Student Profiles Archive - Beckman Scholars
Here you will find information about past and present students funded through scholarships administered by the Undergraduate Research Center - Sciences. We are proud of the achievements of our research scholars.
Please click on the program year to get information about the supported students, their mentors and their research projects.
| Andrew Nguyen
Mentor: Dr. Hanna K.A. Mikkola
Title: Defining MLLT3 regulated molecular pathways in hematopoietic stem cell self-renewal
Andrew Nguyen is a third year majoring in Molecular, Cell, and Developmental Biology and minoring in Biomedical Research. He has been conducting research in the laboratory of Dr. Hanna Mikkola since his freshman year. Andrew is currently investigating the role of mixed-lineage leukemia translocated to 3 (MLLT3) as an upstream transcriptional regulator of hematopoietic stem cell self-renewal.
Hematopoietic stem cells (HSCs) are multipotent blood cells that can self-renew and differentiate into all blood cell types. These two properties allow HSCs to rapidly expand and reconstitute the entire hematopoietic system when transplanted into an irradiated recipient. As such, HSC transplantation has been used to cure congenital and acquired hematopoietic diseases.
However, limitations in HLA-matched bone marrow donors create a need for new methods to generate and maintain HSCs in vitro. To this end, pluripotent stem cells (PSC), including human embryonic stem cells (hESC) and induced pluripotent stem cells (iPSC), are potential unlimited sources of HSCs that can bypass the problem of HLA-matching and graft versus host disease. However, differentiation efforts on PSCs have led to ineffective HSC that cannot self-renew and cannot engraft.
To derive clinically useful HSCs, we must understand the molecular pathways that give rise to self-renewing HSCs, but are not established in PSC-derived hematopoietic cells. After comparing the gene expression patterns of enriched HSC's, we saw that MLLT3 is highly upregulated in self-renewing HSCs of the fetal liver while downregulated in PSC-derived hematopoietic progenitors. Interestingly, MLLT3 fuses with MLL in acute myeloid leukemia, which causes an aberrant expression of downstream gene targets and uncontrolled growth of hematopoietic cells. To this end, Andrew will explore the mechanisms of wild type MLLT3 as a regulator of the global transcriptome. The characterization of the genetic network behind HSC self-renewal will provide insight into the molecular signals and cues that may be utilized to improve the expansion of HSC's in culture for therapeutic purposes.
After graduating, Andrew plans to pursue an MD/PhD program. He would like to thank Dr. Mikkola, postdoctoral mentor Dr. Vincenzo Calvanese, the entire Mikkola lab, advisor Dr. Ira Clark, and Dr. Tama Hasson for their expert guidance and support. He would also like to thank the Arnold and Mabel Beckman Foundation for their generous support and for this invaluable research opportunity.
| Mr. Stephen Chiu
Mr. Shephan Chiu
Mentor: Dr. Benhur Lee
Title: Characterization of Novel Nipah Virus Matrix Protein Mutants
Stephan Chiu is a 4th year Microbiology, Immunology and Molecular Genetics Major with a Biomedical Research Minor. Since Summer 2010, he has been conducting research in Dr. Benhur Lee's Lab, studying Nipah Virus, a recently emerging and largely uncharacterized paramyxovirus.
Nipah virus (NiV) is a lethal emerging zoonotic virus of the Paramyxoviridae family, resulting in its classification as a Biosafety Level 4 pathogen, the highest level of biosafety containment. The Nipah Matrix (M) protein is essential for the assembly of viral components and subsequent budding from host cells. Similar to several other paramyxoviral M proteins, NiV-M is also capable of independently budding in the absence of other viral components, forming virus-like particles. Previous studies have shown that mutations in critical sites in NiV-M can result in loss of budding function. In this study, fifteen new sites in the Matrix protein that are highly conserved across several genera of the Paramyxoviridae family were identified using computer alignment analysis. Using site-directed mutagenesis, these sites were independently mutated in order to assay their importance for NiV-M budding. Upon transfection into 293T cells, most NiV-M mutants displayed a moderate to severe degree of budding deficiency. In addition, visualization of NiV-M within transfected cells using fluorescence microscopy revealed distinct mutant phenotypes, including nuclear retention and loss of characteristic punctate appearance. Further investigation of these NiV-M mutants in the context of other paramyxoviral Matrix proteins may reveal conserved or distinct features in NiV budding that will facilitate development of novel therapeutic strategies.
| Ms. Jessica Ong
Ms. Jessica Ong
Mentor: Dr. Karen Lyons
Title: The Role of the Protein CCN2 in the Development of the Nucleus Pulposus of the Intervertebral Disc
Jessica Ong is a third year Molecular, Cell, and Developmental Biology major and Departmental Scholar, also minoring also in Biomedical Research. She conducts research in Dr. Karen Lyons' laboratory studying the protein CCN2/Connective Tissue Growth Factor (CTGF).
CCN2 is secreted into the extracellular matrix (ECM) where its serves as a matricellular protein--one that does not contribute to the ECM structure. However, its exact function remains elusive but it is known to be vital for cellular adhesion, migration, and ECM production. It is expressed in a variety of organ systems, including the skeletal system, where we are investigating its role within the nucleus pulposus (NP) of the intervertebral disc (IVD). At the center of the IVD, the NP exists as a gelatinous structure that acts as a shock absorber for the spine, where intact ECM composition is imperative to its function. ECM degradation in the NP has been proposed to initiate IVD degeneration, a major cause of lower back pain. We have hypothesized that
CCN2 is involved in the development and maintenance of the NP. Our examination of a CCN2 enhanced green fluorescent protein mouse line has illustrated CCN2 expression within the notochord, the NP precursor, and within the NP and supporting structures throughout adult life. We have also utilized a cartilage specific depletion of CCN2 to examine its role in NP development, ablating its functional gene from the notochord. These mice exhibit overall defects in vertebral column formation, including widened and distorted NP. Immunostaining of major proteoglycans expressed in the NP revealed improper ECM deposition and remodeling. Overall, these results have demonstrated that CCN2 is integral to proper ECM remodeling in the NP.
Jessica is pursuing a career as a translational researcher. She appreciates the generous support from the Beckman Scholars Program in facilitating her future. Furthermore, she would like to thank Dr. Karen Lyons, Faith Hall-Glenn, and Dr. Tama Hasson for their guidance and training.
| Mr. James Chen
Mr. James Chen
Mentor: Dr. Hong Wu
Funding: Beckman Scholar
Title: Role of Bmi-1 in Leukemic Stem Cell Self-Renewal Following Pten Deletion
James Chen is a fourth year Microbiology, Immunology, and Molecular Genetics major studying under the direction of Dr. Hong Wu and Dr. Wei Guo in the Department of Molecular and Medical Pharmacology at UCLA. Dr. Wu's laboratory has generated a leukemia mouse model in which Pten, a tumor suppressor gene, is deleted in the hematopoetic stem cell compartment. In this model, Pten deletion has been linked to stem cell exhaustion; however, strikingly despite this, they have identified a rare population of leukemic stem cells (LSC). For his project, James is studying the role of Bmi-1 in LSC self-renewal. Bmi-1, a proto-oncogene within the Polycomb Group family of proteins, has been implicated in self-renewal. Other groups have shown that c-Myc regulates Bmi-1 expression at the transcriptional level. In Dr. Wu's model, c-myc is over-expressed as a result of an aberrant chromosomal translocation with TCR alpha/delta. After assessing whether Bmi-1 is disregulated in LSCs, he will perform RNAi and transplantation studies to determine Bmi-1's role in LSC self-renewal in vivo.
James is studying for an MD/PhD (MSTP) and a career in biomedical research. He is thankful to Dr. Hong Wu as well as the Beckman Foundation for providing him with this remarkable research opportunity.
| Mr. Bac Nguyenn
Mr. Bac Nguyen
Mentor: Dr. David Krantz
Title: Studying learning and memory through the characterization of a novel neurotransmitter transporter mutant in Drosophila
Bac Nguyen is a fourth year Microbiology, Immunology and Molecular Genetics major conducting research in Dr. David Krantz's Neuroscience and Psychiatry Lab. In this lab, which studies neurotransmitter transporters, Bac works directly with graduate student Lisa Brooks under the mentorship of Dr. David Krantz. Lisa Brooks' project is to characterize a novel neurotransmitter transporter, “DVX”, expressed in the Drosophila mushroom bodies. Since neurotransmitter transporters are required for synaptic transmission and the mushroom bodies are important for learning and memory, we hypothesize that the DVX mutants may have a defect in learning and/or memory. Bac's primary project is to adapt and apply a courtship-conditioning assay to the DVX mutants in order to quantify potential differences in learning and memory. In addition, Bac has been using Drosophila to model Parkinson's disease, focusing on the neurotoxic effects of pesticides. Bac hopes to pursue a career in academic medicine in the future, in which he will practice medicine, train residents and perform research.
Bac would like to personally thank Lisa Brooks and Dr. David Krantz for their help and guidance, and the Beckman Foundation for providing the opportunity to pursue this work and explore research at a level he could not have imagined.
| Ms. Paowen Wong
Ms. Paowen Wong
Mentor: Dr. Richard Kaner
Title: A Simple Process to Synthesize Poly (3-hexylthiophene) Nanofibers Using Initiator-assisted Polymerization
Paowen Wong is a Departmental scholar who will complete both of her Master degree in Chemistry and her Bachelor degree in Chemistry-Materials Science in Summer 2010. Since Fall 2008, Wong has worked on the synthesis of poly-3-hexylthiophene (P3HT) nanofibers, an organic semiconductor material which is used in solar cells and field-effect transistor applications.
The synthesis of P3HT nanofibers was investigated via initiator-assisted polymerization. The addition of a chemical initiator during polymerization of P3HT accelerates the kinetics of this reaction, and has been reported to function as a catalyst in the mechanism leading to nanofibers of polythiophene – the parent compound of P3HT. Purification protocols of the final product were studied along with synthetic variables such as temperature, solvent, and length of polymerization time. Transparent conductive thin films of in-house produced P3HT nanofibers were deposited on glass substrates for characterization purposes.
The nanoscale morphology of the polymer was investigated using a scanning electron microscope; it was observed that the aspect ratio of produced nanofibers is controlled by the tailoring of the synthetic reaction conditions. Future goals include the fabrication of field effect transistors using P3HT as the semiconductor active layer; also, the generalization of the herein described procedures will be attempted to target other semi-rigid conducting polymers such as polythiophene derivatives poly (3-alkylthiophene) and poly (3-alkoxythiophene).
Wong sincerely appreciates the support from the Beckman Research Scholarship which provides her with the opportunity to work as an independent researcher at the University of California, Los Angeles from Summer 2009 to Summer 2010. Here, Wong would like to thank Dr. Hasson, Dr. Crosbie and Mr. Flaxman for their assistance. Furthermore, Wong would like to express her gratitude toward Prof. Ric Kaner, Julio D'Arcy, and everyone in the Kaner lab for their continued support.
| Ms. Karen Aanensen
Ms. Karen Aanensen
Mentor: Dr. Benhur Lee
Title: Exploring Differing Determinants of Virulence between the Malaysian and Bangladeshi Nipah Viral Envelope Proteins
Karen Aanensen is a fourth year student, pursuing a degree in Microbiology, Immunology and Molecular Genetic. She conducts research in Dr. Benhur Lee's lab studying Nipah Virus (NiV). There are two strains of Nipah virus, the Malaysian and Bangladeshi strain, with human mortality rates around 40 percent and 70 percent respectively. During the terminal stage of this infection, severe brain stem dysfunction is observed.
Ms. Aanensen is investigating amino acid differences which may contribute to the differing human mortality rates. Specifically, she is comparing the two strain's amino acid sequences of the attachment protein (NiV-G). NiV-G uses either ephrin-B2 (B2) or ephrin-B3 (B3) as host-cell entry receptors. B3 but not B2 is found in the brain stem. Therefore, any residue differences that increase NiV's binding affinity to B3 may increase the host-cell entry efficiency within the brain stem. This may consequently contribute to a more severe brain stem infection, brain stem failure, and a higher mortality rate. Our hypothesis is that certain residues on the Bangladeshi strain of NiV-G result in an increased binding affinity to B3 when compared to the Malaysian strain.
Ms. Aanensen has introduced the Bangladeshi amino acid differences onto the Malaysian strain of NiV-G. She then compared the B2 and B3 binding affinities of the parental strain and mutant strains. This was achieved by expressing the constructs in Chinese Hamster Ovarian cells (which lack B2 and B3 receptors) and developing binding curves of B2 or B3. Preliminary studies suggest that one of the NiV-G mutants may increase the binding affinity to B3. Also, she will be testing mutants in which multiple amino acid residues have been introduced in order to assess if certain residue differences act synergistically. Infections will be carried out using pseudo-typed VSVG virus in order to see if these mutants influence viral infectivity. Finally, she will be investigating differences on the other envelope protein, the fusion protein, which is essential for viral fusion into the host cell.
| Ms. Pwint Khine
Ms. Pwint Khine
Mentor: Dr. Richard Kaner
Title: Synthesis of Polythiophene and Poly(3,4-ethylenedioxythiophene) Nanofibers for Thin Film Deposition
Pwint Khine is a fourth year student, pursuing a degree in Biochemistry. Since Fall 2009, she has been working on the synthesis and fabrication of one-dimensional polythiophene (PT) and poly(3,4-ethylenedioxythiophene) (PEDOT) nanofibrillar thin films.
One-dimensional (1-D) nanostructures of PT and PEDOT are the focus of intensive research due to their enormous potential towards applications in electronic devices and light-emitting diodes. A vast number of techniques exist for shaping of PT and PEDOT into nanostructures; however, they all suffer from limitations such as amorphous and a random orientated polymer chains. On the other hand, our initiator-assisted polymerization successfully synthesizes bulk quantities of nanofibers by the introduction of additives that lead to a network of interconnected 1-D nanostructures. The purpose of this study is to synthesize conductive PT and PEDOT nanofibers using initiator-assisted polymerization under different synthetic conditions in order to produce free-standing thin films. To produce a thin, uniform, and transparent film, deposition of nanofibers on a variety of substrates has been developed. A monolayer of nanofibers, present at the interface between water and oil, is engineered to coat a solid surface using an interfacial surface tension gradient. A film grows in seconds and dries in minutes at ambient conditions, this transparent coating is collected on substrates such as glass, ITO, and mica. Characterization of a thin film is carried out via scanning electron microscopy to study morphology, ultraviolet-visible light spectroscopy to investigate chemical structure, and cyclic voltammetry to analyze redox behavior. Our results show a high yield of PT and PEDOT nanofibers, thin film deposition at the water-oil interface, and a novel technology for fabricating freestanding films. Future goals include process scale-up, measurement of electrical properties such as sheet resistance, and device fabrication.
Pwint greatly appreciates the vision and funding from the Beckman Research Scholarship. Here, Pwint would like to express gratitude toward Prof. Ric Kaner and Julio M. D'Arcy for their guidance, encouragement, and Dr. Hasson and Dr. Crosbie for assistance.
| Mr. Jaspreet Sandhu
Mr. Jaspreet Sandhu
Mentor: Dr. Kent Hill
Title: Identification of Genes Regulating Social Behavior in T. brucei
Jaspreet Sandhu is a fourth year student, majoring in Microbiology, Immunology, and Molecular Genetics. He conducts his research in Dr. Kent Hill's laboratory that studies Trypanosoma brucei, the causative agent of African Sleeping Sickness.
Recent advances in Dr. Hill's laboratory have shown that inoculating insect-stage T. brucei cells upon semisolid agarose surfaces induces social behavior. This behavior is defined by the formation and migration of macroscopic communities, and the ability for each community to sense and avoid opposing communities. Social behavior in T. brucei provides a system for studying environmental sensing, host-pathogen interactions, and cell-cell communication.
Jaspreet's project seeks to identify genes that regulate the social behavior of T. brucei. He is taking two approaches. First, he is working on a forward genetic screen using a tetracycline-inducible RNAi library of T. brucei cells to identify knockdown mutants that exhibit aberrant social behavior. He is currently in the process of phenotyping clonal populations that have been isolated by flow cytometry. In addition, he is applying a targeted approach to investigate the potential role of classical secondary messenger pathways. To do this, he is performing functional studies on a number of candidate genes that may serve as downstream effectors in these pathways.
Jaspreet will be pursuing a career in academic medicine, in which he will practice alongside his research. He would like to thank Dr. Kent Hill and the Beckman Scholars Program for providing him with an excellent foundation for his future career. In addition, Jaspreet would like to thank HoangKim Nguyen, Dr. Tama Hasson, and the members of the Hill laboratory for their continued support and guidance.
| Mr. Ryan Young
Mr. Ryan Young
Mentor: Dr. Benjamin J. Schwartz
Title: Solvation Dynamics of Alkali Metal Anions in Various Solvents and Their Effects of Charge-Transfer Reactions
Ryan Young is a fourth year studying Physical Chemistry under the guidance of Dr. Benjamin J. Schwartz in the Department of Chemistry and Biochemistry. Ryan's research examines how the motions of solvent molecules influence the rates of electron transfer reactions, which are fundamental to chemistry and biology. When a solvated alkali metal anion is excited with a laser pulse the surrounding solvent molecules interact with the excited-state wave function, forcing the ejection of the excess electron into the solvent. This can then be detected by a different laser pulse at a different wavelength. Due to the simplicity of the atomic solutes, any change in signal is directly related to the motions and interactions of the solvent molecules with the solute. Different solvents will of course yield different dynamics, as will changes to the local environment, such as variations in the temperature. The focus of Ryan's research is the comparison of the different dynamics induced by photoexcitation of anions of different alkali metals using ultrafast pump-probe spectroscopy. From these comparisons a better understanding of the degree of control solvation dynamics can have on chemical kinetics can be made, and a major theoretical device of non-equilibrium statistical mechanics can be tested. He plans on pursuing the study of chemical dynamics with the ultimate goal of becoming a professor at a research university.
| Ms. Jenny Yawei Yang
Ms. Jenny Yawei Yang
Mentor: Dr. Stephen Cederbaum
Title: Small Interference RNA for the arginine and polyamine metabolism with the use of a tetracycline-inducible vector based siRNA system
Jenny is a third year Honors Molecular Cell and Developmental Biology major and a Neuroscience minor conducting research under the mentorship of Dr. Stephen Cederbaum in NPI at the David Geffen School of Medicine. Jenny is currently making Short Interfering RNAs (siRNAs) which allow for the specific silencing of a target gene by inhibiting translation and inducing targeted RNA degradation within a cell. Preliminary comparative studies done last year on primary neuronal stem cells isolated from both wildtype and arginase I knockout mice have suggested that (1) a loss of arginase I expression affects both proliferation and differentiation of neuronal stem cells in culture and (2) that these arginase I null stem cells actually exhibit an increase in proliferation and differentiation when cultured under appropriate conditions. siRNA constructs for several genes that play a role in arginine metabolism, including Arginase I (AI), Ornithine Aminotransferase (OAT), Agmatinase (AGM), and Ornithine Decarboxylase (ODC) are currently being made and verification of the ability of each siRNA to abrogate the targeted genes have been done with both RT-PCR and fluorescent microscopy to reveal a decrease in gene expression. siRNAs for each gene will be cloned into a vector containing a tetracycline-responsive derivative of the human U6 promoter, pU6tet01.6, to allow for the conditional expression of these siRNAs. The effects that siRNA perturbation of the various genes has on proliferation and differentiation can then be studied in two cell lines that are suitable models for neuronal stem cells, specifically SH-SY5Y, a human neuroblastoma cell line, and NTera2/D1, a human embryonal carcinoma cell line. Upon graduation, Jenny plans on pursuing a joint MD/PhD in order to become a research physician specializing in the field of neurobiology, and she hopes to make strides in the fight against neurodegenerative diseases. Aside from research, Jenny also loves art, photography, and tap dances during her free time.
| Mr. Bryan Harada
Mr. Bryan Harada
Mentor: Dr. James Bowie
Funding: Beckman Scholar
Title: Structure and Function of the SAM Domain of Diacylglycerol Kinase δ
Bryan is a third-year biochemistry major, mathematics minor researching under the direction of Dr. James Bowie in the Department of Chemistry and Biochemistry. For his project, Bryan is studying the structure and function of diacylglycerol kinase δ (DGKδ). DGKδ is a member of a family of kinases which convert diacylglycerol to phosphatidic acid. Since both diacylglycerol and phosphatidic acid are important lipid second messengers, the DGK isozymes may play an important role in regulating the signaling pathways which involve these two molecules. DGKδ possesses a sterile alpha motif (SAM) domain, which is a conserved structural motif found in a variety of proteins. Most SAM domains mediate protein-protein interactions, and the SAM domain of DGKδ has been shown to mediate the homo-oligomerization of DGKδ. This oligomerization is thought to be involved in determining the intracellular localization of DGKδ. In order to study the role of this oligomerization, Bryan has developed a novel in vivo fusion-reporter screen to identify monomeric mutants of the SAM domain of DGKδ. Identification of these monomeric mutants will reveal which amino acid residues are critical for oligomer formation as well as provide mutant proteins for further biochemical, biophysical, and structural characterization. Ultimately, Bryan aims to map the oligomeric interface of the DGKδ and solve the structure of the SAM domain of DGKδ, so that he can use this structural information to study the function of DGKδ oligomerization in vivo. This information may give insight into the regulation of DGKδ's activity and its role in intercellular signaling. After graduating from UCLA, Bryan plans to attend graduate school and pursue a Ph.D. in biochemistry or biophysics.
| Mr. Omid Kohannim
Mr. Omid Kohannim
Mentor: Dr. Aldons J. Lusis
Funding: Beckman Scholar
Title: Discovering Potential Candidate Genes for Hypercholesterolemia in Mouse Models
Omid Kohannim is a fourth-year Honors Microbiology, Immunology and Molecular Genetics major, Mathematics minor student pursuing a research project under the mentorship of Dr. Aldons J. Lusis in the Depatment of Medicine at UCLA. Omid is investigating the genetic components of hypercholesterolemia, a major risk factor of atherosclerosis, in mouse models. This positional cloning project began when a Quantitative Trait Locus (QTL) was identified in mouse chromosome 15, correlating with differences in blood cholesterol between two particular strains of mice: Balb/cJ and MRL/mpJ. These two strains of mice were then bred for many generations in a selective way in order for potential candidate genes to be identified. Omid compared the nucleotide sequence and mRNA expression levels of these genes between the two strains, and found Zhx2, a known zinc-finger transcription factor, to be differentially expressed. This suggested that Zhx2 is regulating a gene that plays a role in biochemical pathways relevant to cholesterol. Currently, siRNA, microarray and transgenic experiments are being conducted to confirm this proposed function of Zhx2 both in mice and human cells. Omid plans to pursue medical practice and research in the future. He is thankful to Dr. Aldons J. Lusis as well as the Beckman Foundation for providing him with this research opportunity.
| Ms. Alissa Minkovsky
Ms. Alissa Minkovsky
Mentor: Dr. Christopher Denny
Funding: Beckman Scholar
Title: Establishing stable expression of EWS/FLI1 in primary cell lines in the search to find a Ewing's Sarcoma cell of origin
Ewing's sarcoma is a poorly lethal pediatric cancer characterized by a chromosomal translocation that results in the juxtaposition of the EWS gene on chromosome 22 with one of five different ETS family transcription factors of chromosome 11, the most common of which is the Fli1 gene. Alissa Minkovsky, a Junior Microbiology, Immunology, and Molecular Genetics Major, is studying this EWS/Fli1 chimeric gene in the lab of Dr. Christopher Denny her first year here at UCLA. She is working, with the guidance of Gary Potikyan, towards attaining stable expression of the EWS/Fli1 protein in murine embryonic stem cells by altering tumor suppression pathways in order to come closer to finding the cell of origin in EFTs. Stable expression of EWS/Fli1 has been achieved in NIH3T3 murine cell lines which already possess numerous mutations in tumor suppression pathway genes but expression has been toxic to most primary cell lines. Strong evidence exists that alteration of the INK4a/ARF network, is necessary for oncogenesis in Ewing's. The knockdown of p16, a protein that is upstream in the p53 and RB tumor suppressor pathways, will hopefully make expression of EWS/Fli1 stable in mouse embryonic cells so that the cell types that do tolerate expression of EWS/Fli1 when the ES cells are differentiated in an tetracycline-inducible system can be identified. Alissa is studying towards a MD/PhD and a career in biomedical research.
| Christina Jayson
Mentor: Dr. Carla Koehler
Title: Generating a Zebrafish Model of Deafness-Dystonia Syndrome Using Transcription Activator-Like Effector Nuclease (TALEN) Technology
Christina Jayson is a fourth-year pursuing a Biochemistry major and Spanish minor. She joined the Koehler lab of the Biochemistry department in the fall of her second year. Under the guidance of her principle investigator, Dr. Carla Koehler, and with previous mentorship from her post-doctoral mentor, Meghan Johnson, she is characterizing mutations in mitochondrial assembly in the vertebrate model zebrafish.
Defects in mitochondrial biogenesis result in inherited mitochondrial diseases that are typically referred to as mitochondrial myopathies and neuropathies. Mutations in components of the mitochondrial protein import pathway, TIMM8A and TIMM8B, can lead to Mohr-Tranebjaerg Syndrome or Deafness Dystonia Syndrome. This disease is caused by defective mitochondrial import and is characterized by progressive sensorineural hearing loss, dystonia, mental deficiency and visual disability. Previous research by Dr. Koehler et al. indicates the disease results from a mutation in Deafness Dystonia Protein1 (DDP1) that affects mitochondrial protein import. Christina is generating a zebrafish line with germline mutations in TIMM8A and TIMM8B to phenotypically characterize the effects of this disease on a vertebrate model. In tandem to these studies, she will investigate the role of mitochondrial trafficking in neuronal development and axonal branching in primary motor neurons to understand how damage affects the mitochondrial network in development. Using zebrafish to recapitulate the resulting disease phenotypes from targeted protein mutation will allow her to generate a model organism that has more clinical and chemical relevance for studying mitochondrial protein translocation and the degenerative consequences that arise when the import system is compromised.
Christina greatly appreciates the support of the Arnold and Mabel Beckman Foundation. She would like to thank Dr. Carla Koehler, Dr. Tama Hasson and the members of the Koehler lab for their guidance, and for the opportunity to conduct undergraduate research.
| Andrew Lin
Project Title: Functional Characterization of Novel Microneme and Rhoptry Transporter Proteins inToxoplasma gondii
Andrew Lin is a fourth-year majoring in Microbiology, Immunology, and Molecular Genetics and minoring in Biomedical Research. He began as an undergraduate researcher with Dr. Bradley in the winter quarter of his freshman year. The Bradley lab studies the host-pathogen interactions of the apicomplexan parasite, Toxoplasma gondii. Andrew’s research focuses on novel proteins that localize to the microneme and rhoptry, two compartments involved in essential T. gondii invasion processes.
The Apicomplexa are a phylum of parasitic protozoa that includes Plasmodium falciparum, a parasite responsible for malaria, and Toxoplasma gondii, a widespread pathogen considered to be the leading cause of death attributed to foodborne illness. These parasites use a sophisticated strategy for infection, involving active invasion of their host cell, creation of a protective niche, and finally egress from the host cell. Effective apicomplexan invasion requires the polarized secretion of proteins from the micronemes, which are responsible for parasite attachment to the host cell. This is followed by secretion of proteins from the rhoptry, whose proteins are involved in both the hijacking of cellular machinery and the formation of a moving junction structure by which the parasite is able to pull itself into the host cell. While much is known about these released constituents of the microneme and rhoptry, very little is known about the transporter proteins in the delimiting membranes of these organelles. By studying these novel transporters, Andrew hopes to gain insight into the uncharacterized resident proteins of the microneme and rhoptry with the goal of ultimately contributing to the development of better therapies for these deadly parasites.
Andrew would like to thank Dr. Peter Bradley, all the members of the Bradley lab, and the URC-Sciences office for their assistance and guidance through his research, as well as for creating a great environment to develop as a scientist. Additionally, he would like to thank the Arnold and Mabel Beckman Foundation for their generous support and this invaluable research opportunity.
| Mr. Shivam Zaver
Mr. Shivam Zaver
Mentor: Dr. Genhong Cheng
Title: Examination of Novel Signaling Programs in Innate Antiviral Immunity
Shivam Zaver is a third year Biochemistry major. He has been working in the lab of Dr. Genhong Cheng since early 2012. Under the guidance of Dr. Cheng and Dr. Kislay Parvatiyar, he has been researching the role of novel proteins involved in the innate antiviral signaling pathway. After graduating, Shivam hopes to attend a Medical Scientist Training Program.
The innate arm of the immune system provides the first line of defense against invading pathogens. In the context of innate antiviral immunity, the induction of type I interferons (IFNα, IFNβ), key cytokines secreted during the course of virus infection, is critical in limiting viral replication and spread. Activation of type I interferons (IFN) is regulated by several transcription factors including Interferon Regulatory Factor 3 (IRF3) which undergoes C-terminal phosphorylation by the Tank Binding Kinase 1/ IκB Kinase I kinases (TBK1/IKKi), which promotes IRF3 trans-activation, allowing for IFN production. The mechanisms by which the TBK1/IKKi kinases are activated to signal to IRF3 are not really well understood. In an effort to identify upstream kinases for TBK1 activation, an unbiased screen utilizing a collection of 564 kinases provided by OriGene was performed. Twenty TBK1 activating kinases identified from the screen were then further validated to confirm activation of a TBK1 phosphorylation dependent transcription factor. The requirement for these kinases by TBK1 in supporting IRF3 activation will be investigated. In vitro kinase assays using screened kinases (TBK1 substrates) will be performed and phospho-acceptor sites will be identified to determine the physiological role of TBK1 phosphorylation. Aberrant activation of TBK1 has been demonstrated in oncogenic KRAS dependent tumors. Thus, identification and targeting of key TBK1 activating kinases could potentially provide a therapeutic target to combat select tumors.
Shivam greatly appreciates the support of the Beckman Research Scholarship, and would also like to thank Dr. Genhong Cheng, Dr. Kislay Parvatiyar, Dr. Tama Hasson, and the members of the Cheng laboratory for their continued support and guidance.
| Mr. Alexander Yeh
Mentor: Prof. K. N. Houk
Title: Theoretical Investigations towards the Synthesis of Tamiflu
Alex Yeh is a fourth year Physical Chemistry major with a Specialization in Computing. He is working under the mentorship of Prof. K. N. Houk using computational methods to gain insight into organic chemistry. His research experience would not have been possible without the support of the Arnold and Mabel Beckman Foundation as well as the advice and guidance from the members of the Houk Group.
Oseltamivir, or Tamiflu®, is a potent antiviral medication used to prevent pandemic flu outbreaks. Despite its simple structure, an efficient and environmentally friendly synthesis of oseltamivir remains challenging. We propose a convergent synthesis where all stereocenters of oseltamivir are installed by a late-stage Diels-Alder reaction aided by a designed asymmetric catalyst. Quantum mechanical calculations were carried out to determine the intrinsic reaction preference of the desired carbo-Diels-Alder reaction over other possible hetero-Diels-Alder reactions. The desired regioisomer of the carbo-Diels-Alder reaction is predicted to be the preferred product, but with poor stereoselectivity. Further investigation will characterize interactions which can catalyze this reaction, improve stereoselectivity and design a suitable scaffold to effect asymmetric catalysis.
| Ms. Avalon Dismukes
(pictured above, from left to right: Andrew Lech, grad student. Avalon Dismukes. Dr. Richard Kaner)
Ms. Avalon Dismukes
Mentor: Dr. Richard Kaner
Title: Molybdenum Borides and Phase Relations: Synthesis and Characterization
Avalon Dismukes is a 4th year Chemistry/Materials Science major. She works in the laboratory of Dr. Richard Kaner studying superhard materials and transition metal-boride systems.
Refractory metal borides have recently generated intense interest in materials chemistry. These compounds have been shown to possess many advantageous properties, such as exceptionally high hardness, electrical conductivity, and superconductivity. Higher molybdenum borides (i.e MoB2, Mo2B4, and Mo0.83B3) are currently under exploration as compounds of interest in this category of materials. However, the complicated phase relationships in the molybdenum-boron system complicate the preparation of phase-pure samples. Here we elucidate the phase relations of arc melted molybdenum diboride compounds MoB2 and Mo2B4 around the Mo:2B stoichiometric composition. We show that, by systematically varying the ratio of boron to molybdenum in sub- to super-stoichiometric amounts, samples of exceptionally high phase purity may be prepared. Single phase systems are confirmed by X-Ray Diffraction (XRD) and their grain structure analyzed by scanning electron microscopy (SEM). Detailed analysis of XRD results further reveals a previously unreported lattice defect phase, the structure for which is here proposed. We further demonstrate preferential phase stabilization of the MoB2 structure in ternary solid solutions, in confirmation of previous reports. This work enables further exploration of the properties of molybdenum borides such as hardness measurements, thermogravimetric stability testing, and crystallographic phase design.
Avalon appreciates the support of the Beckman Research Scholarship, and would also like to thank Dr. Richard Kaner, Christopher Turner, Andrew Lech, Dr. Tama Hasson, and the members of the Kaner group for their support and guidance.