2018 Student & Faculty Participants

Student College Major Faculty Sponsor

Sahar Zieba Ahmadi Kresge Applied Physics Ruth Murray-Clay

Yewande Candice Alabi Stevenson Human Biology Melissa S Jurica

Joselyn Garcia Alanzalon Merrill MCD Biology and Economics Camilla E Forsberg

Kennedy Malachi Allen Stevenson Neuroscience Kevin Tyler Hagy

Gabriella Carolina Alvarez Ten Biochemistry Ted Holman

Monica Noel Appiano Stevenson Earth Science Marilou Sison-Mangus

Citlalli Adela Aquino Kresge marine biology Peter T Raimondi

Juan Armas Nine Chemistry Shaowei Chen

Jessica Arozqueta Basurto Crown Neuroscience Bin Chen

Nathan Bamidele Cowell MCD Biology Jeremy R Sanford

Selene Banuelos Kresge Molecular, Cell, & Developmental Biology Doug Kellogg

Rishika Baral Crown Neuroscience Michael D Stone

Zer Barokas Crown Ecology and EvolutionTheresa Rebecca Keates

Rodriel Alcayde Bautista Ten MCD Biology Marilou Sison-Mangus

Alyssa Rose Bercasio Crown Human Biology Camilla E Forsberg

Sarah Rachelle Berman Stevenson Applied Plant Science Ingrid M. Parker

Jacob Samuel Bornstein Stevenson MCD Jeremy Lee

Kristin Bradham Porter CS Paula Schneider

Allyson Marie Capili Cowell MCD Biology Sergio Covarrubias

Emily Isabel Carreno Oakes Earth Science Noah J Finnegan

Akhil Choppa Ten Bioengineering David Lee Bernick

Hana Pak Chuang Stevenson Human Bio Jeremy Lee

James Robert Conklin Porter MCD Biology Jeremy Lee

Carolina Cuellar Stevenson MCD Biology Rebecca M Dubois

Brandon Edwin Acob De Guzman

Crown Human Biology Marilou Sison-Mangus

Zhiqian Deng Crown MCD biology Joshua A Arribere

Thomas Charonnat Dewey Crown Earth Sciences Ana Christina Ravelo

Joshua Ryan Dillen Cowell Chemistry Rebecca M Dubois

Shiron Drusinsky Cowell Neuroscience Jeremy Lee

Sagel Pushpa Ejantkar Ten Human Biology Kevin Tyler Hagy

Emily Jane Ayame Fukano Crown Bioengineering David Lee Bernick

Sabrina Cecilia Riboul Garcia Crown Marine Biology Mark H Carr

Martin Rivera Genova Merrill Ecology and Evolutionary Biology Ingrid M. Parker

Leah Rosemary George Ten Astrophysics, Computer Science Ruth Murray-Clay

Julieta Berenice Gomez Nine Marine BiologyPatrick William Robinson

Lourdes Marcela Gomez Crown marine biology Beth Shapiro

Torrey Raquel Gorra Merrill Marine biology, B. S. Mark H Carr

Joshua S. Gu Ten Bioengineering David Haussler

Yash Gupta Cowell Computer Science Darrell Long

Tim Gustafson Porter Art Kristin Bradham

Sydney Pauline Gutierrez Eight Human Biology Jeremy Lee

Mason Ellis Hargrave Crown Physics and Computational Mathematics David W Deamer

Mckenna Hicks Stevenson Biomolecular Engineering David Lee Bernick

Henry Julian Hinton Merrill BioengineeringMircea S.V. Teodorescu

Melina Midori Huang Xia Stevenson Bioengineering David Lee Bernick

Pratibha Jagannatha Crown Biomolecular Engineering David Lee Bernick

Jessica Maia Jones Stevenson MCD Biology James Ackman

Edward Wonbin Kim Crown MCD Biology / Psychology Kevin Tyler Hagy

Harrison Alan Klinski Eight Human Biology Kevin Tyler Hagy

Conrad Jeffrey Krahling Eight Chemistry David S Kliger

Tari Miriam Kurman Cowell Neuroscience Jeremy Lee

Raul Lara Crown Applied Physics Tuwin Lam

Jamie Casey Lee Oakes Bioengineering David Lee Bernick

Sophie Minnie Lee Nine Molecular, Cellular and Developmental Bi Jeremy R Sanford

Andrea Legg Cowell BS Lindy Caterina Boisvert

Amy Rose Leslie Nine Biochemistry and Molecular Biology Alan Mark Zahler

Erik Ho Mun Li Nine MCD Biology Jeremy R Sanford

Wendy Lin Ten Biology Peter S Weiss

Carmen Ma Eight MCD Biology Susan Strome

Julia Grace Martin Crown Chemistry BS Concentration Biochemistry Glenn L Millhauser

Marin Clement Alix Salomon Mazeres

Merrill Human Biology & MCD Biology Jeremy Lee

Sara Medor Stevenson Biomolecular Engineering David Lee Bernick

Manolo Adrian Mejia Nine MCD Jeremy Lee

Daniel Milshteyn Cowell Bioengineering David W Deamer

Matthew Stephen Modena Oakes MCD Biology Melissa S Jurica

Esther Caridad Munoz Merrill Earth & Planetary Science Chad W Saltikov

Blaise Arman Nasri Stevenson Bioengineering David Lee Bernick

Aisling Lorraine O'Farrell Ten Bioengineering David Lee Bernick

Abigail Joy Ochengco Ten Bioengineering David Lee Bernick

Nanaba Onyinyechi Osae-Brown Porter Neuroscience Jeremy Lee

Norhan Hassan Osman Kresge Astrophysics Ruth Murray-Clay

Rama Ouattara Cowell Biochemistry and Molecular Biology Pradip K Mascharak

Antonia Lynnsey Palu Cowell Molecular, Cellular and Developmental Bi Jeremy R Sanford

Margaret A Pearce Crown Bioengineering Sri Hastuti Kurniawan

Evan Alec Pepper-Tunick Stevenson Biomolecular Engineering David Lee Bernick

Juan Carlos Perez Crown Bioengineering David Lee Bernick

Cassandra Shea Powell Cowell ENVS & BIO Peter T Raimondi

Andrea Ramirez Cowell MCD Biology Alan Mark Zahler

Lucia Judi Rivas Merrill Neuroscience Lindsay Hinck

Kyle Akira Rocha Oakes Physics (Astrophysics) Enrico J Ramirez-Ruiz

Jacquelyn Marie Roger Kresge Bioinformatics Russell Corbett-Detig

Jennie Itzel Ruelas Castillo Crown MCD biology William Sullivan

Dayana Melina Sandoval Crown Biochemistry and Molecular BiologyJeremiah Aaron Tsyporin

Zachary William-Washkevich Schwartz

Crown Chemistry Jin Zhang

Thomas Wayne Schwemberger Merrill Physics Stefano Profumo

Sushmita Sen Cowell Bioengineering David Lee Bernick

Diana Sernas Oakes Mathematics Grant Hartzog

Sajita Caroni Shah-Morales Stevenson Neuroscience/Biomolecular Engineering Yi Zuo

Lynne Sheehan Stevenson Politics Kristin Bradham

Adam J Smith Crown Physics (Astrophysics Jonathan J Fortney

Thomas Miranda Sousa Ten Biomolecular Engineering David Lee Bernick

Samantha Moscardon Stevens Nine MCD Biology Jeremy Lee

Lauren Taniko Strope Stevenson Marine BiologyMonica Mei Jeen Moritsch

Nicholas Barela Tasker Merrill Physics Jonathan J Fortney

Anthony Long Tran Crown Bioengineering David Lee Bernick

Joanna Le Tran Porter Plant Science & MCD Biology Ingrid M. Parker

Thuy-Khanh Tran-Dao Crown Biomolecular Engineering David Lee Bernick

Marcia Trochez Kresge Biochemistry and Molecular Biology Kevin Tyler Hagy

Victor Tse Kresge Molecular, Cellular and Developmental Bi Jeremy R Sanford

Sabrina Chengyu Tsui Crown Computer Science Darrell Long

Alexandra Chloe Turmon Merrill Biochemistry and Molecular Biology Scott Lokey

Natalia Crystal Ubilla Kresge Biochemistry and Molecular biology Kevin Schilling

Valentin Urena Baltazar Oakes Physics Frank G Bridges

Christian Delos Santos Valdez Ten Human Biology, B.S. Marilou Sison-Mangus

Rachel Beth Varnau Porter MCD Bio Grant Hartzog

Joy Velasquez Eight Astrophysics Ruth Murray-Clay

Nitin Vidyasagar Cowell MCD Biology & Literature Jeremy Lee

Carolin Barbara Wahl Crown Chemistry Shaowei Chen

Beckett Elijah Whittier Kresge Biochemistry Carrie L. Partch

Robert Ray Wilcox Crown Neuroscience Jeremy Lee

Ashley Tess Wong Ten Biomolecular Engineering Glenn L Millhauser

Joey Y Wong Oakes Biochemistry and Molecular Biology Jeremy Lee

Clara Kate Zeder Crown Marine Biology Peter T Raimondi

Belle Zheng Merrill Chemistry Peter S Weiss

Adam Lamine Zoubeidi Eight Bioengineering David Lee Bernick

2018 Student Abstracts

BIOCHAR : A TOOL FOR SALT MARSH RESTORATION?Martin Rivera GenovaFaculty Mentor: Ingrid M. ParkerMuch of our coastal salt marsh has been lost or degraded in the last century, compromising important ecosystem services and driving salt marsh restoration projects. One promising method to aid in salt marsh restoration is the addition of biochar, a durable carbonaceous soil amendment which can last underground for years. In agricultural systems, biochar has been proven to increase the size and yield of crop plants under dry, saline conditions by absorbing salts and increasing plant water availability. Biochar application is understudied in salt marsh ecosystems, where biologically stressful salinity and moisture gradients make biochar addition promising. However, biochar effects on plant performance can depend on production, application, and environmental factors. Here, we test the effect of biochar addition on the performance of five native salt marsh plant species at Elkhorn Slough National Estuarine Research Reserve. We transplanted each species in the high marsh, filling holes with plain sand or biochar mix. We conducted monthly survival surveys and bi-monthly growth surveys to assess response, comparing performance in treatment and control groups. This experiment will demonstrate the effects of biochar application rate on salt marsh plant performance and suggest whether biochar addition could improve restoration outcomes in other salt marsh systems.

COMPARING EARTSHINE OBSERVATIONS TO MODELS OF EARTH-AS-AN-EXOPLANETNicholas Barela TaskerFaculty Mentor: Theodora KaralidiDiscovering life on a planet outside our Solar system (an exoplanet) is the Holy Grail for the exoplanet and astrobiology communities. The hunt for life as we know it on exoplanets rests on the characterization of biosignatures in the reflected (and emitted) spectra of Earth-like exoplanets. Our knowledge of these biosignatures naturally comes from what we see of Earth's surface and atmosphere. Observing the earthshine, the sunlight reflected from the Earth to the Moon and back to us, we can observe the Earth as if it were an exoplanet. Using earthshine observations we can study the appearance of biosignatures on the spectrum of exoplanet-Earth. In this study, we compare earthshine observations from the William Herschel Telescope (WHT) with models of the Earth. To model the Earth we use NASA MODIS data for the surface and cloud properties of the Earth on the date which the earthshine was observed. We then use these data as input in a radiative transfer code that model horizontally homogeneous and heterogeneous planets. We will compare both our homogeneous and heterogeneous models with the earthshine data. This comparison could inform the search for habitable exoplanets by showing us what potential signal from an Earth-like planet may look like, and thereby leading to improvements on our models of signals from other worlds.

INVESTIGATION OF THE CENTRAL REGION HISTIDINES ROLE IN THE METAL DRIVEN CIS INTERACTION OF THE PRION PROTEINJulia Grace MartinFaculty Mentor: Glenn L MillhauserThe prion protein (PrP) has been found to cause transmissible spongiform encephalopathies (TSE’s), more commonly know as Mad Cow Disease. PrP’s physiological function is not yet fully known, however it is believed to play a critical role in metal ion homeostasis. Binding one equivalent of Cu2+ to octarepeat (OR) histidine (His) residues drives a cis interaction between the unstructured N-terminus and the structured C-terminus. However, it is uncertain if non OR His residues, which are between the OR and the structured C-terminus, help drive the cis interaction. It was found that when wild type PrP is titrated with up to 3 equivalents of Cu2+, broadening is observed in the peaks of the nuclear magnetic resonance (NMR) spectra. This study investigates how different His mutants affect this broadening as seen in NMR, which can be a measure of the cis interaction. His residues of the central region replaced with tyrosine (H95Y, H110Y, and H95/110Y (DM)) will be tested. Through our investigation, we hope to understand if the His residues of the central region aid in the metal driven cis interaction.

SUBCEREBRAL NEURONAL FATE SPECIFICATION IN THE DEVELOPING CEREBRAL CORTEXDayana Melina SandovalFaculty Mentor: Jeremiah Aaron TsyporinThe cerebral cortex contains different excitatory neurons that are classified based on their projections. Subcerebral projection neurons are found in layer 5 of the cerebral cortex, and project axons to the spinal cord and brainstem. These neurons are affected in neurodegenerative diseases such as ALS, and understanding the molecular mechanisms underlying their generation may reveal some causes for illnesses associated with these neurons. We propose that Sox5 and Fezf2, together, specify subcerebral projection neuron fate. Sox5, a transcription factor expressed in the cortex, is essential for the development of subcerebral projection neurons. Indeed, mice with Sox5 null cortices lack layer 5 Ctip2 expressing subcerebral projection neurons, instead Ctip2 coexpresses with corticothalamic marker TLE4 in layer 6. A transcription factor, Fezf2, which is upregulated by Sox5, specifies subcerebral fate. Here we show that Fezf2 specifies subcerebral neuronal fate post-mitotically using Nex1-Cre conditional Fezf2 knockout mice. These results confirm that Sox5 and Fezf2 are essential for the specification of subcerebral projection neurons.

A PHYSICISTS APPRAOCH TO DARWIN’S “WARM LITTLE POND”Mason Ellis HargraveFaculty Mentor: David W DeamerCycles of biologically relevant reactions are an alternative to an origin of life emerging from a steady state away from equilibrium. The cycles involve a rate at which polymers are synthesized and accumulate in microscopic compartments called protocells, and two rates in which monomers and polymers are chemically degraded by hydrolytic reactions. Recent experiments have demonstrated that polymers are synthesized from mononucleotides and accumulate during cycles of hydration and dehydration, which means that the rate of polymer synthesis during the dehydrated phase of the cycle is balanced (but not dominated) by the rate of polymer hydrolysis during the hydrated phase of the cycle. Furthermore, depurination must be balanced by the reverse process of repurination. Here we describe a computational model that was inspired by experimental results, can be generalized to accommodate other reaction parameters, and has qualitative predictive power

A HIGH-RESOLUTION MG/CA-BASED PLIOCENE SEA SURFACE TEMPERATURE RECONSTRUCTIONThomas Charonnat DeweyFaculty Mentor: Ana Christina RaveloThe Western Pacific Warm Pool (WPWP) is the largest source of heat and moisture to the atmosphere. Even slight changes in the sea surface temperature (SST) of this region can impact Earth’s climate dramatically. Both climate modeling and data-based studies have shown that the WPWP is also sensitive to greenhouse gas (GHG) forcing, however, these studies focus on the Pleistocene, when atmospheric CO2 was generally the same or lower than pre-industrial values. This study reconstructs SST and subsurface temperatures over ~100 kyr during the early Pliocene (~5 Ma) using Mg/Ca of planktonic foraminifera (Trilobatus trilobus and Globorotalia tumida), a reliable paleotemperature proxy. Early Pliocene pCO2 was ~400 ppm, but the climate was likely warmer than present by 1-2 ºC, although discrepancies between data-based studies and models of Pliocene SST has caused debate over WPWP temperatures. Understanding the west Pacific climate during the Early Pliocene is central to predicting its response as global temperatures rise. This study presents Mg/Ca-based SST and subsurface temperature with a 2-3 kyr resolution from IODP Sites U1488 and U1489, and shows that WPWP temperature in the early Pliocene was not warmer than present, confirming other observations. Additionally, ?18O measurements from U1488 indicate the WPWP was more saline than the present, suggesting high local evaporation.

ACCESSORY SIGNALING PROTEINS TO A G-PROTEIN-COUPLED RECEPTOR: EXPLORING THE MELANOCORTIN SYSTEMAshley Tess WongFaculty Mentor: Glenn L MillhauserThe melanocortin signaling system is made up of five class A G-protein coupled receptors (GPCRs) that are responsible for a variety of physiological functions. The melanocortin 4 receptor (MC4R) acts as a key regulator of energy homeostasis by responding to its endogenous ligands, ?-melanocyte stimulating hormone (?-MSH) and agouti-related protein (AgRP), through the cAMP transduction pathway. This stimulation and suppression of cAMP, respectively, follow canonical GPCR signaling mechanisms. However, new research shows that melanocortin signaling cannot be explained through classical agonist/antagonist modulation of MC4R through the G?S pathway. Previous collaborative work by the Millhauser and Cone Labs has shown that there are novel accessory proteins involved in the regulation of MC4R through AgRP and ?-MSH. Namely, Kir7.1 is an inwardly rectifying potassium channel that is modulated by melanocortin ligands through MC4R, which occurs independently of G-proteins. However, the specific mechanism of this novel interaction is not understood and remains largely uncharacterized. The molecular basis of this G-protein independent interaction will be studied using cross-linking and LC-MS/MS, and will help to redefine the melanocortin signaling paradigm. Understanding the melanocortin signaling system and its accessory proteins will aid in the effort to find potent therapeutic treatments for metabolic disease and obesity.

ACCRETION-INDUCED COLLAPSE OF MASSIVE WHITE DWARFSKyle Akira RochaFaculty Mentor: Enrico J Ramirez-RuizAccretion-induced collapse (AIC) of massive white dwarfs (WDs) to neutron stars (NSs) was first proposed in the late 1970’s. Since its inception this mechanism has been used to explain many astronomical events including gamma-ray bursts, Type Ia supernovae, populations of NS in galaxies, and low-mass binary NSs, among other things. Although theoretically well motivated, there are currently no direct observations of AIC events. With limited experimental constraints on the collapse, theoretical research has focused on using stellar evolution codes to determine the important features that affect the collapse. Recent work has shown the importance of minor isotopes in determining the fate of an accreting WD. In an effort to extend our understanding of AIC even further we study AIC in three main steps using the state of the art stellar evolution code Modules for Experiments in Stellar Astrophysics (MESA). We develop a framework for performing more detailed studies of AIC.

ADVANCING AUTOMATION FOR OPTIMIZING LABORATORY AND DATA COLLECTION EFFICIENCYRaul LaraFaculty Mentor: Tuwin LamIn an effort to support the diagnostic calibrations for high energy density physics experiments conducted at the National Ignition Facility and other national laboratories, areas where automation could increase the quality, efficiency, and ease of use of current calibration request and data collection processes were evaluated.

The original process required manual entry of requested services, which included often-lengthy list of measurements to be collected and incorporated into the database structure. This prolonged the request and calibration process and was inherently prone to human error. The proposed solution for the deficiencies included implementing a system that would automate the calibration request process to maximize efficiency and repeatability, and minimize human error.

ANALYSIS OF LOCAL STRUCTURE ABOUT ZN IN ZN DOPED TETRAHEDRITE USING EXTENDED X-RAY ABSORPTION FINE STRUCTURE (EXAFS) SPECTROSCOPYValentin Urena BaltazarFaculty Mentor: Frank G BridgesTetrahedrites are a class of naturally occurring minerals with highthermoelectric efficiency. Thermoelectric materials are needed in devicesaiming to convert heat to electricity directly via the Seebeck effect, andalso for cooling without a refrigerant via the Peltier effect. We examinepure Cu12Sb4S13 and zinc doped Cu10Zn2Sb4S13 tetrahedrite to betterunderstand the metal to semiconductor transition at T~95K in the puretetrahedrite. Understanding why the transition is suppressed upon Zn dopingwill shed light on the structural properties of this material. To probe thecrystal structure, X-ray spectroscopy data at the Zn and Cu K edges werecollected at the Stanford Synchrotron Radiation Lightsource (SSRL). We usethe Real Space X-ray Absorption Program (RSXAP) to analyze the ExtendedX-ray Absorption Fine Structure (EXAFS) region for both the Zn and Cuabsorption edges. The analysis shows that the Zn edge data are more orderedthan the Cu edge data and that Zn substitutes on both the Cu1 sites.

ANTIBACTERIAL MECHANISMS OF GRAPHENE OXIDE QUANTUM DOTSJuan ArmasFaculty Mentor: Shaowei ChenGraphene Oxide Quantum Dots (GOQDs) and reduced GOQDs (rGOQDs) were synthesized using a modified Hummer’s method, and characterized, by high-resolution transmission electron microscopy (HRTEM), X-ray photoemission spectroscopy (XPS), fluorescence spectroscopy, Ultraviolent-Visible light spectroscopy (UV-Vis) and Time-Correlated Single Photon Counting (TCSPC). A light-emitting diode array (LED) at 395-400nm was used to irradiate GOQD and rGOQDs bacterial suspensions to enhance the antibacterial effect of rGOQDs. Colony forming unit (CFU) counts on agar plates were used as antibacterial assays to quantitatively asses the antibacterial activity in dark conditions. The GOQDs and rGOQDs were highly active in the inhibition of bacterial growth with rGOQDs demonstrating the most effective inhibition of Escherichia coli (E. Coli) in liquid media under light irradiation, and GOQDs in the dark. A structure-function relationship is established where Phenanthroquinone-like functional groups are proposed to be the cytotoxic moieties present in GOQDs, likely interfering with the electron transport chain propagation under dark conditions, whereas removal of ketone groups from these species as well as other carbonyl moieties in the GOQD structure through chemical reduction increases the toxicity under light illumination by removing recombination sites. To our knowledge, this is the first time a model has been presented for GOQD and rGOQD cytotoxicity, and can be extended to all carbon nanostructures which will provide a valuable foundation for the development of highly effective carbon-based antimicrobial agents.

ARSENIC BIOGEOCHEMICAL CYCLING UNDER EXTREME, ARCHEAN-LIKE CONDITIONSEsther Caridad MunozFaculty Mentor: Chad W SaltikovAlthough toxic to most life, arsenic can be used by certain microbes in favorable ways to produce cellular energy through oxidation/reduction reactions. Arsenic reduction/oxidation reactions likely evolved within extreme environments, which were abundant on the early Earth during the Archean Eon, 2.5 billion years ago. Searles Lake, located near the Mojave Desert, California, is an Archean-like model system. This salt-saturated, alkaline soda lake has extremely high arsenic concentrations (~4 mM, 22,000 times higher than the As drinking water standard). The project goal is to understand arsenic biogeochemical cycling within extreme environments. Extremophiles are significant due to their unique ability to survive in some of the harshest environments on the planet. In Searles Lake, there is circumstantial evidence that red/purple encrusting biofilms within the sediments host novel photosynthetic microbes that use arsenite as an electron donor. Experiments with light and dark-incubated microcosms using Searles Lake red-hued salt crusts demonstrated the occurrence of anaerobic, light-dependent As(III) oxidation activity. The functional gene for photosynthetic arsenite oxidation, arxA, was detected by PCR from DNA extracted from these microcoms. Current research is focused on metagenomic sequencing and isolating photosynthetic microbes from these microcosms. The results demonstrate that Searles Lake represents an ideal model system for understanding how organisms survive and contribute to arsenic biogeochemical cycling under the most extreme conditions. This work has important implications for comprehending anoxygenic photosynthetic processes that may have occurred during the Archean Eon, over 2.5 billion years ago.

ARTIFICE: A STEGANOGRAPHIC FILE SYSTEMYash Gupta, Sabrina Chengyu TsuiFaculty Mentor: Darrell LongArtifice is a truly deniable steganographic file system which exists in the free space of an existing file system. It can support any arbitrary file system such as FAT32, EXT4, NTFS, etc., and use its free space to hide files.

Encryption is not enough to prevent data from being observable. Encrypted data is still visible, and it opens the possibility of rubber-hose attacks. Artifice breaks up data blocks into chunks, and XOR's each chunk with an entropy source (such as DRM protected media). These chunks are then distributed and written in the free space of the underlying system, thereby preventing an entity to even confirm the existence of said data. Artifice leverages erasure coding and secret sharing techniques to provide reliability of data integrity in case of overwrites from the underlying file system.

Artifice is a Linux kernel module present on a separate, private operating system distributed through a USB drive. This private OS is the only system which has Artifice code. The public operating system does not know about the presence of Artifice. We plan to make Artifice a default driver for the "Tails" distro.

ASSESSING THE EFFECTS OF GONADAL HORMONES ON HEMATOPOIETIC STEM AND PROGENITOR CELLSJoselyn Garcia AlanzalonFaculty Mentor: Camilla E ForsbergHematopoietic stem cells (HSCs) are characterized by their self-renewal and ability to differentiate into all mature blood lineages. As HSCs differentiate they generate multipotent and lineage committed progenitor cells prior to reaching maturity. Since mature blood cells have a limited lifetime, hematopoietic stem and progenitor cells (HSPCs) are responsible for maintaining our blood and immune systems. HSPCs can be found in tissues such as bone marrow and spleen. Clinically, HSC transplantation offers a life-saving treatment to patients who lack their own functional HSPCs. Unfortunately, a sufficient number of HSCs are not always able to be collected for transplantation.

Although efforts have been made to understand what regulates HSC trafficking and expansion, a great deal is still unknown. While there seems to be a limit on the amount of HSCs supported within the bone marrow niche, the splenic HSC niche appears to be more readily adaptable to increases in HSC numbers. Interestingly, our lab previously found that at steady-state, female mice have more HSCs in their spleen compared to males. This suggests the potential for hormonal regulation of splenic HSCs. We hypothesize that either male gonadal hormone production establishes fewer HSCs in the spleen or female gonadal hormone production allows for increased numbers of HSCs in the spleen. We will test this via gonadectomy and hormone replacement. A better understanding of the hormonal regulation of HSCs could improve methods of HSC expansion prior to transplant and increase chances of a successful transplantation.

ASSESSING THE ROLE OF THE P3 PEPTIDE IN ALZHEIMER’S DISEASE PATHOGENESIS USING A DROSOPHILA MODELJoey Y WongFaculty Mentor: Jeremy LeeAlzheimer’s Disease (AD) is a neurodegenerative disease that has been shown to be associated with the amyloid precursor protein (APP). APP is processed in two alternative pathways, an amyloidogenic pathway and a non-amyloidogenic pathway. In both, a series of cleavages produce various peptide fragments, most notably the 42 amino-acid amyloid beta (A-beta) in the amyloidogenic pathway and on the alternative non-amyloidogenic pathway, p3 is produced, which encompasses amino acids 17-42 of A-beta. While A-beta is widely known as a major player in plaque aggregation and AD pathogenesis, it is also crucial to determine the effects of p3 on amyloid formation and its effects on neuron function, as well as how it may differ or resemble A-Beta. This is especially true considering that the p3 peptide is a portion of A-beta and, therefore, may share common characteristics with it. By creating Drosophila that express p3 and comparing them to flies that express A-Beta, using longevity assays and protein assays, we will assess the possible role of p3 in neurodegeneration and how it may interact with, and influence, the neurotoxicity of A-Beta.

ASSESSMENT OF ALIGNMENT SOFTWARE FOR ANALYZING WOLBACHIA ENDOSYMBIONTSJacquelyn Marie RogerFaculty Mentor: Russell Corbett-DetigWolbachia is a bacterial endosymbiont present in many arthropod and nematode species. It has unique abilities to manipulate its hosts’ reproductive systems and has been shown to confer protection against some arboviruses. Scientists have leveraged these phenomena to use Wolbachia as a biological control for decreasing mosquito populations and suppressing disease vectors. We are developing a bioinformatic tool to detect the Wolbachia infection status of arthropod and nematode species. Our tool infers if there is a live Wolbachia infection, no Wolbachia infection, or horizontal gene transfer, which can result from a past Wolbachia infection. The tool requires several alignments, so it’s important that the alignment software we use is high-performing across a diversity of samples and references. To ensure that we use the optimal alignment software in our tool, we profiled alignments using four different reference-based alignment software for two different samples and six different references. Overall, LAST was the highest-performing alignment software.

BIOCHAR: A TOOL FOR SALT MARSH RESTORATION?Martin Rivera GenovaFaculty Mentor: Karen Elaine TannerMuch of our coastal salt marsh has been lost or degraded in the last century, compromising important ecosystem services and driving salt marsh restoration projects. One promising method to aid in salt marsh restoration is the addition of biochar, a durable carbonaceous soil amendment which can last underground for years. In agricultural systems, biochar has been proven to increase the size and yield of crop plants under dry, saline conditions by absorbing salts and increasing plant water availability. Biochar application is understudied in salt marsh ecosystems, where biologically stressful salinity and moisture gradients make biochar addition promising. However, biochar effects on plant performance can depend on production, application, and environmental factors. Here, we test the effect of biochar addition on the performance of five native salt marsh plant species at Elkhorn Slough National Estuarine Research Reserve. We transplanted each species in the high marsh, filling holes with plain sand or biochar mix. We conducted monthly survival surveys and bi-monthly growth surveys to assess response, comparing performance in treatment and control groups. This experiment will demonstrate the effects of biochar application rate on salt marsh plant performance and suggest whether biochar addition could improve restoration outcomes in other salt marsh systems.

BUGS WITHOUT BORDERSPratibha Jagannatha, Thuy-Khanh Tran-Dao, Mckenna Hicks, Thomas Miranda Sousa, Evan Alec Pepper-Tunick, Sara MedorFaculty Mentor: David Lee BernickMuch of the world struggles with inadequate access to essential medicines and nutrition due to high pharmaceutical prices and unreliable distribution. Our solution is to decentralize production of these resources by engineering the edible bacteria, Arthrospira platensis, commonly known as Spirulina, to produce essential medicines and supplements sustainably, photosynthetically, and on-site at healthcare facilities. Due to insufficient research into the genetics of A. platensis, we undertook two separate engineering endeavors in the metabolically similar Synechococcus elongatus PCC 7942 to produce acetaminophen and human usable vitamin B12. As a proof of concept for eventual genetic modification in A. platensis, we sought to insert the genes for acetaminophen production, 4ABH and nhoA, and those for B12 production, ssuE and bluB, into PCC 7942. Within the iGEM time frame, only ssuE was successfully inserted. To aid eventual transformation of these genes into A. Platensis, we also developed a method to create a pure strain of A. platensis UTEX 2340 for whole genome sequencing.

CATIONIC AU(I) COMPLEXES WITH ARYL-BENZOTHIAZOLES AND THEIR ANTIBACTERIAL ACTIVITYRama OuattaraFaculty Mentor: Pradip K MascharakGold has been used for several applications in the past including in dentistry, monetary systems, jewelry, and electronics. Gold has also been used in medicine to treat a wide range of diseases. Recently, gold complexes have shown promising antibacterial effects. Two cationic Au(I) complexes have been synthesized and structurally characterized by X-ray crystallography, namely [(PPh3)Au(pbt)](OTf) (1) and [(PPh3)Au(qbt)](OTf) (2) (where pbt = 2-(pyridyl)benzothiazole, qbt = (quinolyl)benzothiazole, and OTf =trifluoromethanesulfonate). The findings have shown that both complexes have a strong antibacterial effect against the Gram-negative bacteria Acinetobacter baumannii and Pseudomonas Aeruginosa. After examination of reactions with 1 and 2, the results show that cationic Au(I) complexes rapidly cross the bacterial membrane and exert drug action. This likely occurs by disrupting cellular function(s) through binding of cytosolic thiol-containing peptides (such as glutathione) and proteins to the highly reactive (PPh3)Au+ intermediate formed upon in situ dissociations of pbt or qbt.

CHARACTERIZATION OF 79 SPLICING-SENSITIVE DISEASE MUTATIONS IN THE DMD, F8 AND F9 GENES.Antonia Lynnsey Palu, Sophie Minnie Lee, Victor TseFaculty Mentor: Jeremy R SanfordPrecursor messenger RNA (pre-mRNA) splicing is essential for accurate gene expression. Splicing is an important mechanism that controls post-transcriptional gene expression through removing introns and joining exons to form mature mRNA. The spliceosome is a ribonucleoprotein machine that uses cis and trans acting elements to initiate this process. Defective splicing contributes to the pathogenetic basis of disease causing mutations by aberrant mRNA isoforms. Our lab estimated that as many as 26% of missense and nonsense disease-causing interfere with cis-regulatory elements involved in spliceosome assembly (Sterne-Weiler et al. 2011). In this project we tested 79 disease-causing mutations in the F8, F9 and DMD genes. Each of these mutations were computationally predicted to affect pre-mRNA splicing. Using splicing reporter assays we will present evidence that a significant fraction of these mutations induce defective splicing of their exon. Taken together our data suggests that defective splicing may contribute to the etiology of Hemophilia A and B as well as Duchenne’s Muscular Dystrophy.

CHARACTERIZING SPLICING SENSITIVE DISEASE-CAUSING MUTATIONS IN EXON 5 AND 6 OF THE FABRY DISEASE GENE, GALACTOSIDASE A.Erik Ho Mun LiFaculty Mentor: Jeremy R SanfordPrecursor messenger RNA (pre-mRNA) splicing is a critical post-transcriptional process in eukaryotic cells. For each splicing event, the complex cellular machinery known as the Splicesome must assemble onto the mRNA and excise precisely the desired number of bases. This concerted process is regulated by cis-elements within the RNA, such as splicing enhancers and silencers, and trans-elements such as RNA binding proteins. Approximately 10% of all disease-causing mutations affect consensus splice sites sequences, resulting in aberrant pre-mRNA splicing. It is less well understood how mutations affect other splicing regulatory-elements. Recent studies conducted by the Sanford lab and others, suggest that around ~26% of disease-causing missense and nonsense mutations also interfere with splicing regulatory cis-elements (Sterne-Weiler et al. 2011). In this project, we focus on characterizing the molecular impact of mutations within the galactosidase A gene (GLA), which encodes the lysosomal enzyme alpha-galactosidase A. Deficiencies in this enzyme results in Fabry disease, a debilitating disorder which causes kidney disease, heart attack and stroke among other symptoms. Our previous studies identified 34 putative splicing-sensitive mutations within the GLA gene. We found that 15/34 of these sites disrupt important functional elements involved in exon recognition by the splicing machinery.

CHARACTERIZING SPLICING SENSITIVE DISEASE-CAUSING MUTATIONS IN EXON 6 OF THE FABRY DISEASE GENE, GALACTOSIDASE A.Nathan BamideleFaculty Mentor: Jeremy R SanfordPrecursor messenger RNA (pre-mRNA) splicing is a critical post-transcriptional process in eukaryotic cells. For each splicing event, the complex cellular machinery known as the Splicesome must assemble onto the mRNA and excise precisely the desired number of bases. This concerted process is regulated by cis-elements within the RNA, such as splicing enhancers and silencers, and trans-elements such as RNA binding proteins. Approximately 10% of all disease-causing mutations affect consensus splice sites sequences, resulting in aberrant pre-mRNA splicing. It is less well understood how mutations affect other splicing regulatory elements. Recent studies conducted by the Sanford lab and others suggest that around ~26% of disease-causing missense and nonsense mutations also interfere with splicing regulatory cis-elements (Sterne-Weiler et al. 2011). In this project, we focus on characterizing the molecular impact of mutations within the galactosidase A gene (GLA), which encodes the lysosomal enzyme alpha-galactosidase A. Deficiencies in this enzyme results in Fabry disease, a debilitating disorder which causes kidney disease, heart attack and stroke among other symptoms. Our previous studies identified 26 putative splicing-sensitive mutations within the GLA gene. We hypothesize that these sites disrupt important functional elements involved in exon recognition by the splicing machinery.

CODON PARING ANALYSIS IN C.ELEGANSZhiqian DengFaculty Mentor: Joshua A ArribereCodon Paring Analysis in C.elegansZhiqian DengFaculty mentor: Joshua A Arribere

This project is focused on codon pairing bias and how it affects gene expression. Recent research has shown that codon paring is not random. Codon combinations that code for the same two amino acids don’t share equal frequencies in the genome. Data from early research suggests that codon paring affects gene expression. However, the relationship between codon pairing and gene expression remains a mystery.

This project specifically focuses on out-of-frame stop codons that are caused by codon pairing bias. My hypothesis is that out-of-frame stop codons will cause a negative effect on gene expression. In this project I am going to take computational and experimental approaches to test my hypothesis. One is using computational tool to analyze the existent genes, and test if there is a negative relationship between out-of-frame stop codons and gene expression level. The second approach is to experimentally modify a gene with as many off-frame stop codons as possible through silent mutation and analyze the mutant gene expression level compared with the wild type. The data from this project could be helpful to understand the constraints of gene expression which can be applied to synthetic biology to control gene expression by modifying codon pairing patterns.

COMPARING EARTSHINE OBSERVATIONS TO MODELS OF EARTH-AS-AN-EXOPLANETNicholas Barela TaskerFaculty Mentor: Jonathan J FortneyDiscovering life on a planet outside our Solar system (an exoplanet) is the Holy Grail for the exoplanet and astrobiology communities. The hunt for life as we know it on exoplanets rests on the characterization of biosignatures in the reflected (and emitted) spectra of Earth-like exoplanets. Our knowledge of these biosignatures naturally comes from what we see of Earth's surface and atmosphere. Observing the earthshine, the sunlight reflected from the Earth to the Moon and back to us, we can observe the Earth as if it were an exoplanet. Using earthshine observations we can study the appearance of biosignatures on the spectrum of exoplanet-Earth. In this study, we compare earthshine observations from the William Herschel Telescope (WHT) with models of the Earth. To model the Earth we use NASA MODIS data for the surface and cloud properties of the Earth on the date which the earthshine was observed. We then use these data as input in a radiative transfer code that model horizontally homogeneous and heterogeneous planets. We will compare both our homogeneous and heterogeneous models with the earthshine data. This comparison could inform the search for habitable exoplanets by showing us what potential signal from an Earth-like planet may look like, and thereby leading to improvements on our models of signals from other worlds.

CROWDING EFFECTS ON POLY-L-LYSINE REGARDING SECONDARY STRUCTURE INTERMEDIATE STRUCTURE AND TRANSITION THERMODYNAMICSConrad Jeffrey KrahlingFaculty Mentor: David S KligerProtein aggregation and protein misfolding are the cause of many devastating neurodegenerative diseases such as Alzheimer’s, Huntington’s, and Parkinson’s disease. To understand these pathogenic phenomena, the protein folding pathway must first be investigated. In this investigation, circular dichroism (CD) is used to measure the protein folding pathways between different secondary structures of poly-l-lysine (PLL). An inert crowder is added to samples to simulate cellular conditions. By manipulating pH, PLL assumes different secondary structures and by exposing the protein to increasing temperatures, changes in the structure occur.

DAMAGED DNA ENRICHMENT USING BIOTINYLATED CYTOSINESLourdes Marcela GomezFaculty Mentor: Beth ShapiroThe characteristic pattern of cytosine deamination in ancient DNA gives researchers the power to authenticate ancient samples while detecting the presence of modern DNA contamination. Cytosines deaminate to uracils in DNA and we aim to replace these uracils enzymatically with biotinylated cytosines to label and pull down molecules with DNA damage. We expect this will increase the proportion of informative molecules in a DNA sequencing library. Libraries with a higher proportion of informative molecules increases the sequencing power of a single library. We hope this technique will provide a tool for researchers to better study the most poorly preserved specimens.

DARK MATTER FROM PRIMORDIAL BLACK HOLE REMNANTS OF AN EXTENDED MASS FUNCTIONThomas Wayne SchwembergerFaculty Mentor: Stefano ProfumoIt is well established that there is more mass in galaxies than we can see as shown by rotation velocities and gravitational lensing. The most popular explanation is some new form of matter (Dark Matter) which interacts minimally with normal matter. I explore the possibility that Primordial Black Holes (PBH) account for a dominant fraction of Dark Matter under the postulation that Hawking radiation stops for black holes with masses on the order of the Planck Scale (2 ×10^?5?). This possibility is analyzed for several PBH formation mechanisms which produce different initial mass distributions. I test three possible mass functions: monochromatic, log-normal, and a power law. Emphasis is on the log-normal case where I find a sector of parameter space where relics could account for all of the Dark Matter if the distribution is sufficiently narrow and at low enough mass. A monochromatic distribution is allowed provided the mass is less than ?10^9 ?. Power law results are preliminary, but suggest it is possible to produce enough relics with a mass function which dies off fast enough at larger masses.

DESIGNING AN EMG CONTROLLED ASSISTIVE GLOVE FOR THOSE WITH HAND WEAKNESSMargaret A PearceFaculty Mentor: Sri Hastuti KurniawanOf the roughly 795,000 adults who suffer a stroke each year in the United States, a large portion have negative effects in their arms and hands. These effects are typically seen in contractures, where the muscles of the affected arm and hand shorten and stiffen until the person is unable to use the limb. In people with cerebral palsy, the condition can affect the hands and cause grip strength to be very weak. The goal of this research and design project was to create an assistive glove for stroke survivors but was soon extended to include other populations with hand weakness. The ideal glove was to be light, sleek, and comfortable. To create the glove, I designed a control system based on the user's electromyogram(EMG) muscle signals; this allowed the user to control when the glove would open and close to assist in stretching or strengthening. I designed a tendon routing system based on a novel tendon rerouting surgery method which reduced the weight of the glove and protected against overextension of the fingers. I conducted a focus group with people with cerebral palsy to get feedback on the design and use of the first prototype of the glove. This glove, or something like it, could improve physical therapy outcomes in certain populations by being more light, discrete, and comfortable than existing options.

DETECTION OF CANINE C-REACTIVE PROTEIN USING LATERAL FLOW ASSAYAkhil Choppa, Sushmita Sen, Emily Jane Ayame FukanoFaculty Mentor: David Lee BernickA lateral flow assay was built to detect canine C-Reactive Proteins (CRP). CRP is build up of inflammation in the body released from the liver which cause fevers. Normally, the basal level of CRP in most canines is less than 10 mg/L and varies up to 25 mg/L in some canines. However, when a canine becomes sick the concentration of CRP increases by 50 fold or more. In order to determine CRP in canine blood samples, a lateral flow assay was performed. Goat anti CRP were the primary antibodies drawn onto the nitrocellulose membrane as the test line. A solution containing CRP and mAb CRP conjugated to gold particles was mixed and applied to the lateral flow assay to bind to goat anti CRP antibodies. Two different Clones of mAb CRP CGC were used in the lateral flow assay and compared to each other for better detection of CRP. Overall, detection of CRP was seen through mAb CRP CGC Clone 1 and 2. mAb CRP CGC Clone 2 showed better detection. With a working lateral flow assay, there is potential that this technique can identify CRP in canine blood as a medical device.

DO SMALLER GALAXIES PREFERENTIALLY LIVE IN OLDER DARK MATTER HALOS?Sahar Zieba Ahmadi, Norhan Hassan Osman, Joy Velasquez, Leah Rosemary GeorgeFaculty Mentor: Ruth Murray-ClayIt is not well understood why galaxies of the same mass show a range of sizes, and what dark matter halo properties might systematically correlate with this scatter. Using a semi-analytic model of galaxy formation at z=0, we explore an empirical connection between the ages of dark matter halos and sizes of galaxies in narrow bins of stellar mass (from 10^9 to 10^12). We find a weak trend where galaxies in older dark matter halos are smaller on average by ~0.3 decs. This trend itself correlates strongly with both dark matter halo mass (despite controlling the stellar mass) and the mass fraction of stars that were acquired via mergers. In the future, we will repeat our analysis separately for blue and red galaxies, as well as extend it to high-redshift (z~2).

DYNAMIC SOLAR TORNADOES OCCURRING DURING HIGH SOLAR ACTIVITYJoy VelasquezFaculty Mentor: William AtwoodSolar tornadoes are long, linear rotating magnetic untwisting structure features on the Sun’s surfaces. In this study, I observe of series of solar tornadoes occurring during high solar activity, May 20, 2012 through June 30, 2012. The time period of observations was near solar maximum. At the time the active regions were approaching the Sun’s limb, allowing for observations of the tornadoes in profile, were consistent with previous seen studies of on-disk active region solar tornadoes (Wedemeyer, S. et al 2013, ApJ,774:123; and Su, Y. et al 2014, ApJ,785,L2). I observe the solar tornadoes using EUV images from the Solar Dynamics Observatory’s (SDO) Atmospheric Imaging Assembly (AIA). Here, I investigated the dynamic properties of seven different events across the Sun’s disk. All of the selected tornadoes are concurrently visible in 304, 193, and 171 Angstrom images. A group of observed solar tornadoes were unambiguously connected to erupting prominences which is consistent with a different group of tornadoes observed by Wedemeyer, S. et al (2013, ApJ,774:123) and Panesar, N. et al.( 2013, A&A, 549, A105).

EFFECT OF MICROBIOTA AND MERCURY ON DAPHNIA FITNESSBrandon Edwin Acob De GuzmanFaculty Mentor: Marilou Sison-MangusMicrobiota have been found to contribute to the fitness of many different hosts. While microbiome research has revealed the importance of microbiota-host interactions, there has been less research on the role of the microbiome on environmental pollutants, such as mercury (Hg). Hg is a widespread neurotoxin affecting humans and polluting aquatic ecosystems. This study aims to investigate the role of microbiota on host Hg tolerance in the keystone zooplankton species, Daphnia magna. Isolated bacteria from both D. magna CAY (California genotype) and Iinb1 (Germany genotype) clones were tested for Hg tolerance via Minimal Inhibitory Concentration (MIC) assay. Pseudomonas-10, isolate from IinB1 host, was found to exhibit one of the highest Hg tolerance and harbor a putative mercury reductase capable of reducing Hg(II) to gaseous Hg. Before beginning to investigate the role of Pseudomonas-10 on host Hg tolerance, we first verified that Pseudomonas-10 does not kill the host. To do that, axenic D. magna were infected with Pseudomonas-10 and the host’s fitness (survival and fecundity) were compared with bacteria-free and bacteria-supplemented D.magna (daphnids containing parental microbiome over a period of 21 days. D.magna with Pseudomonas-10 was found to survive over the 21-day period. We also determined the Hg tolerance of gnotobiotic hosts (D. magna CAY and IinB1 clones). Five-day old (n=5) Daphnia were exposed to increasing concentration of Hg (0nm, 10nm, 25nm, 50nm, 100nm). Survival was monitored over a 7-day period. While survival of both D. magna CAY and IinB1 clones decreased with increasing Hg, D. magna CAY exhibited higher Hg tolerance when compared to IinB1 for all concentrations. While host genetics likely influence this difference in Hg tolerance in the two different clones, it also suggests that the microbiome of D. magna CAY may also play a role. Currently, we are monitoring D. magna CAY infected with Pseudomonas-10 in the presence of Hg over a 21-day period.

EFFECTS OF AMYLOID-? PRIMARY STRUCTURE ALTERATION ON ALZHEIMER’S DISEASE-LIKE PATHOLOGY IN A DROSOPHILA MODELJames Robert Conklin, Nanaba Onyinyechi Osae-BrownFaculty Mentor: Jeremy LeeAlzheimer’s disease (AD) is the most common form of dementia, with an estimated 44 million people affected worldwide as of 2017. The pathophysiology is characterized by progressive neurodegeneration, leading to memory loss, decreases in cognitive abilities, and changes to personality. The production and accumulation of amyloid-? (A?) protein is a hallmark of the disease. The contribution of A? to the disease state is under investigation. Our study seeks to investigate a sequence variant of A? that has been shown to alter A? aggregates in vitro and therefore may affect its neurotoxicity. We will use transgenic Drosophila to compare the neurotoxicities of the wild type (WT) and variant human A?.

ELECTROSPATIAL ANALOG FRONT END FOR MONITORING OF CEREBRAL ORGANOIDSHenry Julian HintonFaculty Mentor: Mircea S.V. TeodorescuThis study documents the design, implementation, and programming of an analog front end recording system for measuring coordinated biopotential signals produced by cortical organoids. Electrical sensing of action potentials from cells within organoid clusters is usually performed invasively, using microelectrode shanks or patch-clamp nanopipette recording. Invasive probing is problematic because it causes tissue disruption, and significant damage if performed chronically. This system uses noninvasive, gold-plated electrodes to minimize tissue disruption while maintaining sufficient contact distance to record local field potentials from adjacent tissues. Analysis of these recordings, collected from organoids cultured at the Haussler Lab at UC Santa Cruz and the Pollen Lab at UC San Francisco, may permit measuring extracellular field potentials as a proxy indicator for internal developmental activity.

ELM1, ARK1, AND PRK1 KINASES REGULATE THE TORC2-YPK1 SIGNALING PATHWAYSelene BanuelosFaculty Mentor: Doug KelloggCells attune their size to nutrient availability, reducing cell size if proper nutrients are not available. Inactivation of the phosphatase PP2A???¹ causes a loss of this behavior, suggesting that PP2A???¹ plays an important role in cell size regulation. This observation has directed our focus to discovering the molecules that regulate PP2A???¹ and its downstream targets, which include the TORC2-Ypk1 pathway. Using proteome-wide mass spectrometry, we narrowed our search down to several strong candidates including the kinases Elm1, Ark1, and Prk1. In wild type yeast cells, the Rts1 regulatory subunit of PP2A undergoes hyperphosphorylation when cells are shifted from rich to poor nutrients. We revealed that in the absence of Elm1, Ark1, and Prk1 not only did the hyperphosphorylation of Rts1 fail to occur, the typical modulation of cell size and TORC2 signaling in response to poor nutrient availability did not occur. This suggests that Elm1, Ark1, and Prk1 play a role in regulating PP2A???¹ as well as the TORC2-Ypk1 pathway. Future work will seek to map the interaction between the Ark1/Prk1 kinases and TORC2 with the goal of defining the mechanism in which Ark1 and Prk1 regulate TORC2 signaling, and ultimately, cell growth and size.

EXPLORING TRANSPOSABLE ELEMENTS REGULATED BY ZNF649Joshua S. GuFaculty Mentor: David HausslerKRAB Zinc Fingers Proteins (KZNFs) are the largest family of human transcription factors. Many have evolved to battle against transposable elements (TEs) and protect the genome. When TEs are not repressed, they can disrupt genes and cause diseases. Throughout evolution, different KZNFs have emerged to battle invading TEs, leading to primate specific KZNF-TE interactions. I investigated different families of transposable elements that were regulated by a specific KZNF, ZNF649. By analyzing ChIP-seq data of KZNFs and transposable elements, nucleotide KZNF recognition motifs were calculated and validated experimentally. With a binding reporter assay, I discovered that ZNF649 represses the TE L1PA4. Additionally, I showed how specific nucleotide mutations in the calculated ZNF649 DNA recognition motif are vital for ZNF649 to repress L1PA4.

To study other TEs that ZNF649 may have regulated, I tested to see if ZNF649 repressed the TE SVA, since it bound the VNTR region of SVA in the ChIP-seq data. Furthermore, I used CRISPRi to knockdown ZNFs and study the change in expression levels of the ZNF and the TE it regulates. I determined the molecular requirements for ZNF649 to repress TEs, which includes the required nucleotides of the recognition motif and finger protein domains that recognize the motif, leading to the repression of the TE by ZNF649. Finally, I created a large KZNF library, which established a powerful platform to study how KZNF-TE interactions have influenced human-specific biology. My study will help identify new KZNF-TE interactions and elucidate the relationships between ZNF649 and the TEs it regulates.

EXPRESSION OF THE HUMAN ANTIMICROBIAL PEPTIDE, LL-37, MODULATES THE NEUROTOXICITY OF A?42 IN A DROSOPHILA MODEL OF ALZHEIMER'S DISEASETari Miriam Kurman, Sydney Pauline GutierrezFaculty Mentor: Jeremy LeeAlzheimer’s disease (AD) is a progressive neurodegenerative disease affecting more than 44 million people worldwide. AD is the most common form of dementia, and can lead to cognitive impairment, memory loss, and changes in behavior. AD is characterized by an accumulation of plaques composed of amyloid-beta (A?) peptide and intracellular neurofibrillary tangles. Recent evidence suggests that the 42-amino acid A? peptide, A?42, may function as an antimicrobial peptide (AMP), and may also interact with other AMPs.

LL-37, the human cathelicidin AMP, functions in the innate immune system to inhibit bacterial agglutination to host cells. Recent studies have shown that LL-37 can bind A?42 in vitro, inhibiting the formation of A?42 fibrils and plaques. Research suggests that A?42 plaques are neurotoxic; as such, LL-37 could affect A?42’s neurotoxicity. We initially investigated these affects through a longevity assay, which showed that the A?42-mediated deficits in lifespan are partially rescued by A?42-coexpression with LL-37. We are now assessing the levels of A?42-gene expression using qRT-PCR. Additional experiments will be conducted to assess the mechanism of interaction between LL-37 and A?42, as well as into the possible affects of A?42 on larval and pupal development.

EXPRESSION PATTERN OF GLI1 AND EFFECTOR OF SONIC HEDGEHOG PATHWAY IN THE DORSAL CORTEXJessica Arozqueta BasurtoFaculty Mentor: Bin ChenNeuronal stem cells (NSC) generate both neurons and glial cells. During development, radial glial cells (RGCs), the embryonic NSCs, sequentially generate different neural and glial subtypes in the cerebral cortex. Our previous paper showed that Fezf2+ RGCs generate glutamatergic cortical projection neurons. We discovered that Fezf2+ RGCs also generate olfactory bulb (OB) interneurons at embryonic and early postnatal stages. Recent publications showed that OB interneuron shared their origin with embryonically born neurons and glia. These studies indicated that there is a transition of radial glial cells from generating cortical excitatory neurons to olfactory bulb interneurons. But the molecular mechanism regulating this switch is unknown. Gsx2 has been shown to be required for OB development. We hypothesize that Gsx2 is involved in RGCs making a switch of generating cortical projection neurons to OB interneurons. In addition, it is known that NSCs and their progenitors control early brain development via a signaling transduction cascade, one of which is achieved through the sonic hedgehog (Shh) signaling pathway. In the central nervous system (CNS) there is a graded concentration of Shh that causes the activation or repression of transcription factors (TFs) via translocation of an activated form of Gli (Gli-A) in the nucleus, where induction of target gene Gli 1 is activated. This process results in specification of particular brain regions. Here we show Gli1 LacZ as a downstream regulator of the Shh pathway.

HEMATOPOIETIC STEM CELL TRAFFICKING ACROSS BONE MARROW NICHE IS REGULATED BY ROBO4Alyssa Rose BercasioFaculty Mentor: Camilla E ForsbergEngraftment of hematopoietic stem cells (HSCs) plays a vital role in HSC transplantation therapy, but the mechanisms behind the trafficking of these cells are still not completely understood. By clarifying the mechanisms of HSC trafficking, improvements can be made to current HSC transplantation therapies.The Forsberg Lab has previously shown that the transmembrane receptor, ROBO4, plays a role in the trafficking of HSCs into and out of the bone marrow. HSCs transplanted into a ROBO4 deficient (R4 -/-) host exhibit lower engraftment of HSCs in the bone marrow than that of a WT host. R4-/- hosts have poorly developed bone marrow sinusoidal endothelial cells (SECs), with significantly lower vascular cell adhesion molecule (VCAM1) expression on SECs. VCAM1 is a marker involved in blood cell trafficking. Furthermore, short-term homing assays in R4-/- hosts indicated perturbation of HSC trafficking in the sinusoidal niche. In this study, we use a modified short term homing assay to examine the morphological effects of transplanted hematopoietic stem and progenitor cells (HSPCs) into R4-/- hosts against WTs, in order to understand if these cells are blocked from engraftment due to ROBO4 deficiency.

HYBRIDIZATION ASSAY FOR VIRAL DNA, VISUALIZED BY MICROBEAD AGGREGATIONAbigail Joy Ochengco, Jamie Casey Lee, Anthony Long Tran, Melina Midori Huang XiaFaculty Mentor: David Lee BernickToo often, viral pandemics such as Ebola, Polio, and Zika are difficult to contain due to the lack of accessible resources needed for detection of infectious viruses. Therefore, early detection mechanisms are essential for prevention and containment of pathogenic viruses. With this project, we aim to design an early diagnostic test for presence of viral DNA that produce rapid results with a central compass on emphasizing the low-cost production and portability. The focus of this project are mycobacterium phages whose host is Mycobacterium smegmatis (M.smegmatis) which is BioSafety Level 1 classification. Bacteriophages are viruses that infect and kill bacteria by inserting its genome into the bacteria to be replicated, the replication of bacterial genome is halted and therefore the bacteria consequently are destroyed. This project aims is to design an assay to detect the presence of the mycobacterium phage cluster T whose conserved tape measure gene sequence is utilized to design a synthetic oligonucleotide capture and reporter probes. Qualitative visualization of target DNA sequence bound to the assay through aggregation of microbeads are visualized under microscope. The long-term follow-up of this project is to make virology research more accessible by developing a system to isolate, detect, and analyze viral DNA presence in a sample for studies in non-traditional laboratory settings.

IDENTIFICATION OF BIASES IN MARINE TERRACE GLOBAL DATABASE USED AS PROXY FOR COASTAL UPLIFT RATESEmily Isabel CarrenoFaculty Mentor: Noah J FinneganMarine terraces are coastal landforms which form as a consequence of the relative motion between coastal rock uplift and changes in sea-level during glacial-interglacial cycles. These landforms can be preserved over time as paleoshoreline sequences and reflect coastal dynamics along actively uplifting margins. For this research project, I am working with an extensive global database compiled by Pedoja et al. (2014) which contains over 900 identified paleoshoreline sequences. The compilation is used, in bulk, by the authors to describe global tectonic uplift of the coasts in the last 100 kyr. I am testing whether inherent biases in the marine terrace record and its sampling affect their conclusions. More specifically, I am investigating whether marine terraces are best created and preserved in an optimal uplift rate window that would bias the entire record. My results thus far indicate that the global record is skewed by intensely-studied sites such as the Japanese Islands. After correcting for sampling proportions, I find that 60% of the marine terraces recording uplift rates in a spectrum between -0.5 and 8 mm/yr fall in a narrow range between 0.1 and 0.5 mm/yr, regardless of the tectonic setting at active margins. This suggests that paleoshorelines might be best preserved in an optimal window of uplift rates. Next stages include comparing the marine terrace uplift record with an independent database. Strong discrepancies between two uplift proxies would support the hypothesis of inherent bias in the marine terrace record.

IDENTIFYING WOLBACHIA EFFECTORS IN S. CEREVISIAE BY AFFECTING TY EXPRESSIONDiana SernasFaculty Mentor: Grant HartzogWolbachia pipientis is a bacterium that infects about 70% of insects globally as well as several nematodes implicated in human diseases. Atypical for bacteria, Wolbachia intracellularly infects hosts intracellularly and is vertically transmitted through the maternal germline. Wolbachia influence the reproductive success of its hosts in favor of infected individuals ensuring an increasing spread of Wolbachia in each population. Previous work suggests Wolbachia achieve their reproductive advantage by distorting the host’s cell chromatin packaging. By taking a molecular genetic approach, we can identify Wolbachia proteins that manipulate a host’s reproduction. We are introducing a Wolbachia DNA expression library into S. cerevisiae to screen for phenotypes previously associated with altered chromatin structure, gene expression, and chromosome segregation. Specifically, the Suppressor of Ty (Spt-) phenotype. Ty elements are retrotransposons found in the S. cerevisiae genome. When inserted in or near a gene, it may incorporate new initiation sites, thereby shifting both start sites and structure of transcription. For example, Ty elements at the 5’ end of HIS4 and LYS2 lead to His- and Lys- phenotypes. Prior studies have shown that mutated genes encoding aspects of chromatin and transcription machinery induce Spt- phenotypes, in this case, His+ and Lys+ phenotypes. Because transcription machinery, histones, and other chromatin components are highly conserved in eukaryotes, we hypothesize that Wolbachia proteins altering transcription or chromatin in S. cerevisiae may also be altering their host organisms.

INFLUENCE OF MICROBIOTA ON IMMUNOLOGICAL RESPONSE IN PASTEURIA-INFECTED DAPHNIA MAGNAChristian Delos Santos ValdezFaculty Mentor: Marilou Sison-MangusNumerous links have been made connecting microbiota to the onset of certain disease in human health (6, 7). Because of the limitations in testing these hypotheses in humans, research relies on model organisms to elucidate these connections. Elucidating these connections of Daphnia pathogen resistance to its microbiota will reveal insights about the dependencies of a host to its bacterial network. How the microbiota modulates the immunological response of the Daphnia model organism is important in understanding the significance of a host microbiota.We hypothesize that removing the microbiota of Daphnia will have an adverse effect on the animal’s resistance to its natural parasite P. ramosa. We further hypothesize that different compositions of microbiota will have varying effects on the animal’s resistance.Our lab has previously shown that in the crustacean model system Daphnia, bacteria-free hosts exhibited decreased fitness in terms of body sizes and high mortality (3). We observe the effect that microbiota has in modulating the immunological response of Daphnia magna by culturing sterile Daphnia and infecting with the obligate parasite P. ramosa. We do this using established methods from this lab. We report the differences in terms of fecundity and phagocyte count.

INITIAL ASSOCIATION OF U2 SNRNP WITH AN INTRON IS INDEPENDENT OF ATP HYDROLYSISYewande Candice AlabiFaculty Mentor: Melissa S JuricaPre-mRNA splicing is an essential component of gene expression. Splicing is a process that removes non-coding regions (introns) and ligates the flanking coding regions (exons) into mRNA which can then be translated into proteins that have a multitude of functions in the cell. The spliceosome is the molecular machinery responsible for this process. ATP is required for the dynamic step-wise assembly and rearrangements of components of the spliceosome. Some of the proteins that make up the spliceosome use the energy of ATP hydrolysis to break existing RNA–RNA interactions to allow the formation of new ones.

The goal of this project is to determine structural and mechanistic features of early-assembled spliceosomes. Specifically, we want to understand the role of ATP in the initial association of U2 snRNP with an intron. To examine this, we designed a pre-mRNA substrate predicted to form a stable complex with U2 snRNP. I then analyzed complex assembly in cell extracts via native gel analysis. Preliminary results suggests that early association of the U2 snRNP with the pre-mRNA is dependent on the presence of ATP, but not its hydrolysis. Going forward, I will use RNA crosslinking experiments to confirm the presence of U2 snRNA in early assembled complexes. Taken together these experiments will reveal the structural basis for stable U2 snRNP association and early spliceosome assembly.

INVERTEBRATE-ALGAL ASSOCIATIONS IN ALASKA: AN EXPLORATION INTO HOW STRONGYLOCENTROTUS DROEBACHIENSIS AND HALIOTIS KAMTSCHATKANA INTERACT WITH THE ALGAE THEY CONSUMECassandra Shea Powell, Clara Kate ZederFaculty Mentor: Peter T RaimondiGrazers are ecologically important species in kelp forest systems and their interaction with the algae that they consume is a factor that determines the health of the ecosystem they inhabit. This study evaluates two key grazer species, Strongylocentrotus droebachiensis and Haliotis kamtschatkana, at the northern edge of the Macrocystis pyrifera kelp forest range in Sitka, Alaska to determine how this interaction plays out. We performed a series of field surveys and lab experiments to understand four key components of this relationship: what these grazers are associated with in the field, what potential food types are available in the habitat, what type of algae is being consumed, and if given a choice, which algal type is most preferred. S. droebachiensis were found to be associated with encrusting brown algae at a higher rate than the field availability and showed a strong preference for M. pyrifera in both the field and lab. H. kamtschatkana were found to be associated with crustose coralline algae, but preferred to eat a species of brown algae, Agarum clathratum. These results shed light on the different types of interactions grazers can have with their habitat and allow us to understand how the system is shaped by these species.

INVESTIGATING A-ETA-ALPHA'S ROLE IN ALZHEIMER'S DISEASEEdward Wonbin Kim, Samantha Moscardon StevensFaculty Mentor: Jeremy LeeA hallmark of Alzheimer’s disease is plaques of oligomerized amyloid-beta (A?), a peptide product from sequential cleavage of membrane-bound amyloid precursor protein (APP) by beta and gamma secretases. While it is widely accepted that A-beta is the primary pathogenic agent of Alzheimer’s disease, recent research suggests alternative products of APP processing also play important roles in Alzheimer’s disease pathogenesis. One recently identified product, amyloid-eta-alpha (A?-?), has been found to be neurotoxic in vitro (Haas et al., 2015). APP processing pathways seem to exist in equilibrium; inhibiting beta-secretase in order to reduce A? results in increased A?-? levels. The goal of this study is to investigate A?-?’s neurotoxicity and pathological role in vivo in an Alzheimer’s disease model. To accomplish this, we are generating a gene construct to express A?-? in neurons of D. melanogaster (fruit fly) using the Gal4-UAS system. We will assess the neurotoxicity of A?-? as measured by longevity and behavioral assays. A?-?-expressing flies will be cross-bred with A?-expressing flies to investigate the effect of A? and A?-? co-expression on Alzheimer’s disease like pathology. The findings of this study may provide a more complete model of Alzheimer’s disease pathogenesis, and inform the development of effective treatments and prevention methods by providing evidence for A?-?’s role in Alzheimer’s disease.

INVESTIGATING HOW PER2 INTERACTS WITH CLOCK:BMAL1 TO UNDERSTAND CIRCADIAN RHYTHMSBeckett Elijah WhittierFaculty Mentor: Carrie L. PartchMolecular clocks are cellular complexes that keep track of time within cells, and control approximately 40% of our genome. They regulate gene expression and physiology in ways that influence how some diseases, including cardiovascular disease and cancer, manifest and progress in different individuals at different times of the day. Deciphering how circadian rhythms work at a molecular level will help us understand how they influence our physiology, and could help us develop treatments for associated diseases in mammals.The main driver of circadian rhythms is a transcription-based feedback loop that completes a cycle about every 24 hours. This negative feedback loop uses PER and CRY proteins, whose genes are targeted by CLOCK:BMAL1, to repress the circadian complex. Our aim is to understand how PER2 interacts with CLOCK:BMAL1 at a molecular level. Co-immunoprecipitation experiments show that CRY:PER:CLOCK:BMAL1 form a complex, but the molecular details of this interaction remain elusive. We determined that PER2 makes direct contact with CLOCK:BMAL1 and may stabilize interactions between CRY1/2 and CLOCK:BMAL1. Our preliminary data shows the CRY-binding domain (CBD) of PER2 interacts with the CLOCK:BMAL1 complex. We are using a fragment-based approach to map the portion of the PER2 CBD that is relevant for binding CLOCK:BMAL1. Understanding where and how PER2 interacts with CLOCK:BMAL1 will help us understand how this stabilization occurs, and how PER2 contributes to repression.

INVESTIGATING MITOCHONDRIAL TRANSPORT DEFICITS IN ALZHEIMER'S MODEL DROSOPHILAShiron Drusinsky, Robert Ray Wilcox, Nitin Vidyasagar, Marin Clement Alix Salomon MazeresFaculty Mentor: Jeremy LeeAlzheimer’s disease (AD) is broadly defined by dementia and its primary pathogenic agents are widely considered to be the neurotoxic proteins Aß and Tau. Mitochondrial transport deficits are believed to play a pivotal role in the development of AD, ostensibly as a consequence of Aß and Tau toxicity; however, this has not been thoroughly demonstrated in humans nor animal models of AD, and the mechanisms by which Aß and/or Tau might compromise mitochondrial transport remain elusive. Mitochondrial transport functions as a crucial mechanism by which neurons deliver mitochondria to energy deficient regions along their extended axons and return dysfunctional mitochondria to the cell body for turnover, and is implicated as a mechanism for aging and neurodegeneration. It is therefore imperative to study mitochondrial transport dynamics in the pathophysiological context of AD, but limitations in animal models have precluded researchers from studying mitochondrial transport non-invasively and throughout the aging process. In this study, we will use the flat and translucent Drosophila wing as a model for studying mitochondrial transport in aging, AD model neurons. Our results will confirm whether mitochondrial transport deficits arise in AD model Drosophila, and if so, we will go on to elucidate the mechanisms by which these deficits might develop.

INVESTIGATING PROTEIN EXPRESSION PATTERNS OF THE EPIGENETIC GERMLINE REGULATOR MES-4 IN C. ELEGANSCarmen MaFaculty Mentor: Susan StromeThe oocyte provides the embryo with proteins that specify cell identity through epigenetic regulation. The mechanisms by which maternally provided epigenetic regulators specify cell identity are not well understood. In Caenorhabditis elegans (C. elegans), the maternally loaded epigenetic regulator Maternal Effect Sterile-4 (MES-4) is crucial for specification of germ identity and formation of a germline. Previous work in the Strome lab showed that MES-4 is required for ectopic expression of germline traits in some somatic cells of DRM mutant worms, suggesting that MES-4 may be expressed in and confer germline potential to some somatic tissues. To understand how MES-4 confers germline potential to somatic cells, it is important to determine which somatic cells express MES-4 during development. I live imaged transgenic worms that express MES-4 fused to Green Fluorescent Protein (GFP) (mes-4::gfp engineered into the endogenous locus) using confocal microscopy. My imaging showed that MES-4 is localized in germ cells at all stages and in some somatic cells at embryonic and early larval stages. Based on tissue maps, I speculate that the somatic cells that express MES-4 in larvae are seam cells, one of the few somatic cell types that undergoes stem-cell-like divisions during larval development. These findings suggest that MES-4 expression is not exclusive to the germline, but may instead be broadly linked to cells capable of stem-cell-like proliferation. Maternally provided MES-4 is critical for the primordial germ cells in embryos to form a functional germline, and embryonic expression is not sufficient for germline development. To gain insight into when MES-4 likely functions, it is important to analyze how long maternal MES-4 persists and when synthesis of new MES-4 from the zygotic genome starts. I performed genetic crosses to generate embryos that allowed me to distinguish embryo-expressed GFP tagged MES-4 from untagged maternal MES-4. Using live imaging, I detected embryo-expressed MES-4::GFP in mid to late stage embryos, suggesting that maternal MES-4’s essential activity to promote germ cell fate is very early in embryo development. Determining where and when MES-4 is expressed will provide insight into how MES-4 functions to drive germline identity, which will enhance our understanding of how maternally provided factors and epigenetic regulators drive proper development.

INVESTIGATING PROTEIN EXPRESSION PATTERNS OF THE EPIGENETIC GERMLINE REGULATOR MES-4 IN CAENORHABDITIS ELEGANSCarmen MaFaculty Mentor: Susan StromeThe oocyte provides the embryo with proteins that specify cell identity through epigenetic regulation. The mechanisms by which maternally provided epigenetic regulators specify cell identity are not well understood. In Caenorhabditis elegans (C. elegans), the maternally loaded epigenetic regulator Maternal Effect Sterile-4 (MES-4) is crucial for specification of germ identity and formation of a germline. Previous work in the Strome lab showed that MES-4 is required for ectopic expression of germline traits in some somatic cells of DRM mutant worms, suggesting that MES-4 may be expressed in and confer germline potential to some somatic tissues. To understand how MES-4 confers germline potential to somatic cells, it is important to determine which somatic cells express MES-4 during development. I live imaged transgenic worms that express MES-4 fused to Green Fluorescent Protein (GFP) (mes-4::gfp engineered into the endogenous locus) using confocal microscopy. My imaging showed that MES-4 is localized in germ cells at all stages and in some somatic cells at embryonic and early larval stages. Based on tissue maps, I speculate that the somatic cells that express MES-4 in larvae are seam cells, one of the few somatic cell types that divide a few more times during larval development. These findings suggest that MES-4 expression is not exclusive to the germline, but may instead be broadly linked to cells capable of proliferation. Maternally provided MES-4 is critical for the primordial germ cells in embryos to form a functional germline, and embryonic expression is not sufficient for germline development. To gain insight into when MES-4 likely functions, I determined when during embryogenesis worms begin to newly synthesize MES-4 from the zygotic genome. I detected embryo-expressed MES-4::GFP in mid to late stage embryos, suggesting that maternal MES-4’s essential activity to promote germ cell fate is very early in embryo development. Determining where and when MES-4 is expressed will provide insight into how MES-4 functions to drive germline identity, which will enhance our understanding of how maternally provided factors and epigenetic regulators drive proper development.

INVESTIGATING THE AGING EFFECT OF 3-AMINOPROPYLTRIETHOXYSILANE IN PEROVSKITE SYNTHESIS AND CHARACTERIZATIONZachary William-Washkevich SchwartzFaculty Mentor: Jin ZhangIt is projected that world energy consumption will rise 28% by 2040. More sustainable and abundant energy sources such as solar are currently being investigated as a means to fulfill the world’s energy demands. The majority of solar cells are composed of silicon due to the material’s high efficiency and extended lifetime. However, the high production cost of silicon solar cells have led researchers to look for alternative materials. Perovskite nanoparticles are being considered as a promising alternative because of a tunable band gap, slow recombination time in ambient light, high power conversion efficiency and inexpensive cost to produce.This study is focusing on improving the reproducibility of perovskite nanoparticles. Previous synthesis of perovskite nanoparticles using oleic acid and 3-aminopropyltriethoxysilane (APTES) as capping ligands resulted in particle size inconsistency attributed to age of APTES. Because optical properties have a large dependence on particle size, variations in emission spectra additionally indicated particle size non-uniformity. Aging of APTES in an aerobic environment has shown a red shift in emission over time. This is due to a partial hydrolysis and condensation of APTES, which leads to the formation of cross linked siloxane bonds that increase the size of the branched capping ligand. Future work involves the investigation of the aging effect of APTES in an anaerobic environment as a means to verify the role of oxygen in formation of cross linked siloxane bonds and development of a method to characterize aged APTES aliquots.

INVESTIGATING THE ACTIVE SITE OF HUMAN PLATELET-TYPE 12-LIPOXYGENASEGabriella Carolina AlvarezFaculty Mentor: Ted HolmanLipoxygenases (LOXs) are the ubiquitous metalloenzymes that metabolize polyunsaturated fatty acids in the body. Human LOXs are classified into three major categories: 5-, 12- and 15-LOX. The product of 12- Lipoxygenase specifically has been implicated in diabetes, cardiovascular diseases, cancer and many kidney diseases. Drug development against this enzyme is lagging behind other members of the oxygenase family as the 3D structure of this enzyme has not been solved. Understanding the interaction of 12-LOX with arachidonic acid and characterizing its binding is crucial for developing an inhibitor that is both potent and specific. Studies of 15-1 Lipoxygenase revealed three areas of interest where pi-pi interactions, ionic interactions and enzyme specificity were identified. The present study tests the three-point interaction hypothesis in 12-LOX by utilizing site-directed mutagenesis.

INVESTIGATING THE P3 PEPTIDE IN ALZHEIMER'S DISEASE USING A DROSOPHILA MODELJoey Y WongFaculty Mentor: Jeremy LeeAlzheimer’s Disease (AD) is a neurodegenerative disease that has shown to be associated with the amyloid precursor protein. Processed in two alternative pathways, an amyloidogenic and a non-amyloidogenic, a series of cleavages produce various peptide fragments; most notably the 42 amino-acid amyloid beta (A-beta) and on the alternative path, p3, which encompasses amino acids 17-42 of A-beta. While A-beta,is widely known as the major player in plaque aggregation and AD pathogenesis, it is also crucial to determine the effects of p3 on neuron function and how it many differ or resemble that of A-Beta. This is especially true considering that the p3 peptide is a portion of A-beta and therefore may share common characteristics. By creating Drosophila that express P3, and comparing them to flies that express A-Beta, using longevity assays and protein assays, we will assess the possible role of p3 in neurodegeneration and how it may interact with, and influence the neurotoxicity of A-Beta.

INVESTIGATION OF PROTEIN EXPRESSION PATTERNS OF THE EPIGENETIC GERMLINE REGULATOR MES-4 IN CAENORHABDITIS ELEGANSCarmen MaFaculty Mentor: Susan StromeThe oocyte provides the embryo with proteins that specify cell identity through epigenetic regulation. The mechanisms by which maternally provided epigenetic regulators specify cell identity are not well understood. In Caenorhabditis elegans (C. elegans), the maternally loaded epigenetic regulator Maternal Effect Sterile-4 (MES-4) is crucial for specification of germ identity and formation of a germline. Previous work in the Strome lab showed that MES-4 is required for ectopic expression of germline traits in some somatic cells of DRM mutant worms, suggesting that MES-4 may be expressed in and confer germline potential to some somatic tissues. To understand how MES-4 confers germline potential to somatic cells, it is important to determine which somatic cells express MES-4 during development. I live imaged transgenic worms that express MES-4 fused to Green Fluorescent Protein (GFP) (mes-4::gfp engineered into the endogenous locus) using confocal microscopy. My imaging showed that MES-4 is localized in germ cells at all stages and in some somatic cells at embryonic and early larval stages. Based on tissue maps, I speculate that the somatic cells that express MES-4 in larvae are seam cells, one of the few somatic cell types that undergoes stem-cell-like divisions during larval development. These findings suggest that MES-4 expression is not exclusive to the germline, but may instead be broadly linked to cells capable of stem-cell-like proliferation. Maternally provided MES-4 is critical for the primordial germ cells in embryos to form a functional germline, and embryonic expression is not sufficient for germline development. To gain insight into when MES-4 likely functions, it is important to analyze how long maternal MES-4 persists and when synthesis of new MES-4 from the zygotic genome starts. I performed genetic crosses to generate embryos that allowed me to distinguish embryo-expressed GFP-tagged MES-4 from untagged maternal MES-4, and live imaged these embyos and early larvae using confocal microscopy. I detected embryo-expressed MES-4::GFP in mid to late stage embryos. Determining where and when MES-4 is expressed will provide insight into how MES-4 functions to drive germline identity, which will enhance our understanding of how maternally provided factors and epigenetic regulators drive proper development.

LIBRARY OF GIANT PLANET REFLECTION SPECTRA FOR WFIRST AND FUTURE SPACE TELESCOPESAdam J SmithFaculty Mentor: Jonathan J FortneyFuture large space telescopes will be able to directly image exoplanets in optical light. The optical light of a resolved planet is due to stellar flux reflected by Rayleigh scattering or cloud scattering, with absorption features imprinted due to molecular bands in the planetary atmosphere. To aid in the design of such missions, and to better understand a wide range of giant planet atmospheres, we have built a library of model giant planet reflection spectra, for the purpose of determining effective methods of spectral analysis as well as for comparison with actual imaged objects. This library covers a wide range of parameters: objects are modeled at ten orbital distances between 0.5 AU and 5.0 AU, which ranges from planets too warm for water clouds, out to those that are true Jupiter analogs. These calculations include six metallicities between solar and 100x solar, with a variety of different cloud thickness parameters, and across all possible phase angles.

MAPPING EXCITATION-INHIBITION NETWORKS IN THE BARREL CORTEX OF MICE VIA MEASURING CHANGES IN CELLULAR ACTIVATION PROFILES AS A RESULT OF ACUTE STRESSSajita Caroni Shah-MoralesFaculty Mentor: Yi ZuoThe purpose of this project is threefold: 1) to determine how stress affects change in excitation-inhibition networks in the barrel cortex 2) to determine how somatostatin (SST+) inhibitory neurons fit into this pathway, and 3) to measure the behavioral defects caused by restraint stress. In order to determine how stress changes the excitation-inhibition network and what role SST+ inhibitory neurons play in this pathway, different levels of acute stress were induced via the Restraint Stress protocol and cellular activation profiles were measured via immunofluorescent assays. Furthermore, behavioral defects were quantified via the sucrose preference test. The expected results of this project are that SST+ inhibitory neurons inhibit NG+ excitatory neurons and pyramidal neurons in the barrel cortex directly rather than indirectly through inhibition of PV+ inhibitory neurons. It is also expected that rest after 7 days of stress will not be enough to observe a reversal of the stress effect at both the cellular level (cellular activation profiles) and the behavioral level (sucrose preference test).

MAPPING THE BRANCHPOINTS IN C. ELEGANSAmy Rose LeslieFaculty Mentor: Alan Mark ZahlerThe spliceosome is responsible for removing introns from the pre-mRNA. In spliced introns, there is an adenosine nucleotide bound to three other nucleotides, which forms the branchpoint. We are performing genetic and molecular experiments in the model organism C. elegans to understand how the spliceosome chooses the correct branchpoint. In this project, we will isolate and stabilize the branched lariat introns, and sequence them to identify the branchpoint. The lariats are rapidly degraded, making them nearly impossible to isolate. Full lariat degradation requires the debranching enzyme, DBR-1. We knocked out the dbr-1 gene from the worms in order to stabilize the lariats and learned that it is essential for viability. The auxin-inducible degron (AID) is a tag that allows for inducible degradation of tagged proteins by addition of auxin in the presence of the Arabidopsis TIR-1 gene. We successfully used CRISPRcas9 to tag the DBR-1 gene with the AID tag and can degrade the DBR-1 protein with auxin. After auxin addition, we hypothesize that any new splicing that occurs will lead to production of stable intron lariats. We will now isolate RNA from worms treated with auxin for 4 hours and look for the enrichment of lariat structured RNAs. If the lariats are successfully stabilized and isolated, we will then move forward with high throughput sequencing to identify branchpoints. Understanding the location of the branchpoints will provide new insights into the spliceosome's mechanism for choosing a specific splice site.

MASS GAIN IN NORTHERN ELEPHANT SEALS (MIROUNGA ANGUSTIROSTRIS): USING ENSO EVENTS AS A MODEL FOR LONG-TERM CLIMATE CHANGEZer BarokasFaculty Mentor: Theresa Rebecca KeatesClimate change is becoming an increasingly important topic of study, but its effects are still largely unknown. Oceanic ecosystems are vulnerable to such change because of the intricate and interconnected nature of oceanographic processes, and protecting them is especially important because of their high contribution to global productivity. Large predators are ideal sentinels for ocean health because many aquatic trophic cascades follow a bottom-up model, so predators with high energy needs are often the hardest-hit when productivity decreases.

I investigated how female northern elephant seals (Mirounga angustirostris) are affected by unusually warm ocean temperatures, using mass gain to measure foraging success, as a proxy for the ecosystems in which they feed. The seals were tracked across their post-molt migrations using satellite transmitter tags and weighed before their departure and after their return to the colony to calculate changes in mass. I used El Niño years as a way to simulate the forecasted warmer oceans of the future and predict the impact on their inhabitants by examining the effect of the El Niño-Southern Oscillation (ENSO) as measured by NOAA’s Oceanic Niño Index (ONI) on mass gained by the seals. I my analysis of the relationship between ONI and mass gain using linear regression showed no statistically significant relationship between ONI and foraging success, a result inconsistent with previous similar studies. Further research on El Niño’s effects on marine apex predators, as well as the mechanisms behind them, may provide a model for the fate of our oceans in a warming climate.

MECHANISTIC AND STRUCTURAL STUDIES ON HUMAN ASTROVIRUS SEROTYPE 8Carolina CuellarFaculty Mentor: Rebecca M DuboisThe human astrovirus is a primary cause of acute non-bacterial gastroenteritis in immunocompromised individuals, such as the elderly and infants. By the age of nine, an estimated 90% of children will have developed antibodies against the most common strain. Causing symptoms like vomiting, fever, diarrhea, and, more recently, meningitis, it is a relevant but poorly understood virus. The capsid of the virus contains globular proteins called spikes that are thought to be primarily responsible for attachment to the unknown host cell receptor. Although there are no vaccines or antiviral therapeutics to treat infection, current efforts in regards to viral treatment include identifying the unknown host cell receptor binding site and understanding the mechanism by which the spike infects human cells through identification and production of neutralizing monoclonal antibodies and studying their interaction with spike. Structural studies of HAstv spike and antibody binding are essential for identification of functional epitopes that are involved in receptor host cell attachment as well as possible therapeutic targets. The Human Astrovirus serotype 8 (HAstV8) spike was expressed and purified in order to perform mechanistic and structural studies with monoclonal antibody 2D9, which binds to a novel epitope not previously studied. Additionally, two engineered forms of the neutralizing antibody 2D9 were produced -- a humanized monoclonal antibody and a single chain variable fragment -- in order to increase the chance of crystallization. In conjunction to a solved structure of this complex, mechanistic studies done by a collaborator will allow for functional classification of epitopes and insights to viral biology. Future efforts will include binding studies of 2D9 with other strains in order to test for cross-reactivity for the purpose of vaccine design, and X-ray crystallography determination of the structure of 2D9-bound HAstV8 spike to understand binding epitopes and their functional role in neutralizing the virus. The goal of this project is to advance knowledge on the infective mechanism of a prevalent strain of the virus, HAstV8.

MICROBIOTA EFFECTS ON DIATOM SILICIFICATION AND GROWTHRodriel Alcayde BautistaFaculty Mentor: Marilou Sison-MangusSilica formation in diatoms is a key aspect in creating cell walls known as frustrules, a major structural component of the diatom cell. Diatoms typically grow in the company of marine bacteria coming several genera, some of which may affect the silicification process in the diatom host by, either inhibiting or facilitation diatom silica deposition. Biosilicification has been quantified by monitoring biosilica uptake to fluorescence rations in diatoms using the fluorescent dye commercially known as PDMPO 2-(4-pyridyl)-5-((4-(2-dimethylaminoethylaminocarbamoyl)methoxy)phenyl)oxazole] (McNair et al. 2015). This method helped quantify frustrule silica uptake and can be a useful tool to understand diatom growth under varying environmental conditions. In this study, we improve on past methods of quantifying silica uptake and growth in the diatom host under varying bacterial associations and assess silica uptaking using flow cytometry and microscopic analysis. The silica uptake of bacteria-free Thalassiosira, Sulfitobacter japonica treated Thalassiosira, and Pseudoalteromonas atlantica treated Thalassiosira was viewed using flow cytometry and microscopy to quantify PDMPO intensity, cell size, and enumerate live diatom cells stained with and without PDMPO. We hypothesize that in varying bacterial conditions, beneficial diatom microbiota will allow diatoms to grow more quickly, therefore binding more silica and PDMPO dye into their frustrules.

MONITORING ACTIVITY LEVELS IN A DROSOPHILA MODEL OF ALZHEIMER'S DISEASE WITH KNOCKDOWN OF THE SLEEP-REGULATING INSOMNIAC PROTEINJacob Samuel Bornstein, Hana Pak Chuang, Manolo Adrian MejiaFaculty Mentor: Jeremy LeeAlzheimer’s disease (AD) is a neurodegenerative disease characterized by a shortened lifespan; cognitive impairment, memory loss, decreased motor abilities, and an accumulation of Amyloid Beta (A?) plaques in the brain. Studies suggest that sleep deprivation may accelerate AD pathology by interfering with the clearance of neurotoxic forms of A? (Spira, et al., 2013). Little is known about the functional need for sleep or its effect on AD pathology. Clinical studies show a correlation between poor sleep quality and AD progression. Our project studies the effects of sleep deprivation on the progression of AD-like pathology in Drosophila. Drosophila exhibit AD-like pathology when a transgene encoding human A?42 is expressed in the neurons of their central nervous system; we utilize these as our AD model flies.

We developed a Drosophila model to study the relationship between AD pathology and sleep deprivation. Expressing a transgene encoding RNA which targets the Drosophila protein Insomniac for knockdown, induces sleep deprivation. Our lab has shown that AD model flies with Insomniac knockdown have a shorter mean lifespan than AD model flies that express A?42. Insomniac knockdown alone did not show a decreased lifespan. We are monitoring the sleep-wake cycles and horizontal locomotion of Insomniac knockdown AD model flies using a Drosophila Activity Monitor (D.A.M.) and comparing them to AD model flies. This will allow us to confirm that Insomniac knockdown induces sleep deprivation and to evaluate whether sleep deprivation accelerates the behavioral defects associated with the AD-like pathology in our AD model flies.

NORTHERN ELEPHANT SEAL DIVE DEPTH AS A RESULT OF EL NIñO EVENTSJulieta Berenice GomezFaculty Mentor: Patrick William RobinsonAs temperatures have been increasing yearly due to human activity, it is important to see how the changing climate, specifically El Niño, will affect marine mammals. El Niño causes warming of sea surface temperatures (Rampage 1986). During El Niño years, warm southern currents replace cool, nutrient-rich water with warm nutrient-poor water. The dive depth of sixty adult female Northern elephant seals (Mirounga angustirostris) relative to sea surface temperature was monitored over a six-year period (2010-2015). Ten adult female Northern elephant seals were sampled every year for six years. This study will compare changes in northern elephant seal dive depth relative to sea surface temperature during El Niño and non-El Niño years. It is expected that Northern elephant seals will dive deeper during El Niño years because of warmer water temperatures. However, no significant correlation between dive depth and sea surface temperature was found.

OBOC CYCLIC PEPTIDE LIBRARY TARGETING E2FAlexandra Chloe TurmonFaculty Mentor: Scott LokeyCancer develops due to dysregulation of the cell cycle. In mammalian cells, cell growth and division are in part mediated by an interaction between the proteins E2F, a transcription factor, and Rb, retinoblastoma protein. Rb modulates the cell cycle by binding to E2F, inhibiting transcription and cell growth. Dysregulation of this interaction is responsible for several cancers, such as retinoblastoma cancer. We will be targeting this E2F/Rb interaction by designing an Rb mimicking cyclic peptide that would inhibit the E2F protein in cancers. The Lokey Research Group focuses on cyclic peptides due to their unique cell permeability properties. Cyclic peptides can bury their side chains and change conformation to increase cell permeability, allowing for the incorporation of unnatural and charged amino acids to their sequence. We will use “One-Bead-One-Compound” solid phase synthesis to make our E2F-targeting cyclic peptides; they will be synthesized on an HMBA solid support resin bead. This allows us to generate a large library of compounds with a unique sequence on each resin bead. An OBOC compound library allows for maximal sequence variation during synthesis, and then to be sequenced and screened in various assays. We designed our OBOC library to incorporate amino acids that we determined via virtual modeling to have interacting potential with the E2F active site. Once synthesized each cyclic peptide will be sequenced on an Orbitrap and tested for its permeability. Hits that show good cell permeability will be resynthesized on a larger scale and put through follow-up bioactivity studies.

OUTBREAKS OF THE PURPLE SEA URCHIN ARE DEFORESTING REEFS IN SOUTHERN MONTEREY BAY, CATorrey Raquel GorraFaculty Mentor: Mark H CarrSince 2014, kelp abundance has rapidly declined around Southern Monterey Bay, California. One possible explanation for the sudden loss of kelp forests is the outbreak in populations of voracious sea urchin grazers. When urchin populations are uncontrolled, they overgraze kelp forests, thereby shifting forested habitats to an alternative “barren” state. To evaluate whether the observed kelp declines around Monterey Bay might be attributed to increased sea urchin grazing, we conducted subtidal surveys to estimate the extent of barrens and forests around the region (i.e., current ecosystem state), and to evaluate sea urchin density and biomass at depths of observed kelp loss. We also evaluated urchin condition (i.e., gonad index) in three ecosystem states (kelp forests, barrens, and at urchin foraging fronts) as a measure of their condition. Purple urchins (S. purpuratus) and not red urchins (S. franciscanus) were found to have the largest densities within barrens, leading to the possible conclusion that S. purpuratus exerts a stronger influence on state shifts (p=0.001). The lower gonad index of S. purpuratus in barrens likely reflects heightened hunger demands and starvation, leading to their increased foraging activity and exposure (p =0.003; p<0.0001). Moreover, because only S. purpuratus comprise fronts, this suggests that they are fundamentally contributing to kelp deforestation.

PRP-8 ALLELES SUPPRESS CRYPTIC SPLICING IN C. ELEGANSAndrea RamirezFaculty Mentor: Alan Mark ZahlerSplicing is an important mechanism that allows for regulation of gene expression. The spliceosome is a key player in this process since it functions to remove noncoding regions called introns and ligate protein coding regions called exons. Splice sites determine where the spliceosome will cut and are characterized by consensus sequences at the 5’ splice site, 3’ splice site, and branchpoint of an intron. In cases where splice sites are mutated, as in several human diseases, cryptic splice sites can be activated leading to varying gene products.

Although we do not fully understand why cryptic splice sites are used, we can use genetic tools to help us find pieces of the puzzle. We ran a genetic screen in C. elegans to find alleles of the spliceosome component prp-8 in hopes of finding suppressors of cryptic splicing. One of the alleles we found is located in the “740 loop” region of the spliceosome, which interacts with U5&U6 snRNA. This allele was able to suppress the use of cryptic splice sites in C. elegans. A closer look at this allele helped us gain insight on how the spliceosome chooses to cut at these sites.