Keep in mind that students from any college can apply for any of the listed positions.
Please contact individual advisors with questions about projects and to make appointments to meet. Contact Prof. Stoebel (email@example.com) if you have additional questions.
KECK SCIENCE DEPARTMENT (KSD)
Ecology and Evolution (KSD)Project 1
Dynamic Energy Budget of Barnacles and Snails
Advisor: Professor Sarah Gilman (firstname.lastname@example.org)
The goal of this project is to use dynamic energy budget theory to develop mathematical models of the growth and survival of intertidal animals. Intertidal shores, which alternate between terrestrial and marine conditions, provide a thermally challenging environment, and organisms may experience shifts in body temperature of up to 30 °C over a single day. Dynamic Energy Budget models calculate an organism’s growth and reproduction rates from basic information about how energy use changes with body size and temperature. I am in the process of developing such a model for the intertidal barnacle Balanus glandula and snail Nucella ostrina based on laboratory data we are currently collecting. A student involved in this project would help develop and test the model.
Skills/background required: Ideally this project will involve two students working collaboratively on both the data collection and model building. One student should have a familiarity with basic concepts in ecology and physiology will be helpful. The other should have some prior experience with Matlab. This project will include laboratory, field, and computer modeling components.Project 2
Predicting Body Temperatures of Intertidal Organisms
Advisor: Professor Sarah Gilman (email@example.com)
The first step in predicting how an organism will respond to climate change is understanding how climate change will alter the organism’s body temperature. Most 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: A familiarity with basic concepts in physiology and physics will be helpful. Some prior programming experience is required. This project could include field work.Project 3
The Origins of Diversity
Advisor: Professor Lars Schmitz (firstname.lastname@example.org)
The foremost goal of the research in my lab is to achieve a better understanding of the origins of diversity. In the summer of 2014 we will focus on the tempo and mode of morphological evolution in birds. This project is part of an ongoing, collaborative effort to analyze macroevolutionary diversity patterns with an integrative approach, combining phylogenetic inferences from living organisms with paleontological data across large temporal scales. Our data collection is guided by predictions from functional morphology within the context of major evolutionary transitions in vertebrate history that come with different performance requirements. The project involves extensive data collection on museum specimens, thorough examination of published ecological information, and the application of advanced multivariate statistics and state-of-the-art phylogenetic comparative methods.
Skills/background required: This project ideally involves students with strong statistical preparation, ability to manipulate large datasets, R-knowledge, and keen interest in evolutionary biology.Project 4
Quantifying Marine Environmental Change
Advisor: Professor Branwen Williams (email@example.com)
Records of environmental change derived from marine organisms including corals can tell us how anthropogenic change has altered our oceans. These records are created by measuring the physical, chemical, and/or biological properties of coral skeletons. These properties in corals will change in response to environmental variability. For example, specific trace elements in the skeleton of corals will fluctuate in response to seasonal variability in ambient seawater temperature. In addition, these corals form growth bands in the skeleton like trees form tree rings that can provide a timeline of the coral growth. This allows us to assign specific years to the records that we create, records that in long-lived corals will extend several hundred years into the past. The project proposed here will use statistical analyses of such records to explore variability in carbon and nitrogen cycling or temperature patterns in the oceans. Students may be involved in generating the data, statistical analysis of the resulting environmental records, and comparisons with existing instrumental datasets to assist with interpretation.
Skills/background required: Prior programming experience, preferably Matlab, and some background in statistics.
Molecular Biology (KSD)Project 5
Analysis of Gene Expression in Drosophila
Advisor: Professor Jennifer Armstrong (firstname.lastname@example.org)
The Armstrong laboratory is interested in the problem of gene expression in the context of chromatin. The basic unit of chromatin is the nucleosome, which consists of 147 bp of DNA wrapped around eight core histones. In vitro, nucleosomes inhibit several stages in the process of DNA transcription; our cells have devised a complex system of protein machines that orchestrate changes to chromatin to regulate gene expression. The Armstrong laboratory is currently focused on one of these protein machines, CHD1, a protein conserved from yeast to humans. This project will use the model organism Drosophila melanogaster (the fruit fly) together with the quantitative technique of reverse-transcriptase, real-time PCR to study gene expression in various tissues in flies lacking the CHD1 machine as compared to wild type flies. Time permitting, this project will go on to examine gene expression in flies lacking putative CHD1 interacting partners.
Skills/background required: Experience with Excel and basic molecular biology techniques is required.Project 6
Investigating the Molecular and Genetic Basis of Embryonic Lethality Caused by Circular Sex Chromosomes
Advisor: Professor Patrick Ferree (email@example.com)
Abnormally circularized chromosomes are associated with a number of human genetic conditions such as Turner’s syndrome, and they can cause severe mitotic defects during development. In some cases, these circular chromosomes can even be lethal, but the basis is not understood. Using D. melanogaster (the fruit fly) as a genetic model organism, we performed a genetic screen in order to identify different chromosome regions in the genome that influence the level of embryonic lethality caused by a circular X chromosome. We discovered a single small region on chromosome number 3 that dramatically elevates lethality; in this region there are four genes that we consider as strong candidates for causing the lethality. Interestingly, three of these genes encode non-protein-coding RNAs. This is a very exciting finding because previous studies have found that non-coding RNAs are involved in a number of important processes such as X chromosome inactivation and also in certain human cancers.
In this summer project, a student will learn to perform a method known as quantitative PCR in order to carefully measure RNA levels expressed from these four candidate genes. Their expression levels will be compared between two different fly strains, one showing very high embryonic lethality and another one showing very low embryonic lethality. The prediction is that there will be at least a 2 to 5-fold difference between these lines for a gene that underlies the lethal effect. This project can potentially lead to the use of transgenics to further test how candidate gene(s) operate to cause lethality.
Skills/background required: Some experience with basic PCR would be helpful for this project. Basic requirements are a zeal for learning and conducting meticulous molecular experiments, and a willingness to troubleshoot experimental conditions with enthusiasm.
Project 7 has been withdrawn.
Project 8 (1-2 students)
Biochemical and Structural Perspectives of Protein Evolution.
Advisors: Professors Aaron Leconte (KSD, firstname.lastname@example.org) and Matt Sazinsky (Pomona, email@example.com).
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. (Students will split their time approximately equally between the Leconte and Sazinsky labs over the duration of the summer.) 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 amino acid mutations and the acquisition of unnatural function. Last summer, a student successfully developed a purification protocol for Taq DNA polymerase. The student this summer will largely focus on crystallization and initial structural characterization. This is part of an ongoing 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 9 (1-2 students):
Genetic Networks in Yeast
Advisor: Professor Zhaohua Irene Tang (firstname.lastname@example.org)
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 9b (1 student)
Genetic Networks in Yeast
Advisor: Professor Gretchen Edwalds-Gilbert (email@example.com)
This project uses the model eukaryote Saccharomyces cerevisiae to address the questions described in project 9 in collaboration with Professor Tang’s lab. We have identified probable response networks, which students will investigate further using a variety of molecular/cellular biology andquantitative analyses.
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):
F-Box Proteins in Arabidopsis
Advisor: Professor Bryan Thines (firstname.lastname@example.org)
Eukaryotic cells selectively remove certain proteins to alter their proteome in response to the environment or other signals. F-box proteins confer specificity to this protein removal by marking target proteins for degradation. Astoundingly, the model plant 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 using hierarchical clustering across multiple stresses and time points, as well as other data mining strategies, 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/background required: Some background in statistics and molecular biology is required and some previous experience with R is helpful, but not required.
Project 11 (1-2 students):
Lipid/Protein Interactions in Membrane Gradients
Advisor: Professor Babak Sanii (email@example.com)
We investigate the properties of materials that are inspired by biology. For example, we study self-healing systems by incorporating the same lipids found in cell membranes, and we create reactive materials by mimicking the folding pathways of proteins. Projects are collaborative and as open as possible, with a strong emphasis on sharing the tools we develop. We are also builders and inventors, using tools such as 3D printing and economic optical design to improve our capabilities and to develop more cost-effective scientific equipment for others.
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, with the diffusion coefficient determined by Fourier analysis of fluorescence-microscopy movies. We will apply this system to determine preferred protein-adhesion environments (e.g., inactivated-cholera and GM1 lipids), as well as investigate cholesterol-transport between dissimilar lipid membrane compositions.
Skills/background required: Calculus, basic optical microscopy, safe lab habits, willingness to collaborate on projects.
Concentration-dependent cholesterol transport in lipid membranes
Rachel Levy (HMC Mathematics, firstname.lastname@example.org) and Babak Sanii (KSD Chemistry, email@example.com)
The diffusion of cholesterol in lipid membranes is complicated because the very presence of cholesterol dramatically alters the membrane’s diffusion coefficient. In this project we will produce a simplified physical chemistry system to experimentally measure cholesterol transport, and apply computational mathematical methods to model the phenomenon. If successful, we aim to quantitatively understand the complex relation- ship between cholesterol concentration and local membrane diffusion for a given phospholipid. Additionally we will then have a platform to rapidly determine this relationship for any given phospholipid composition.
Neuroscience/Physics (KSD)Project 12
Computational Exploration of Networks
Advisor: Professor Adam Landsberg (firstname.lastname@example.org)
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.
Skills/background required: Ideally, students will have had at least one computer programming course (in Python or Matlab) and will have completed multivariable calculus.
HARVEY MUDD COLLEGE
Pulmonary Surfactant Spreading on Thin Liquid Films
Advisor: Rachel Levy (Mathematics, email@example.com)
Our group is working to understand the motion of a thin liquid films caused by the presence of surfactants, which lower surface tension. We conduct both wet lab experiments and numerical simulations of a partial differential equations model. The research is motivated by surfactant therapies in premature infants and other pulmonary therapies. The research is also relevant in other biological contexts, such as the tear film of the eye. Our group has recently developed techniques to image surfactant spreading in real time, and we have experiments in progress at HMC and NC State University. We seek funding for a group of 2-3 students to collect data from surfactant spreading and rheological experiments as well as numerical simulations. The research would compare spreading on a Newtonian fluid, such as glycerol, to a shear-thinning fluid such as xanthan gum or a viscoelastic fluid, which would more closely mimic pulmonary mucins. We also plan to explore spreading of DPPC, a surfactant found in the lung, using NBD-PC (a similar surfactant) as a fluorescent tag.
Skills/backgrounds required: experience with quantitative methods (mathematics, computer science, physics) and/or experience in laboratory research (biology, chemistry, physics).Project 14
(Up to 4 students):
What is the neural basis of decision-making?
Advisor: Prof. Glater (Biology, firstname.lastname@example.org)
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.
Skills/background required: Completion of Introductory Biology course. Experience with molecular biology techniques and completion of a Neurobiology course are a plus, but not required. Project 15
Models for Preventing and Treating Malaria in Resource-Constrained Regions
Advisor: Prof. Martonosi (Mathematics, email@example.com)
Malaria is endemic throughout Africa and other regions of the world. While interventions exist to prevent malaria or reduce its consequences, resources for distributing these interventions in developing areas are limited. Since 2012, Prof. Martonosi's research group has been developing an optimization framework for choosing cost-effective allocations of interventions across several geographic regions and multiple time periods subject to budget constraints. Because the use of interventions affects the malaria disease dynamics, this optimization framework relies upon an SIR differential equations model back-end that models how each intervention affects the societal costs associated with the disease. Currently, the model is in need of refinement to more accurately capture the disease dynamics in a computationally tractable way.
- Required: Proficiency in Python
- Required: Exposure to or willingness to learn programming in Matlab
- Required: At least one of the following: Coursework or experience in differential equations modeling beyond the HMC core (e.g. Math 115, Math 180, or relevant courses in mathematical biology); or Coursework or experience in computational mathematics such as numerical analysis or scientific computing.
- Desired but not required: Coursework in optimization techniques such as linear programmingProject 16
Bioreactor Design and Validation for a Tissue-Engineered Cornea.
Advisor: Prof. Orwin (Engineering, firstname.lastname@example.org)
The cornea is the tissue on the front of the eye that provides both structural and optical functions. The goal of this project is to create new corneal tissue using cells and biological structural materials using the native cornea as inspiration. A transparent artificial cornea derived from biological materials is a major challenge in corneal research. Over 10 million individuals worldwide experience bilateral corneal blindness, and corneal transplants are currently the only treatment for restoring vision. Our lab has designed a bioreactor to simulate the forces that exist on native corneal tissue in order to provide this important signal to our growing tissue. Mechanical strain is an important signal that controls corneal cell protein expression. Our existing bioreactor can accommodate up to 6 tissue samples at once, and includes a flow-through media system for sustaining the tissues. Samples are inflated with fluid to varying levels of strain, controlled by a pressure regulator. This project will involve developing a finite-element model of the strain in the tissue sample for various inflation/pressure levels. These results will be validated using experimental results. To determine the strain levels experimentally, we will use a previously validated Matlab based method of quantifying the movements of microbeads in response to pressure changes. In addition, we will work towards Labview control of the media flow system as well as the pressure regulation to induce strain. Project 17
Brain Patch for Traumatic Brain Injury.
Advisor: Prof. Orwin (Engineering, email@example.com)
This project focuses on harnessing regenerative medicine techniques and investigating novel combinations of cell source and scaffold materials to create a cell delivery system (or “brain patch”) for the treatment of traumatic brain injury. Traumatic Brain Injury (TBI) refers to any sudden physical damage to the brain, a condition that affects over 1.4 million people per year in the United States alone. In addition to the limited repair capacity of the damaged brain, secondary inflammatory mechanisms make the initial damage worse by inducing ischemia, hemorrhaging, excitotoxicity, free radical formation, and cell death. Delivering an optimal combination of neural stem cells and stimulatory bioactive factors organized within a supportive extracellular matrix configuration is a promising strategy for neural tissue repair. This project involves developing and characterizing the mechanical stiffness of novel layered scaffolds for the brain patch. Stiffness is an important control factor for determining cell phenotype on the scaffold and it is therefore important to be able to tune the stiffness of our scaffolds. Stiffness will be quantified using mechanical testing equipment and analysis of viscoelastic properties. We have developed a computer program to analyze experimental data to facilitate processing of large amounts of data. In addition, we will quantify antibacterial properties of the new scaffolds as well as the diffusion of various bioactive factors from the scaffolds.Project 18
(Up to 4 students):
Exploring the regulation of transcription by RpoS in E. coli.
Advisor: Prof. Stoebel (Biology, firstname.lastname@example.org)
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 creating a quantitative description of the relationship between the intracellular level of RpoS and transcription from different promoters. These projects involve cloning, western blotting and quantitative RT-PCR. Our goal is to understand how protein abundance and promoter sequence work together to determine patterns of transcription.
In addition, we are using RNAseq to explore how global patterns of transcription respond to changing levels of RpoS. This approach uses high-throughput sequencing to measure levels of transcription of all genes in the genome. We already have one data set in hand, which we will analyze to discover how promoter sequences influence responses to RpoS level across the genome. Depending on progress this summer, we may prepare and sequence additional RNAseq libraries to test further hypotheses about patterns of global gene regulation.
Skills/background required: An interest in these biological questions and a committed, detail-oriented attitude. Molecular biology laboratory experience or computational biology & statistics experience are a plus, but not required. Project 19
Molecular estimation of the octocoral biodiversity of Madagascar
Advisor: Prof. McFadden (Biology, email@example.com)
Tropical coral reefs are the most biodiverse of the world's marine ecosystems, and also one of the ecosystems most threatened by climate change and environmental degradation. Despite their ecological and socioeconomic importance, we still know very little about most of the invertebrate species that inhabit reefs. Estimates of reef biodiversity range over three orders of magnitude and as many as 90% of species may still be undescribed. Octocorals (soft corals and sea fans) are one of the groups of conspicuous, ecologically dominant coral reef species that remain very poorly known taxonomically. Species are difficult to distinguish from one another morphologically, and we do not know the true species-level diversity of many common genera. We have developed a set of molecular markers (a "DNA barcode") that reliably discriminates up to 75% of the octocoral species in reef communities. Using genetic diversity as a proxy for species diversity allows us to estimate the number of octocoral species in coral reef communities and to compare biodiversity across different geographic locations. In this study we will quantify the octocoral biodiversity of Madagascar, located in the western Indian Ocean, and compare the numbers and composition of species found there to reefs in the northern Red Sea (Israel) and western Pacific Ocean (Palau, Taiwan). The project will require extraction of DNA from EtOH-preserved coral samples, PCR-amplification and sequencing of barcode genes, and computation of genetic distances and other measures of species identity.
Skills/background required: Introductory biology and a willingness to learn to use a variety of different, specialized computer programs.Project 20
A computational genomics analysis of hybridization in soft corals
Advisor: Prof. McFadden (Biology, firstname.lastname@example.org)
For many decades, hybridization has been known to play an important role in the evolution of plants. More recently, it has been suggested that hybridization may also be common among corals, but this hypothesis has been difficult to confirm experimentally or genetically. Alcyonium digitatum and Alcyonium sp. A are two closely related species of soft coral that co-occur in Britain. Although these two species reproduce by very different mechanisms, both morphological and genetic evidence suggest that they may occasionally hybridize under natural conditions. We have used next-generation sequencing protocols ("RADseq") to obtain genomic data for both putative parent species, A. digitatum and A. sp. A. This project will involve computational analysis of the genomic data, primarily screening loci across the genome to identify single-nucleotide polymorphisms (SNPs) that distinguish parental species. Depending on time and student interest, DNA libraries will be prepared from putative F1 hybrid individuals to determine if they share SNP alleles with both parent species.
Skills/background: Experience with DNA sequence analysis and basic computer programming skills (python). Ability to adapt existing computational pipelines or develop novel pipelines may be required.Project 21
Characterization of mitochondrial genome evolution in octocorals with compromised DNA repair mechanisms
Advisor: Prof. McFadden (Biology, email@example.com)
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. 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.
Skills/background: Some prior experience with basic molecular biology techniques (e.g., PCR amplification and primer design, cloning) a plus.Project 22
Molecular estimation of the soft coral biodiversity of Dongsha Atoll, Taiwan
Advisor: Prof. McFadden (Biology, firstname.lastname@example.org)
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 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, is now underway, and the goal of this project is to estimate the biodiversity of soft corals from Dongsha for comparison with the more northern Penghu Archipelago as well as other locations in the tropical western Pacific. 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 distance measures to compare the numbers and identities of soft coral species between Dongsha and Penghu. The project will require extraction of DNA from EtOH-preserved coral samples, PCR-amplification and sequencing of barcode genes, and computation of genetic distances and other measures of species identity.
Skills/background required: Introductory biology and a willingness to learn to use a variety of different, specialized computer programs.Project 23
Tissue specific effects of electron transport chain (ETC) Complex I knock-down on lifespan
Advisor: Prof. Hur (Biology, email@example.com)
Although controversies exist, the Free-Radical Theory of Aging remains popular. Here, oxidative damage, such as those inevitably resulting from respiration, is thought to be a major cause of macromolecular damage, deterioration, and eventually, organismal decline. One relatively straightforward means for decreasing oxidative damage may be to reduce the activity of the ETC. Accordingly, previous research has shown that decreasing activity of mitochondrial Complex I, the major entryway of high energy electrons into the eukaryotic ETC is sufficient to increase lifespans in flies (Copeland et al. 2009). In seemingly direct conflict, however, other work has shown that boosting ETC activity can also result in signs of decreased oxidative damage and lifespan extensions (Hur et al. 2013). In this on-going investigation, the student researcher will survey whether novel methods to reduce or boost mitochondrial activity (via reducing or boosting Complex I activity) in tissue specific manners can result in lifespan extensions. In addition, it is not clear what effects increasing or decreasing ETC activity may have with respect to the Free-Radical Theory of Aging, and whether they are indeed conflicting. The undergraduate investigator will also make forays into determining the downstream effects of decreasing and boosting ETC Complex I activity in a tissue specific manner. Part of this work may involve working with collaborators in Prof. David Walker’s lab at UCLA.
Skills/background required: Introductory biology (and lab) or previous molecular biology lab experience, including experience making solutions and sterile technique.
Role of protein homeostasis on lifespan:
Advisor: Prof. Hur (Biology, firstname.lastname@example.org)
Recent studies have shed light on the important role that protein homeostasis plays in aging (Alavez and Lithgow 2012). The specific players, mechanisms, and tissues involved, however, remain largely unknown. The powerful genetics tools available in fruit flies, including those that allow for tissue- and developmental stage-specific expression of transgenes, provides efficient tools to determine the lifespan effects, if any, of manipulating a variety of known pathways involved in protein turnover and homeostasis. During the summer, the student researchers will join in an ongoing survey of the effects on lifespan of manipulating protein homeostatic pathways in a tissue and developmental stage dependent manner. Many projects in multiple states of maturity are available for undergraduate participation, from initially cloning and verifying expression constructs to be used in longevity screens, to developing novel methods to determine effects of tissue specific manipulation of key players in protein homeostasis, to performing survivorship assays to measure the lifespan effects of manipulating specific pathways. Part of this work may involve working with collaborators in Prof. David Walker’s lab at UCLA.
Skills/background required: Introductory biology (and lab) or previous molecular biology lab experience, including experience making solutions and sterile technique.Project 25
Water Uptake by Reptile Eggs
Advisor: Prof. Steve Adolph (email@example.com)
Lizard and snake eggs absorb water from the soil during incubation, and as a result can double or triple in mass over the course of several weeks. Little is known about either the mechanisms or the biological significance of water uptake. The flux of water from the environment into a reptile egg is governed by three factors: (1) the osmotic driving force (determined by the solute concentrations of the aqueous component of the egg); (2) the permeability of the eggshell to water; and (3) eggshell elasticity. Possible laboratory projects for this summer include measuring osmotic and hydraulic components of egg water potential, measuring the mechanical properties of lizard eggshells, making scanning electron microscope images of eggshells, and measuring the permeability of eggshells to water. We will also build and analyze a mathematical model of water uptake using our laboratory parameters.
Skills/background required. Familiarity with basic concepts in ecology and physiology will be helpful. For the modeling component, prior programming experience, preferably in Matlab. Project 26
Matrix Models of Lizard Populations
Advisor: Prof. Steve Adolph (firstname.lastname@example.org)
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.
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 27
Foraging behavior in honey bees
Advisor: Prof. Matina Donaldson-Matasci (email@example.com)Note: Prof. Donaldson-Matasci is not yet at HMC, but will arrive over the summer. The project will begin July 1.
My lab studies the organization of group behaviors in social insects, like ants and honey bees. One area of interest is to understand how communication affects the foraging behavior of honey bee colonies. Honey bees communicate using the famous “waggle dance”, which they use to direct hivemates to the location of specific food resources. This remarkable communication system could make the group more efficient in several ways: (1) bees waste less time searching for resources, (2) bees are preferentially directed to better resources, and (3) bees are directed to short-term resources before they disappear. How important are each of these potential benefits, and how does that depend on the type of environment in which the group is foraging? To explore these questions, this project will focus on the design and testing of artificial food sources that can automatically keep track of foraging visits made by individual bees. This will involve circuit design and programming for microcontrollers equipped with automated sensors, design of 3D printed objects, and troubleshooting in the lab and in the field with live bees.
Skills/background desired: Some electrical engineering and programming experience is required. In particular, knowledge of C or C++ would be particularly valuable, as would any experience with the Arduino platform. Experience with 3D printers is a plus. Creativity, troubleshooting skills, and a willingness to work outdoors (in proximity to flying, stinging insects) are necessary.Project 28
(Up to 3 students):
Neural Control and Biomechanics of Barefoot Running
Advisor: Prof. Ahn (Biology, firstname.lastname@example.org)
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 examine 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 28b (1 student):
Advisor: Prof. Wang (Engineering, email@example.com)
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.
Skills/background desired: CS/engineering students interested in biology and biology students interested in computational methods are welcome, programming experience required.
Project 28c (1 student)
The Effect of Stretching on Drug Transport Across Human Skin
Advisor: Prof. Lape (Engineering)
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 (dead cell) “bricks” 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.
POMONA COLLEGEProject 29
Exploring evolutionary and population dynamics in ciliates via computer simulation
Prof. Andre Cavalcanti, Biology Department
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. My lab is using mathematical modeling and simulations in an attempt to explain the evolutionary pressures that might have led to this organization and its consequences for ciliate evolution. 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.Project 30
Is rab GDI a tumor suppressor gene?
Prof. Cris Cheney, Biology Department
A central theme of our research is the role of vesicle transport in cellular and developmental processes. Vesicle transport is the process where cells move materials in membrane-enclosed vesicles within the cytoplasm. One major vesicle transport pathway in the cell is the endocytosis pathway. Endocytosis involves the uptake of materials from the extracellular environment into vesicles and then movement of these vesicles within the cell. Endocytosis is important for the down regulation of growth signals. Two signaling pathways involved in growth control are the JAK/STAT pathway and the Notch pathway. Rab GTPases are critical for many aspects of vesicle transport, including directionality in transport. Preliminary results in our lab indicate that rab GDP dissociation inhibitor (GDI), a rab accessory protein, may act as a tumor suppressor gene, perhaps through its interaction with rab5 and endocytosis. Pilot experiments indicate that GDI knockdown creates an overgrowth phenotype in Drosophila larval wing disks. Interestingly, a recent report found that two other rab5 accessory proteins may be tumor suppressor genes in Drosophila. This project will quantitate the overgrowth of GDI knockdown disks in Drosophila, by using a GDI RNAi transgene and also by creating mosaic clones of GDI mutant tissue. The goal is to obtain enough data on the extent of overgrowth to create a computational model of overgrowth dynamics. The project will also examine the effect of GDI knockdown on JAK-STAT and Notch signaling, using transgenic fluorescent reporters, image analysis and quantitative fluorescence microscopy. Project 31
Sulfur and iron-based respiration in the deep subsurface
Prof. EJ Crane, Biology Department
Research in the Crane lab focuses on the enzymology and microbiology of sulfur-based and other forms of anaerobic respiration in hot subsurface, deep-sea sediment and hot spring environments. We use molecular biology and computational techniques in bioinformatics to analyze the microbial communities present in these environments to help us understand how a biological system can thrive in a dark, hot (80 °C) petroleum-rich reservoir deep beneath the earth’s surface. We also use analytical electrochemistry to determine the quantity and identity of sulfur compounds being exchanged between these microbes. This work involves collaboration with Matt Sazinsky in the Chemistry Department (determining structures of sulfur-reducing enzymes) and Bob Gaines and Jade Star Lackey in the Geology Department (characterizing iron-based respiration and using mineralogy to detect traces of sulfur metabolism in the geologic record). Summer projects can involve some field work at hydrothermal sites throughout California.. Project 32
Influence of geometry on energy storage/transfer in compact dendrimeric systems
Prof. Roberto Garza, Chemistry Department
Extensive studies have been conducted on the synthesis and general applications of a class of branched molecules known as dendrimers [1-2]. D.A. Tomalia  coined the term”dendrimer” from two Greek words: dendros (tree) that is associated with the shape and meros (part) referring to the chemical structure formed by associated monomers. Among the many uses of dendrimers, one that pertains to this research project is in the context of molecular wires since the branching has shown to improve the efficiency of electron transfer from light-harvesting complexes to energy transfer and storage in artificial antennae . We focus on the energy transfer properties of compact dendrimers and perform numerical simulations using programs such as Maple and Mathematica to consider the lifetime of an energy packet/electron migrating on the dendrimeric structure before being trapped using the theory of Markovian chains. Students will program and run the simulations to look at the efficiency of this energy transfer on different systems: dendrimers, graphenes and nanotubes.
1. A. W. Bosman, H. M. Janssen, E. W. Meijer, Chem. Rev. 99, (1999) 1665.
2. S. M. Grayson, J. M. J. Fréchet, Chem. Rev. 101, (2001) 3819.
3. D. A. Tomalia, H. Baker, J. Dewald, M. Hall, G. Kallos, S. Martin, J. Roeck, J. Ryder and P. Smith (1985) A new class of polymers – starbust-dendritic macromolecules. Polym. J., 17, 117-132.
4. R. Garza- López et al. Asymptotic Scaling for Euclidean Lattices. “Open Range. Nonlinearity across Disciplines.” “Without Bounds: A Scientific Canvas of Nonlinearity and Complex Dynamics.”
Edited by M.G. Velarde. [ Springer-Verlag, 2013 ].
Expanding DESeq to differential expression analysis of two or more conditions for high-throughput data
Prof. Johanna Hardin, Mathematics Department
As the cost of sequencing large amounts of genetic data has drastically reduced since the Human Genome Project was completed a decade ago, sequencing has become increasingly important and widely used. With the advent of new sequencing technologies able to produce vast quantities of data comes the need to develop new statistical and computational techniques to properly sort through and analyze this wealth of information. In the last few years, high-throughput sequencing has become common practice in many experiments and studies. In high-throughput sequencing, the genetic material to be analyzed is cut up into millions of small fragments, which are then sequenced. These sequenced fragments, called reads, are mapped back to the target genome. A common use of high-throughput sequencing is in differential expression analysis, which generally compares the relative expression levels of each gene between different conditions. This analysis uses software packages like DESeq and edgeR to determine whether there is a statistically significant difference in expression levels between conditions for each gene.
Both DESeq and edgeR are designed to deal with exactly two conditions, and when experimenters have three or more conditions they must analyze their results in a pairwise fashion. Because researchers sometimes have more than two conditions to analyze (for example, investigating the expression level of each gene under thrconcentrations of a protein, at 0%, 50%, and 100%), it would be helpful to be able to analyze differential expression across these conditions simultaneously and avoid pairwise comparisons. A simultaneous comparison also avoids multiple comparisons for each gene. Our goal is to generalize DESeq for analysis of differential expression across three or more conditions. (In collaboration with Prof. Dan Stoebel at Harvey Mudd College)
Computer programming to understand impacts of climate change on diving seabirds
Prof. Nina Karnovsky and Prof. Andre Cavalcanti, Biology Department
Prof. Karnovsky and Prof, Cavalcanti are collaborating on studies of seabird diving behavior. Due to climate change, diving seabirds may have to work harder to find their food in certain years and places. Prof. Karnovsky and Pomona students attached TDRs (time-depth recorders) to seabirds in the Arctic and in California to understand changes in their diving behavior. These instruments record pressure (depth) and temperature every 0.5 seconds for up to five days. From these data we can understand how many dives the bird made on a foraging trip, dive depths, dive durations as well as flying and resting time. Until now Pomona students have manually pre-processed these data before using programs Prof. Cavalcanti wrote to summarize diving parameters. This summer, we are seeking students with a strong interest in computer programming and ecology to work with us to 1) create programs that automate the processing of the raw data; 2) make the existing analysis programs more user-friendly; and 3) develop a web interface to make the program available to other scientists.
Raman Spectroscopy of Lipid Bilayers
Prof. Alfred Kwok, Physcis Department
Lipid rafts serve as platforms for signaling proteins. It has been hypothesized that lipid rafts consist of a "liquid-ordered" lipid phase that is enriched in sphingomyelin and cholesterol. The long term goal in my lab is to determine the lipid composition of raft-like lipid domains in model membranes. The specific goal for this HHMI project is to demonstrate that laser-based Raman spectroscopy, which is complement to IR spectroscopy, could be used as an analytical tool to determine the composition of self-assembled lipid bilayer consisting of binary lipid mixtures of POPC and cholesterol. We will first obtain the Raman spectrum from a POPC bilayer and increase the concentration of cholesterol to build a calibration library. We will then use partial least squares regression to determine the composition of a bilayer with "unknown" composition.
Expression, purification, and crystallization of enzymes involved in ascarylose biosynthesis.
Prof. Sara Olson, Biology; Prof. Matt Sazinsky, Chemistry
The ability of pathogens to rapidly develop drug resistance is a major driving force behind the identification of novel therapeutics. An interesting potential drug target is the biosynthetic pathway of ascarylose, a unique and rare dideoxy sugar found only in nematode worms (which infect over 3 billion people worldwide) and some species of gram-negative bacteria (e.g. Yersinia pseudotuberculosis and Pasteurella pseudotuberculosis). Ascarylose is derived from glucose in a multi-step pathway in bacteria, but its formation is not yet understood in nematodes. We have discovered an enzyme that potentially catalyzes the final step of ascarylose biosynthesis in the free-living nematode, C. elegans. This summer, we plan to express, purify, and measure enzyme kinetics to study the putative role of PERM-1 in ascarylose biosynthesis. In collaboration with the Sazinsky lab (Pomona), we will also crystallize the purified protein, collect and process X-ray diffraction data, and model structures of the analogous worm and bacterial enzymes. The structures will serve as a basis for the design of mechanistic inhibitors and/or screening of compound libraries.
The Role of LIGHT/TNFSF14 in the survival and migration of neutrophils
Prof. Melissa Petreaca, Biology Department
Neutrophils are a type of inflammatory cell that, if present in excessive numbers and/or for a prolonged time period, can injure normal tissue, exacerbating the inflammatory response and preventing normal repair processes. In the proposed project, we will use neutrophils isolated from wild type and TNFSF14/LIGHT-/- mice to determine the importance of this cytokine on the survival and chemotaxis of these important inflammatory cells. Cell survival will be quantified using a spectrophotometric cell survival assay, and cells undergoing a form of cell death called NETosis will be identified and quantified using fluorescence microscopy of the chromatin-based “NETs” associated with this process. Neutrophil chemotaxis will be determined by counting numbers of cells migrating in chemotaxis chambers. Results from cell survival, NETosis, and migration assays conducted in wild type and LIGHT-/- neutrophils will be compared to determine any statistically significant differences, which would suggest the importance of LIGHT in these processes.
Design of a novel antimalarial hybrid agent
Prof. Cynthia Selassie, Chemistry Department
The mortality rates of malaria caused mostly by the infectious organism, Plasmodium falciparum (Pf), continue to increase around the globe especially in Africa. The limitations of current drugs coupled with the emergence of Pf resistance to the artemisinins warrant the search for new classes of antimalarial drugs. One of our approaches involves the design and synthesis of bi-functional agents that incorporate two separate, active moieties: one that functions as an inhibitor of dihydrofolate reductase (DHFR) while the other targets an isoform of another enzyme, histone deacetylase (HDAC). DHFR is critical to the synthesis of 5, 10-methylene tetrahydrofolate that acts as a one-carbon depot for the synthesis of dTMP. HDAC plays a significant role in regulating DNA affinity for histones thus controlling transcription levels. HDAC inhibitors prevent the hydrolysis of acetylated lysine leading to dysfunction/deregulation in the plasmodium.
The goal of this project is to synthesize a prototype hybrid inhibitor: 4, 6 –diamino -1, 2-dihydro-2, 2-dimethyl-1-(3’-(4”-N-hydroxyacetamide-anilinomethyl) phenyl-s-triazine. This bifunctional inhibitor with a critical triazine at one end that targets the DHFR pharmacophore will be connected via a hydrophobic linker to a hydroxamic moiety that will interact with the zinc ion in HDAC. This hybrid molecule will be assessed in vitro versus sensitive and resistant Pf. A series of variants of this prototype will be designed and synthesized using the CQSAR software to scan hydrophobic, electronic and steric space. Eventually, quantitative structure activity relationships will be developed to optimize their antimalarial activity and minimize their cytotoxicity to human HL-60 cells.
Mathematical modeling of DNA segregation mechanics
Prof. Blerta Shtylla, Mathmatics Department
Student projects are primarily focused on developing mathematical models that describe how energy is used in order to spatially organize large DNA structures such as chromosomes inside dividing cells. In mammalian cells, this task is achieved with the help of a complex fibrous apparatus called the mitotic spindle, in bacterial cells DNA segregation mechanisms are less well understood. We are now learning that segregation of DNA in bacteria is achieved with the help of a few regulatory proteins that dynamically localize and hydrolyze ATP inside the dividing cell. In this project, students will help with the development of a 2D model that studies the bacterial partition machinery components using in-vitro data. Our goal is to capture the key steps of DNA partitioning and validate or reject diffusion-driven movement as a primary mechanisms for DNA segregation in dividing bacteria.
Skills/background required: Facility with computational programing such as Matlab or agent-based simulation software. Some modeling/partial differential equations and probability background is a plus. Understanding of cell biology enough in order to read and synthesize primary research literature in bacterial cell biology.
Modeling cell mechanics in early C. elegans development.
Prof. Blerta Shtylla, Mathmatics Department
The cytoskeleton of dividing cells is a highly dynamic environment, where multiple components act to mediate the division of the mother cell into two identical daughter cells. Division steps involve some impressive mechanical events at the micron-scale, the underlying mechanisms behind which are not well understood despite the available data. This project is focused on the development of a computational model for the intra-cellular organization of dividing C. Elegans cells. The student will participate by expanding and developing existing code for a computational model that describes the mechanics of DNA reorientation in these cells, and work to calibrate modeling with experimental data. The current code is in C++, so a student that can work in this platform would be particularly well suited. This project is a collaboration with the lab of Adriana Dawes at Ohio State University.
Skills/background required: Facility with computational programing in C++. Some modeling/partial differential equations and probability background is a plus. Understanding of biology enough in order to read and synthesize primary cell biology research literature and data.
Analysis of differential immune response patterns in an AIDS model system
Prof. Sharon Stranford, Biology Department
Our lab uses a mouse model of AIDS (MAIDS) to study genetic and cellular factors that influence susceptibility to acquired immune deficiency. For this we utilize two inbred strains of mice that differ in their susceptibility to immune deficiency following exposure to Murine Leukemia Virus (MuLV). Infection with MuLV results in a chronic and life-threatening AIDS-like disease in one strain (C57BL/6) but only a mild, resolvable illness in the other strain (BALB/c). We study differential responses within the lymphoid tissues of these strains in the first two weeks post infection, prior to the development of MAIDS, for clues to effective antiviral immune response pathways. These studies have involved using DNA microarrays to identify key differential gene expression patterns, along with real time PCR and protein-based assays on individual target genes/proteins. The target genes we are most interested in include members that encode proteins involved in inflammation, apoptosis, digestion and immune suppression. Students will use molecular and/or cellular assays to confirm and quantify the virus-induced differential expression of specific immune-modulating target molecules, comparing disease-susceptible versus -resistant animals.
Exploring Raman Spectroscopy’s Applications in Medical Diagnoses
Prof. Charles Taylor, Chemistry Department
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[1, 2], lung cancer[3-5], 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.
1. Phillips, M., et al., Breath biomarkers of active pulmonary tuberculosis. Tuberculosis, 2010. 90(2): p. 145-151.
2. Phillips, M., et al., Volatile biomarkers of pulmonary tuberculosis in the breath. Tuberculosis, 2007. 87(1): p. 44-52.
3. Fuchs, P., et al., Breath gas aldehydes as biomarkers of lung cancer. International Journal of Cancer, 2010. 126(11): p. 2663-2670.
4. Phillips, M., et al., Volatile biomarkers in the breath of women with breast cancer. Journal of Breath Research, 2010. 4(2).
5. Alfeeli, B. and M. Agah, Micro Preconcentrator for Handheld Diagnostics of Cancer Biomarkers in Breath. 2010 IEEE Sensors, 2010: p. 2490-2493.
6. Solga, S.F., et al., Breath biomarkers and non-alcoholic fatty liver disease: Preliminary observations. Biomarkers, 2006. 11(2): p. 174-183.
7. Phillips, M., et al., Increased breath biomarkers of oxidative stress in diabetes mellitus. Clinica Chimica Acta, 2004. 344(1-2): p. 189-194.
Quantitative Studies of Lipid Adsorption Using Quartz Crystal Microbalance Studies
Prof. Mal Johal, Chemistry Department
The adsorption and fusion of lipid vesicles have been studied extensively using the Quartz Crystal Microbalance. Despite this, little progress has been made in extracting quantitative kinetic and thermodynamic information from the binding curves. This project will explore how pH and ionic strength of the buffer will influence lipid vesicle adsorption and subsequent lysis at the solid hydrophilic-aqueous interface. This work will seek to provide a quantitative description of two key intermolecular interactions (substrate-vesicle and vesicle-vesicle) involved in the bilayer formation mechanism.
Synthesis and Conformational Analysis of Peptide Antibiotics.
Prof. Dan O'Leary, Chemistry Department
The O'Leary lab uses organic synthesis, NMR spectroscopy, and computational chemistry to study conformational interactions within biologically relevant organic molecules. Current efforts are exploring peptide antibiotic analogs of the naturally occurring octapeptide, Temporin SHf:
Students in my laboratory have synthesized six analogs of Temporin SHf, compounds 1-6, which have been tested for antibiotic activity/mammalian cellular toxicity by Professor Ali Ladram, our collaborator in Paris and discoverer of Temporin SHf. Two of our analogs actually outperform the natural product in terms of killing certain bacteria, which is an exciting prospect and has members of our group in pursuit of additional data and new compounds. What remains to be done with compounds 1-6 is to characterize their solution conformation in the presence of SDS micelles (a surrogate for the bacterial cell membrane surface) by a combination of NMR spectroscopy and computational chemistry, as well as identify new unnatural peptide targets for chemical synthesis.
Prof. Wallace Meyer, Biology Department
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: I am looking for an undergraduate who is interested in the conservation of arthropod biodiversity. This undergraduate will work with Meyer in the summer of 2014 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. I would prefer to work with someone who is interested in continuing the project after the SURP is completed.
Learning Objectives: Meyer will teach the student to collect, preserve and identify different arthropod taxa. In addition, the student will 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.
Prof. Tina Negritto, Biology Department
One of the projects in my lab consists on 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.
The effects of urbanization on the herpetofauna of Los Angeles County: a
spatiotemporal analysis spanning the last century (Up to 4 students)
Prof. Kristine Kaiser (Pomona College, firstname.lastname@example.org) and Prof. Lauren Chan (Keck Science Department)
Urbanization leads to myriad changes to the abiotic environment (e.g., increased temperature and noise, altered light regimes, degraded air, water and habitat quality, and modified biogeochemical and hydrological cycles) that have the potential to dramatically affect most species. Some species decline or avoid urban areas (“urban avoiders”), some persist (“urban adapters”) and still others appear to do better in these urban areas (“urban exploiters”). Although many studies have investigated the impacts of urbanization on a single species in a single location, few integrative studies exist. Reptiles make a particularly compelling and tractable study system in Southern California; they are diverse, locally abundant, and easy to work with in the field. We aim to investigate how urban avoiders, adapters, and exploiters differ in behavioral, ecological, and physiological characteristics and in population connectivity. This will be the pilot year of a multi-year project; this summer, we will establish field sites across the Los Angeles Basin, document species distribution and abundance, collect morphometric data, validate physiological and behavioral assays, and identify genetic markers. This project will involve lab work, fieldwork in possibly rough terrain, and travel around Los Angeles County.
Requirements: Introductory biology required. Urban ecology a plus, but not required. Field and lab experience preferred.
Modeling Vortex Rings from Peat Moss
Prof. Dwight Whitaker, Physics Department
In our research group we are analyzing the explosions from Sphagnum moss capsules and their efficacy at dispersing spores. Our previous work has shown that the spores are carried to heights sufficient for wind dispersal by a vortex ring that is initiated by a sudden release of pressurized gas in the sporophyte (Whitaker and Edwards 2010). Our observations, which were published in the journal Science, were the first to observe the creation of vortex rings from a plant. As a next step in our research we are investigating how effectively these vortex rings are carrying their spores. To do this we numerically model the flow fields of the gas that carries the spores using a commercial software package from ANSYS. In the last two years we have run simulations that we compare with high-speed video data of exploding capsules to infer the pressure within the capsule and to characterize the flow field to understand how it drags the spores.
Our current results show that the pressure in the capsules is significantly less than has been previously reported and we are combining this result with morphological analysis done by a group at the Natural History Museum (London) to publish a paper. To complete our analysis a few more consistency tests of our model need to be completed. One interesting consequence of our pressure result is that the modeled vortex rings that most closely match our high-speed video data (Fig. 1) indicate that the vortex rings are suboptimal in that they are not maximizing the impulse to the ejected gas. Currently all vortex rings produced in nature (e.g. from squid, jellyfish, and a healthy human heart) have optimized the impulse to the fluid.
We hypothesize that Sphagnum vortex rings are suboptimal because they are not optimizing the impulse to the fluid, but maximizing the spore launch height to increase fitness. To test this hypothesis we can use a sophisticated dynamical system analysis to find Lagrangian coherent structures (LCS) in the flow field that show regions that carry spores. A robust set of simulation data for flow fields from capsules of different sizes and pressures will be required to examine how the size and shape of the LCSs change and to assess whether the pressure we see is optimal to disperse spores. Once a relation is established for the optimality condition based on spore size, capsule size, and pressure our model can be tested by comparing the launch of spores between species.