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The Undergraduate Research & Teaching
Scholars Program

2009-2010


        



Ms. Dorsa Beroukhim
Ms. Phyllis Huang
Ms. Yuri Shindo
Ms. Kim Ngan Tu
Ms. Margaret Wang

Ms. Dorsa Beroukhim
Mentor: Dr. Stephanie White
Funding: Ehrisman Scholar
Title: Expression of Autism Susceptibility Gene, Caspr2, in a Model for Vocal Learning

Dorsa Beroukhim is a fourth year student majoring in Neuroscience. She works with Dr. White in the department of Physiological Sciences and is currently researching the expression of CASPR2, identified as an autism susceptibility gene, in the zebra finch brain during development.

The underlying cause of Autism Spectrum Disorder (ASD), characterized by social and behavioral difficulties often with language impairments afflicting more than 500,000 children in the United States, is largely unknown. Before we can fully understand the neural basis of this disorder, a deeper understanding of how the brain learns and produces language is necessary. The White lab investigates the genetic and neural correlates of song learning by targeting brain nuclei dedicated to song learning and production behavior.  

CASPR2 colocalizes with potassium channels at the juxtaparanodes of myelinated axons. (Poliak et al., 2003).  It has been observed that in CASPR2 knock down mice, potassium channels were mislocalized, suggesting that CASPR2 is important in clustering the potassium channels to the juxtaparanodal region. Disruptions to this process may lead to altered neural activity, which may explain the behavioral and language changes observed in autistic children with the mutation. 

The focus of Dorsa's project is to analyze CASPR2 expression and its role at critical time points in song learning development in zebra finch.  By making use of immunohistochemistry and optical imaging techniques, she will be able to characterize Caspr2 expression in relation to song learning and speech, which will further our understanding of the genetic basis of language, and thus autism. 

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Ms. Phyllis Huang
Mentor: Dr. Joseph Watson
Funding: Wasserman Scholar
Title: S-Glutathiolation Activity in Mouse Models of Parkinson’s Disease

Phyllis Huang is a fourth-year Neuroscience major and Atmospheric and Oceanic Sciences minor at UCLA. She began working in Dr. Joe Watson’s lab in Winter 2008 and has been studying the mechanism of Glutathiolation in response oxidative stress in Parkinson’s disease (PD). Prior to working with Dr. Watson, Phyllis worked for a summer in the Neuropsychiatry and Behavioral Medicine Animal Lab at UCSD, assisting Dr. David Feifel in developing a rat paradigm for social discriminative characteristics of schizophrenia. She also worked with Dr. Scott Fears at the Ahmanson Lovelace Brain Mapping Center, analyzing brain structures of human and Rhesus Monkeys with Schizophrenic symptoms. She is looking forward to starting her senior research project with Dr. Watson as well as tutoring Atmospheric and Oceanic Science courses at Academic Advancement Program (AAP).

Phyllis’s research is based on previous studies showing that glutathione (GSH) acts as the cell’s major reductant system in the degradation of oxidative and nitrosative radicals and S-glutathiolation of cysteine thiol moieties important for regulating gene expression, protein synthesis, and apoptosis. GSH is the most abundant non-protein thiol composed of a tripeptide of glutamate, cysteine, and glycine. Found in cytosol and mitochondria, this small molecule functions in three manners. It can non-enzymatically neutralize free radicals such as superoxide and hydroxyl radicals by oxidizing to glutathione disulfide. Enzymatically, glutathione work in conjunction with glutathione peroxidase and reductase to remove peroxides responsible for mitochondrial dysfunction. Additionally, S-glutathiolation of sulfhydryl groups form mixed disulfides which prevent irreversible loss of function due to oxidative damage of proteins, lipids, and DNA, thereby providing a neuroprotective, compensatory response to oxidative stress often associated with PD.

In discovering the nature of S-glutathiolated proteins, the project will utilize mitochondrial isolation techniques to study S-glutathoilated proteins as well as selective immunocapture of mitochondrial Complexes (I-IV) in the electron transport chain. The first approach will compare S-glutathiolated proteins in cytosolic, mitochondria, and synaptoneurosome subcellular fractions between WT and ASOTg mice. The second method aims to elucidate the interactions of GSH with specific mitochondrial Complexes. This approach will use a Mitochondria Immunocapture kit to quantify the amount of mixed protein disulfides and glutathione disulfide proteins in each Complex. Through these two experimental approaches, Phyllis hopes to elucidate the mechanism of glutathiolation and its contribution to PD pathophysiology.

Phyllis would like to thank Dr. Watson for the amazing opportunity to learn about the field of Parkinson’s research hands on. She would also like to thank the members of Watson lab, especially Tim Ando for his generous guidance and support. She is very thankful for Dr. Feifel’s and Dr. Fears’s supervisions in previous research projects. Moreover, she is very grateful to Emmanuel Owaka and the AAP program for the opportunity to work academically with fellow UCLA students. Most importantly, she would like to extend her gratitude to Tama Hasson, the Undergraduate Research Center, and the Wasserman Family for their support and kindness.

 

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Ms. Yuri Shindo
Mentor: Dr. Ren Sun
Funding: Wasserman Scholar
Title:
The Role of TATA Binding Protein in Late Gene Regulation of Murine Gammaherpesvirus-68

Yuri Shindo is currently a fourth year student majoring in Microbiology, Immunology, and Molecular Genetics. She works with Dr. Ren Sun and Dr. Ting-Ting Wu studying the regulation of late gene expression in murine gammaherpesvirus 68 (MHV-68).

Members of the gamma subfamily of herpesviruses, including the Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus, are associated with lymphomas and other malignancies. In order to study these human gammaherpesviruses, MHV-68 is used as a model system. In MHV-68, late gene transcription occurs in tandem with viral replication and leads to the expression of structural proteins necessary for viral assembly. Although MHV-68 has been extensively studied in light of immediate early and early gene expression, how the virus is able to regulate late gene expression following genome replication is currently unclear.

Previous studies by the Sun lab have shown that RNA polymerase II is not recruited to herpesviral late gene promoters in MHV-68 mutants lacking one of five open reading frames (ORF18, ORF24, ORF30, ORF31, or ORF34). Because the TATA binding protein (TBP) is part of the RNA polymerase II preinitiation complex, it is possible that the association between TBP and the TATA box sequences of late gene promoters regulates which DNA sequences can be transcribed. Chromatin immunoprecipitation (ChIP) assays will be used in order to determine the association of TBP with promoters of viral late genes in cells infected with wild-type and mutant MHV-68. This assay may help elucidate the mechanisms of transcriptional regulation in MHV-68. By discovering how to disrupt the mechanisms of late gene expression in MHV-68, we may be able to lean how to attenuate this murine virus and ultimately its human homologues as well.

Yuri would like to thank Dr. Ren Sun and Dr. Ting-Ting Wu, inspirational mentors who constantly encourage academic curiosity and creativity. She is also very appreciative of the rest of Sun lab for their continual guidance and advice. She would like to thank the Academic Advancement Program, Emmanuel Owaka, and her amazing students for the rewarding experience of helping fellow students. Yuri is grateful to the Undergraduate Research Center and the Center for Academic and Research Excellence for the wonderful opportunity to combine research and tutoring. Lastly, she would like to thank the Wasserman family for their generous support.

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Ms. Kim Tu
Mentor: Dr. Patrick Harran
Funding: Wasserman Scholar
Title: Synthesis of a Smac (Second mitochondria-derived activator of caspases) mimic molecule

Picture coming soon!

Kim Tu is a fourth year Chemistry student. She has been working in Dr. Patrick Harran’s research lab since Spring 2008. She is very interested in the organic synthesis of biological molecules that can mimic activities inside human body. Her project focuses on the synthesis of a Smac (Second mitochondria-derived activator of caspases) mimic molecule that can compete with the binding of the Smac peptide to the Bir domain of different forms of IAP and promote cell apoptosis. Second mitochondria-derived activator of caspases (Smac) has been found to sensitize for apoptosis and therefore inhibit IAPs activity by protein-protein interactions with the N-terminal four residues of Smac. Specifically, Smac interacts with a groove in Bir-2 and Bir-3 domains, thus reactivates apoptosis. However, in order to have the highest efficiency towards binding with IAPs, especially XIAP, the dimer Smac mimic needs to respond accordingly to the different forms of XIAP, where the groove in domain Bir-2 and Bir-3 changes conformation. This requires the dimer Smac mimic to be attached to some scaffold that can have many possible conformations, and fullerene C60 is the choice here. N-(4-hydroxyohenyl) glycine and formaldehyde are reacted with fullerene C60 in toluene to produce the bis-adduct that can be used as a scaffold for the dimer Smac mimic. The advantage of using fullerene is that it can give as many as eight possible isomers for the bis-adduct, and therefore may increase the Smac mimic affinity to binding with Bir-2 and Bir-3 domain. The main challenge of the project is to be able to isolate all eight isomers with a relative amount for each of them that can be used to undergo the attachment of Smac mimic molecule onto the functionalized fullerene. This can be achieved using the HPLC system provided in the research lab. Our purpose is to test the biological activity of all eight different Smac mimic-attached isomers in cells and determine whether they are appropriate for therapeutic treatment for cancer.

Besides doing research, Kim is also an AAP tutoring for Chemistry 30B, organic chemistry starting in the fall 2009. She has been working in the chemistry lab support since fall 2008 and still continues this year. Kim would like to thank Dr. Patrick Harran for giving her the chance to do research and develop her interest in organic chemistry. She would also like to thank the Academic Advancement Program for letting her become a tutor where she can help out other students and make new friends.

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Ms. Margaret Wang
Mentor: Dr. Robert Wayne
Funding: Miller Scholar
Title: Discerning Hybridization Events between the European Mink and European and Steppe Polecats

Margaret Wang is a fourth-year Biology major with a minor in Biomedical Research. She has been working in Dr. Robert Wayne’s lab since Spring of 2008. In the summer of 2008, she worked in the Wayne lab with Dr. Koepfli to reconstruct the species-level phylogeny of the Carnivora under the Whitcome Fellowship. She has also worked with Dr. Koepfli to understand the biogeographical history of East and South African populations of Black-Backed Jackals ( Canis mesomelas) by looking at intron substitution and indel polymorphisms of 20 genetic loci. She will be finishing up this project after collecting data on two more mitochondrial loci, and analyzing the results. She is excited to start her senior research project, as well as tutor Life Sciences 3, her favorite Life Sciences class, for AAP.

Her project involves discerning species informative loci of the European Mink (Mustela lutreola), a highly endangered mammal, that is undergoing hybridization with the sympatric European Polecat (Mustela putorius) and Steppe Polecat (Mustela evermannii), for lack of available mates. Interbreeding acts as a sink that leads to a loss of the unique genetic pool of M. lutreola, and also leads to outbreeding depression. By looking at fixed loci where pure-breed Minks or Polecats would appear as homozygous, and hybrids as heterozygous, we can easily determine hybrids from pure-breeds, which might not be possible looking only at physiology. To easily distinguish pure-breeds from hybrids directly affects captive breeding and reintroduction conservation programs.

Margaret would like to thank Dr. Wayne for the opportunity to work in his lab, and the whole Wayne lab for their supportive and welcoming attitude, making lab an easy and fun environment to work in. She thanks Emmanuel Okawa for giving her the chance to tutor UCLA students, which she finds very rewarding. Most importantly, she would like to thank Dr. Klaus-Peter Koepfli, for his mentorship, encouragement, patience, knowledge and kindness, without which nothing would have been possible.

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Profiles of Students