and N. Atlantic species, several of which are suspected to have originated by a process of hybrid speciation. A wealth of information from traditional molecular markers already exists for this group, making it an ideal case to use to test the ability of RAD-sequencing to discriminate species boundaries and hybrid origins in octocorals. (Note: Funding for this project is pending and may not materialize.)

Pre-requisites: Bio111 or previous molecular biology lab experience.

POMONA COLLEGE

Project 39 (2 students):
Kinematics of accelerating, decelerating and turning in running mites
Advisors: Anna Ahn (Biology, HMC), Dwight Whitaker (Physics, Pomona) and Jonathan Wright (Biology, Pomona)

The locally endemic mite Paratarsotomus macropalpis is an extreme thermophile and is active on the ground surface in temperatures between 20 and 60 ºC. At higher temperatures, the leg muscles function at remarkable contraction frequencies. In a recent paper (Wu et al., 2010; J. exp. Biol. 213, 2551-2556) we documented stride frequencies ranging from 93 Hz at 25ºC to 111 Hz at 45ºC, the highest reported for any weight-bearing muscle. Accompanying measurements of relative speed in the lab (129-133 body lengths s-1) are also exceptional and subsequent measurements of animals running in situ at 57 ºC show even greater speeds (200-220 bl s-1). When running in situ, the mites move erratically, often stopping abruptly and making abrupt changes in direction.

The proposed research will expand studies of the mite locomotion to address three key questions:

1. Are the even higher running speeds measured in situ attained by increases in stride frequency or by increased stride length above a maximum stride frequency?

2. How rapidly can mites stop and can the deceleration be explained by drag forces in air or would it depend on braking forces?

3. How do mites achieve the abrupt changes in direction?

These will be explored by filming mites in the field (in situ) and in the lab using a high speed video and frequency video camera and then using frame-by-frame analysis to perform kinematic analysis of stride patterns, stride lengths, gait changes, and other kinematic variables. These studies promise to expand our understanding of several physiological processes including how the performance of ultrafast muscles relates to temperature, whether mites alter their drag profile and Reynolds number to facilitate deceleration, and whether elastic energy storage in cuticle ligaments plays a significant role in braking and turning.

Project 40:
Raman spectroscopy of Multicomponent Lipid Bilayers
Advisor: Alfred Kwok

The lipid rafts hypothesis puts forth the idea that cholesterol-rich nanoscale spatial domains exists in cell membranes. It has been hypothesized that these domains are enriched in sphingomyelin and cholesterol, and can serve as platforms for signaling proteins to aggregate. Before a model can be developed to understand protein-lipid interaction in these rafts, we need to understand the interaction between different lipid molecules. Lipid bilayers supported on quartz substrates maintain the fluid properties of lipid bilayers in cell membranes and serve as good laboratory models to study the interaction between sphingomyelin and cholesterol in lipid bilayers consisting of multi-component lipid mixtures.

Raman spectroscopy, complimentary to infrared spectroscopy, is a common technique for studying the vibrational modes of, and thus the interaction between, molecules. Moreover, the Raman spectra of individual molecules can serve as their vibrational fingerprints. We will study the feasibility of using Raman spectroscopy to determine the concentration of cholesterol in supported bilayers consisting of binary mixtures of POPC ( 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, an asymmetric phosphatidycholine) and cholesterol. We will first develop a set of spectral standards by obtaining the Raman spectra of POPC:cholesterol lipid bilayers with different cholesterol concentration before applying these standards to determine the cholesterol concentration in a lipid bilayer with unknown cholesterol concentration. Since the Raman spectrum of an individual POPC or cholesterol is complex, partial least squares analysis and related statistical techniques such as principle component analysis will have to be used to analyze the spectra of various binary mixtures and establish the spectral standards.

Project 41:
Exploring evolutionary and population dynamics in ciliates via computer simulation
Advisor: Professor Andre Cavalcanti (Biology)

Ciliates are a group of unicellular eukaryotes characterized by the presence of cilia and nuclear dimorphism. Each ciliate cell has two types of nuclei, a genetic micronucleus and a somatic macronucleus. The micronucleus (MIC) is transcriptionally silent and used to exchange genetic material during sexual conjugation. The macronucleus (MAC) is used to generate the transcripts necessary for cell function. The DNA organization is widely different in these two nuclei. While the MIC is diploid and divides by mitosis, the MAC is highly polyploid. During asexual division, the MAC divides through a process called amitosis. Amitosis distributes the DNA to the two daughter cells at random, with no guarantee that either daughter will have the correct number of chromosomes or even the necessary genes. These errors can accumulate over successive divisions until the ciliate undergoes sexual reproduction. At this point, conjugating cells exchange haploid micronuclei and the old MAC is destroyed and replaced by a new one generated from the zygotic MIC. This unusual process creates interesting behaviors and dynamics, and, even among ciliates, the specific organization of the MAC can vary wildly. For example, in Spirotrichs the MAC contains upward of a thousand copies of each gene but only possesses 2% of the genetic material in the MIC.

In an attempt to explain the evolutionary pressures behind this organization, my group, in collaboration with Prof Ami Radunskaya (Math, Pomona College) has performed simulations which model the ciliate cell cycle and a manuscript is currently under review. In another project we showed that at least for an idealized infinite population the presence of amitosis could lead to an increased mutational load in ciliate cells. We plan to continue to address these problems next summer. For example, there has been a proposal that Tetrahymena, a model ciliate, experiences strong selection against chromosomal imbalances and errors in the MAC, thus preventing the accumulation of imbalances and errors over multiple generations of asexual growth. Using the known characteristics of Tetrahymena, we can simulate its lifecycle and test whether this mechanism is sufficient to maintain a working MAC or if further regulation is necessary. In addition, we want to extend the study of mutational load in ciliates by simulating finite populations.

Project 42:
Exploring Raman Spectroscopy’s Applications in Medical Diagnoses
Advisor: Professor Charles Taylor (Chemistry)

This collaborative project involving researchers at Pomona College and Keck Graduate Institute is entering its second phase. Its overarching goal is to establish Raman spectroscopy’s utility as a diagnostic method for identifying bacterial infections and metabolic disorders based on volatile organic compounds (VOCs) found in growing cell cultures. Previous research has shown that some VOCs in exhaled breath such as low molecular weight hydrocarbons, aldehydes, ketones and amines, may be used as diagnostics or indicators for various diseases such as tuberculosis, lung cancer, hepatic dysfunction or metabolic disorders.

While other work examining biomarkers has focused on more conventional methods, such as gas chromatography or sensor arrays, this work employs a novel sampling geometry which uses evanescent field excitation to enhance Raman spectroscopy’s sensitivity towards VOCs. This project aims to build a Raman-based platform for medical diagnoses that uses commercially available sorbents to collect and concentrate VOCs above bacterial cultures then desorb them onto a polymer-coated lens within the spectrometer and measure the resulting mixture’s spectrum. We have measured the VOCs in the headspace of several different bacteria using GC-MS and have identified several compounds whose presence and/or relative abundance may be used to help identify the type of bacteria. We have refined our system to improve our analytical results and will be repeating our preliminary experiments this summer. The common pathogens, E.coli, Pseudomonas aeruginosa and Staphlococcus aureus will lead the way. Cultures will be grown in the Biosafety Level 2 laboratory at KGI and the analyses performed at Pomona College.

Quantitative/analytical methods employed in these studies will include: principle component analysis (PCA), for type classification, GC-MS for determining VOC relative abundances and quantitative structure activity relationships (QSAR) for selecting polymers used to coat the Raman sensor optic. In addition, molecular modeling software will be used in conjunction with the GC-MS data to predict/identify spectral regions of interest.

Project 43:
The role of GDI in rab GTPase placement in endocytosis
Advisor: Prof. Clarissa Cheney (Biology)

In this lab, we use Drosophila mutants, Drosophila transgenic lines and bacterially expressed recombinant Drosophila proteins to explore how GDP dissociation inhibitor (GDI) controls the placement of rab GTPases on membrane-bound intracellular vesicles. Rabs determine which target membrane a vesicle fuses with and so rabs determine the directionality of vesicle transport. Though higher organisms have many rabs, each specific for a particular step of the transport pathway, there are far fewer GDI genes. For example, flies have 30 rabs, but only 1 form of GDI. Thus, the puzzle is: how does this single GDI “know” to place the right rab on the right membrane?

Within this broad context, there are several projects with a quantitative emphasis:

1. Disturbances of vesicle transport in a GDI mutant. Prior work in this lab indicates that the L319 GDI mutant has enlarged endocytotic vesicles. We would like to determine whether these vesicles are stuck in early endocytosis or whether they send their cargo on at the normal rate. One possible avenue of analysis could be FRAP (fluorescent recovery after photobleaching), using a fluorescent endocytic cargo.

2. Why is there an overabundance of blood cells in L319 GDI mutant Drosophila larvae? One hypothesis to explain this is that blood cells overproliferate in the larval lymph gland. We would like to measure the number of dividing cells in the lymph glands of this mutant and also measure their rate of cell division. We suspect that impaired endocytosis in this mutant results in too much JAK-STAT signaling. A failure of endocytic degradation could result in a constant “on” signal for cell division. We would like to test this hypothesis, using fluorescent and non-fluorescent JAK-STAT reporters, quantitative Westerns and quantitative fluorescence microscopy.

3. What is the role of N-terminal acetylation in GDI function? Prior work in the lab indicates that GDI is N-terminally acetylated by Psidin. We would like to know if this N-terminal acetylation affects the affinity of GDI for rabs and also would like to know how tightly Psidin binds to GDI.

Projects 1 and 2 involve using fluorescent report, quantitative analysis of microscopic images and quantitative Westerns. Project 3 involves expressing Drosophila proteins in bacteria, isolating them and then measuring the affinity of their binding.

Project 44:
Development of new optimized antimalarial drugs
Advisor: Professor Cynthia Selassie (Chemistry)

Malaria continues to be a devastating infectious disease that is a major cause of morbidity and mortality around the globe. In the absence of an effective vaccine, chemotherapy continues to be the only method of combating this disease. Unfortunately, the increase in parasitic resistance to currently used drugs reduces their efficacy in malaria-endemic regions. There is thus an urgent need for the development of novel antimalarials.

Our approach is to exploit and develop a number of 4.6-diamino-1,2-dihydro-2,2-dimethyl-1-(3’-(3”-X-anilinomethyl)phenyl)-s-triazines since a few model compounds show potent antiplasmodial activity against strains of D6 and Dd2 Plasmodium falciparum(Pf) that are sensitive and resistant to Chloroquine(CQ), respectively. They are also potent inhibitors of the bifunctional thymidylate synthase-dihydrofolate reductase from (Pf).

The goal of this research is to optimize the activity and selectivity of these existing lead molecules by using a quantitative structure-activity relationship (QSAR) approach. Compounds will thus be designed using CQSAR software, synthesized and evaluated versus the Pf enzyme and the CQ sensitive, and resistant plasmodial cultures. Cytotoxicity assessments will also be carried out versus HL-60 cells.

Project 45:
A study of the efficiency of spore launch by Sphagnum moss vortex rings
Advisor: Professor Dwight Whitaker (Physics)

Our group has observed that when the capsules of Sphagnum moss explode, a vortex ring is created that carries spores to heights where they can be dispersed by turbulent air currents over long distances. This method of dispersal has been very successful for Sphagnum whose genus covers more than 1% of the Earth’s land area despite being a nonvascular bryophyte that can only live in wet habitats. Using computational fluid dynamics (CFD) software to model the flow from capsules, we have learned that the vortex rings produced by Sphagnum are not “optimal.” An optimal vortex ring maximizes the impulse to the moving fluid, which, in turn, maximizes thrust when a vortex ring is used for locomotion. This is said to explain why all the vortex rings produced by animals (e.g. squid, jellyfish, and in a healthy human heart) are measured to be optimal.

Our research this summer hopes to answer the question of whether the ‘suboptimal’ vortex rings from Sphagnum are actually more efficient at carrying spores than a more powerful optimal vortex ring. To do this, students will run and modify software the uses fluid flow data from our CFD simulations to quantify the dispersion of particles in the flow field. Field observations have indicated that there is a variation in vortex ring velocity with spore size across different species. Our calculations will determine if this shift in vortex ring impulse optimizes the vortex rings for spore size.

Project 46:
Reaction efficiency of diffusion-controlled processes on finite Euclidean and Fractal Lattices.
Advisor: Prof. Roberto A. Garza-López (Chemistry)

We explore the consequences of metrically decomposing a finite phase space, modeled as a d-dimensional lattice, into disjoint subspaces (lattices). Ergodic flows of a test particle undergoing an unbiased random walk are characterized by implementing the theory of finite Markov processes. Insights drawn from number theory are used to design the sublattices, the roles of lattice symmetry and system dimensionality are separately considered, and new lattice invariance relations are derived to corroborate the numerical accuracy of the calculated results. We also look at the efficiency of catalytic surfaces as a function of dimensionality, size and imperfections on the surfaces. This work is important in physics, chemistry, biology, neurosciences and geology. Students will be introduced to programming in Maple, Matlab and Mathematica to generate results which will be analyzed statistically to study diffusion-controlled reactions on these architectures. For this specific project, we work with other groups in the States and in India.

Project 47:
Interaction of ferritin and Scara-5 and and their role in iron regulation
Advisors: Professors Mal Johal and Mat Sazinsky

Project Overview: Diabetics are more susceptible to bacterial infection than the general population. It is not understood why this is, but recent evidence suggests that diabetics have trouble properly regulating iron and that this dysregulation plays a significant role in compromising their immune system. Iron is a growth-limiting micronutrient for most living organisms including bacteria. Consequently, complex regulatory mechanisms in the body sequester free iron as an immune defense against bacterial infection. Unfortunately for diabetics, common traits including insulin resistance, blood sugar levels and obesity hypertension all exhibit a positive correlation with the amount of serum ferritin, an iron storage protein closely related to total body iron, and rates of infection. How these traits are linked is currently unknown. Students will split their time equally between the Johal and Sazinsky laboratories over the duration of the summer. This funding will be used to support one summer student who will perform initial purification, structural analysis and binding kinetics of ferritin with its receptor, Scara5. The student will also use/develop/refine mathematical models to obtain binding constants.

Project Description: While the intracellular structural and functional role of ferritin is well characterized, the role of serum ferritin is not fully understood, and the consequence of serum ferritin glycation even less so. Recently it was found that Scara5 mediates L-ferritin endocytosis in embryonic kidneys, demonstrating that ferritin can serve as the secondary form of iron transport. Detailed information about the interaction between Scara5 and L-ferritin as well as the structure of Scara5 has yet to be determined, presenting a great obstacle for further understanding of ferritin-Scara5 interactions and the role of glycation on iron regulation and consequently infection. This project aims to to characterize the kinetics of receptor interaction with glycated and non-glycated ferritin using a QCM-D and other biophysical techniques. These experiments will provide insight into the causes of higher serum iron levels observed in diabetics. Additional opportunities exist to determine the X-ray crystal structure of Scara5, which will aid in our precise understanding of how glycation effects the complex formed between Scara5 and ferritin.

Skills/background required: Students should have a strong general background in biology and chemistry and a demonstrated interest in either biochemistry or biophysics.

Project 48:
Sparse canonical correlation (SCCA) as a tool in multivariate analysis.
Advisor: Professor Johanna Hardin (Mathematics)

As high-throughput data become ubiquitous, there has become a need for making multivariate statistical techniques useful for such large genomic datasets. Of particular interest to our work is correlating different multivariate sets of data (e.g., phenotypic data, microarray data, RNA-seq data, etc.) Previous studies have explored the use of Canonical Correlation Analysis (CCA) as a technique for investigating the relationships between sets of multivariate data. CCA maximizes the correlation between linear combinations of each of the two data sets, and produces a list of independent pairs of linear combinations organized by correlation. Our work extends CCA in two directions.

First, standard CCA is extremely sensitive to outlying values, and as most high throughput data are characteristically noisy, we investigate the effects of adding a robust estimator to CCA. We have already had success under certain models of recovering the known structure when substantial noise was added to the data. Secondly, with large datasets, interpretability is gained by setting certain coefficients to zero (this is known as sparse canonical correlation, SCCA). SCCA has had success in the genomics literature, but there have been no attempts to make the methods resistant to outlying values. The HHMI SURP will investigate resistant SCCA in the context of both simulated and publically available data.

Project 49:
The Origins of Adaptive Immunity (Experimental) and Some Computational Projects
Advisor: Jonathan Moore (Pomona)

My research examines the evolutionary origins of adaptive immunity, the branch of the immune system utilizing B and T cells and conferring resistance to many common infectious diseases. To this end, I research the transcriptional control of immune genes in sea lamprey and bony fishes. Of particular interest is the control of the lamprey's VLR-B gene, a gene functionally analogous to antibody genes but with no evolutionary homology to them. Through experiments with the lamprey and their DNA, and also catfish cell culture cells, we are determining whether or not the transcriptional control elements are shared between these two different immune systems, which provides increasing evidence as to their evolution.

Also, I do have computational and mathematical biology projects: (1) the assembly and analysis of the VLR-B locus, (2) the continuation of a mathematical biology project on graph theory trees, and (3) the programing of some bioinformatic methods we have developed.

Project 50:
Examining the relationship between structure and unnatural function in mutants of Taq DNA polymerase.
Advisors: Professors Aaron Leconte (KSD) and Matt Sazinsky (Pomona).

Project Overview: We are interested in studying how proteins evolve new function in the laboratory from both a biochemical and structural perspective.

Students will split their time approximately equally between the Leconte and Sazinsky labs over the duration of the summer. This funding will be used to support one summer student who will perform initial purification, crystallization, structural analysis and activity characterization of recombinant Taq DNA polymerase.

Project Description: DNA is a valuable biotechnological tool, but its utility is limited by the narrow substrate scope of DNA polymerases. Thus, researchers have spent significant time and effort attempting to alter the properties of DNA polymerases using laboratory evolution. The most common target of these efforts is DNA polymerase I from T. aquaticus (Taq); to date, over 20 DNA polymerase mutants of Taq (possessing over 60 distinct mutations) have been published. In spite of these numerous efforts to evolve new activities, there have not been, to date, any systematic or quantitative structure-function studies to begin to understand the biochemical and biophysical role of the mutations observed in these prior studies. Such studies might lead to a better understanding of unnatural substrate recognition by Taq, leading to more useful DNA polymerases as well as a better understanding of how proteins evolve new function, in general.

We are collaborating on a project to quantitatively characterize the relationship between structure and unnatural function in mutants of Taq DNA polymerase. In the Leconte laboratory (Keck Science Department), mutant DNA polymerases will be generated and evaluated for their ability to recognize a panel of related unnatural substrates. The activity of mutant polymerases will be carefully quantified using steady-state kinetics, which enable for the precise calculation of the rate of modified DNA synthesis. X-ray crystal structures of the different mutant proteins will be determined and computationally refined in the Sazinsky laboratory (Pomona College). Together, these experiments allow for meticulous examination and comparison of the relationships between mutations and unnatural functions. We anticipate that this will be the first step in a fruitful collaboration that explores the evolution of new function both biochemically and structurally.

Skills/background required: Students should have a strong general background in biology and chemistry and a demonstrated interest in either biochemistry or biophysics.

Project 51:
Using comparative genomics to understand evolution of the environmental stress response in yeast Saccharomyces spp.
Advisor: Professor Tina Negritto (Biology)

One of the projects in my lab consists of a comparative genomic study of the genetic networks for environmental stress response in the evolutionary context of budding yeast Saccharomyces cerevisiae and fission yeast Schizosaccharomyces pombe. This project is possible due to an ongoing collaboration with several colleagues from the different Claremont Colleges that are chemists, biologists and engineers. The stress factors chosen to use in our studies consist of phenol derivatives that are naturally occurring or synthetic compounds that not only humans are exposed to, but are also found in the environment affecting plant life and that of other eukaryotes. We would like to identify the genetic network that allows organisms to survive and respond to environmental stress factors. The model systems we choose to use are budding and fission yeast since deletion libraries are available, a collection of strains in which each strain has a different gene deleted (a deletion library consists of about 4700 strains). Screening these libraries will allow us to identify genes that play a role in the cellular response to a particular or general stress. Genetic networks for budding and fission yeast will be identified and compared, such that the following questions can be addressed: are components of the response networks conserved through evolution? Are DNA checkpoint/repair, cell cycle control, and ER-stress signaling critical for cellular survival to environmental stress? Genomic analysis, data mining, data digitalization and quantification are used to construct profiles of gene response networks for environmental stress.

Project 52:
Spatial Variability in Arthropod Community Structure in Coastal Sage Scrub (CSS)
Advisors: Professors Wallace Meyer and Jonathan Wright (Biology)

Background: Eighty-five percent of all animal species are arthropods (insects, spiders, etc.). Because of this staggering diversity, fundamental questions such as how many and what species reside in a region and how they got there typically remain unanswered. Consequently, managers are ill-equipped to make informed decisions concerning the preservation of arthropods or to predict how arthropods will respond to perturbations (e.g., climate change, fragmentation). This is especially pertinent for arthropod species in Southern California that require coastal sage scrub (CSS) ecosystems for their survival. The CSS ecosystem is listed as endangered (85-98% lost) by the USGS, and as critically endangered by the World Wildlife Fund. Estimates suggest that stands of CSS are reduced to less than 10% of their original distribution, and much of the remaining CSS is damaged, requiring restoration efforts, and found in small isolated patches that are typically long and narrow, increasing the deleterious impact of edge effects. As such, determining which species are only found in the CSS and examining differences among patches of CSS in Southern California will allow us to better understand the status and biogeography of CSS species in order to identify species that are at risk of extinction and require conservation attention.

SURP Project: We are looking for an undergraduate who is interested in the conservation of arthropod biodiversity. This undergraduate will work with both Meyer and Wright in the summer of 2013 to: (1) examine differences in arthropod communities found among habitat types (CSS, recovering CSS, and non-native grasslands) at the BFS and (2) compare differences among arthropod communities found in the BFS to those found in the surrounding suburban/urban areas immediately adjacent to the BFS to identify if there is a soil arthropod assemblage unique to BFS. This study will be the first detailed investigation of soil arthropod diversity and distribution in and outside a CSS habitat patch and results will provide needed baseline data to effectively manage CSS arthropods and ecosystems both at the BFS and elsewhere. We would prefer to work with someone who is interested in continuing the project after the SURP is completed.

Learning Objectives: Meyer and Wright will teach the student to collect, preserve and identify different arthropod taxa. In addition, the student will work with Meyer to learn to effectively use the statistical program PRIMER-E v.6. This program has wide range of univariate, graphical and multivariate routines for analyzing arrays of species-by-samples data which is critical for any community ecologist. Meyer and the student will read the PRIMER manual, discuss approaches to examine and describe differences in these arthropod communities, and execute these analyses.

Project 53 (1-2 students):
3-D Mathematical modeling of tumor growth
Advisors: Professors Ami Radunskaya (Pomona) and Lisette dePillis (Math, HMC)

We will extend past work on models of tumor growth and metastasis. In this project, we will develop a three-dimensional hybrid cellular automaton model of pediatric gliomas. We will validate the model with data from our collaborators’ clinical practice. Our goal is to use the model to gain a better understanding of tumorogenisis in this particular situation, focusing on the role of the micro-environment. Previous laboratory studies suggests several mechanisms that can be explored using the implemented model.

Skills/backgrounds required: Facility computing in Matlab, some familiarity with parallel methods a plus. Some background in partial differential equations. Enough biology to understand research papers in clinical oncology.