2018-19 Alumni

  • Joshua Arriola

    Joshua Arriola

    Email: jtarriol@ucsd.edu
    Undergraduate Institution: UC Santa Barbara
    Program: Chemistry & Biochemistry
    Advisor: Ulrich Muller

    Prebiotic peptides and their interaction with catalytic RNA

    The Muller lab is interested in studying the role catalytic RNA may have played in the early stage of life. The goal of my research project is to determine how peptides aided in the emergence of catalytic RNA.  An in vitro selection in the presence of peptides composed of different prebiotically plausible amino acids will be used to identify any catalytic RNA that require such peptides in order to function. Prebiotically plausible amino acids may differ from natural amino acids in the biophysical characteristics of their interactions with RNA. We are interested in characterizing and quantifying the biophysics of these RNA – peptide interactions as well as determining which residues, if any, are important for catalytic function.

  • Cyrus DeRozieres

    Cyrus DeRozieres

    Email: cderozie@ucsd.edu 
    Undergraduate Institution: UC San Diego
    Program: Chemistry & Biochemistry
    Advisor: Simpson Joseph

    The role of the influenza viral protein NS1 in translation initiation

    Influenza is a seasonal respiratory illness that causes thousands of deaths and billions of dollars in medical expenses and lost earnings every year in the United States alone. It is caused by an RNA virus that is capable of hijacking host cell machinery in order to direct its focus on viral protein production. It accomplishes this with few proteins that perform a wide variety of roles. Non-structural protein 1 (NS1) is a critical protein involved in influenza pathology. NS1 is known to down-regulate the host immune response and increase the rate of translation of its own viral RNAs among other roles. The goal of my research is to investigate how NS1 up-regulates viral protein synthesis by characterizing the protein-protein and protein-RNA interactions involved. Using biochemical and biophysical techniques, I aim to elucidate the mechanism by which NS1 brings translation factors and viral RNAs together. My work will serve to increase our knowledge of this debilitating virus in the hopes of developing new and effective targets for treatment.

  • John Gillies

    John Gillies

    Email: jgillies@ucsd.edu
    Undergraduate Institution: University of Oregon
    Program: Biological Sciences
    Advisor: Samara Reck-Peterson

    Investigation of the biophysical mechanisms governing dynein cargo-specificity

    The microtubule cytoskeleton and its associated motors are responsible for the organization of cellular components necessary for development, cell division, and neuronal function. Cytoplasmic dynein-1 (dynein) is the only minus-end-directed transporter in the cytoplasm, yet is responsible for the transport of dozens of different cargos. This raises a fundamental question: how does dynein achieve cargospecificity? “Activator” proteins, which both activate dynein motility and link dynein to its cargos, play a role in governing cargo specificity. The Reck-Peterson lab recently identified the dynein transport machinery interactome using proteomic methods. My project is centered around two classes of proteins identified using these discovery methods. 1) Candidate non-canonical activators, those that can interact with the dynein transport machinery, but not activate motility. 2) Candidate novel regulatory proteins that may influence which activators are bound to the dynein machinery. I am using biochemical reconstitution and single-molecule motility assays to address these fundamental components of dynein regulation.

  • Riley Peacock

    Riley Peacock

    Email: rpeacock@ucsd.edu
    Undergraduate Institution: Gonzaga University
    Program: Chemistry & Biochemistry
    Advisor: Elizabeth Komives

    Probing the Allosteric Networks of Thrombin

    The clotting cascade is initiated in response to blood vessel trauma, resulting in the downstream activation of the serine protease thrombin. Activated thrombin selectively binds and cleaves various procoagulative substrates, thereby activating them and allowing for the formation of a blood clot. The cofactor thrombomodulin (TM) is found within the cell membrane of the endothelial layer of the blood vessel, and once TM binds to thrombin, thrombin switches its substrate specificity away from procoagulative substrates in favor of the enzyme protein C. Activated PC (APC) initiates the anticoagulative response, resulting in a decrease in the activation of new thrombin molecules. Though the events leading to the switching of thrombin’s substrate specificity have been studied extensively, we are still unsure as to what change occurs within thrombin when TM binds that causes this switch in target preference. Crystallographic evidence suggests that there in not an appreciable difference in conformation between apo-thrombin and TM-bound thrombin, but accelerated molecular dynamics simulations have identified differences between the micro- to millisecond backbone motions of the two species. My work consists of using experimental techniques, such as hydrogen-deuterium exchange and nuclear magnetic resonance, to provide an experimental measure of how the dynamic motions of thrombin are altered by the presence of TM.

  • Kira Podolsky

    Kira Podolsky

    Email: kpodolsky@ucsd.edu
    Undergraduate Institution: Western Washington University
    Program: Biomedical Sciences
    Advisor: Neal Devaraj

    Artificial cells as a model for biological processes

    Liposomes are an essential tool in cellular biology and medicine providing insights into the basic biology of cellular processes, drug delivery, and origin of life. Mimicking “normal” membranes through liposomal modeling research provides fundamental insights into these areas. Other labs have explored simulating basic cellular membrane processes such as membrane division, fusion, and cell growth using synthesized vesicles. My research is focused on creating liposomes that mimic cellular phospholipid bilayers to serve as a model for cell structure and function and to apply these models to biologically relevant systems.

  • Clara Posner

    Clara Posner

    Email: cposner@eng.ucsd.edu 
    Undergraduate Institution: UCLA
    Program: Bioengineering
    Advisor: Jin Zhang

    Elucidating enzyme activity architecture using FLINC biosensor

    Zhang lab focuses on probing the spatiotemporal organization and local activity of various enzymes using genetically encoded biosensors and fluorescence imaging technologies. Our group recently created a new generalizable class of biosensors called Fluorescence fLuctuation Increase by Nonlocal Contact (FLINC) biosensors to directly visualize dynamic biochemical activities on the molecular length-scale in live cells. My project focuses on further enhancing the FLINC class of biosensors by improving the spatial resolution and creating additional protein kinase FLINC sensors.

  • Hannah Rutledge

    Hannah Rutledge

    Email: hrutledge@ucsd.edu
    Undergraduate Institution: Rice University
    Program: Chemistry & Biochemistry
    Advisor: Akif Tezcan

    Determining the conformational gating mechanism in nitrogenase

    Reduced forms of nitrogen are required for life and are necessary for the synthesis of many biological molecules. Nitrogenase is the only known enzyme capable of reducing dinitrogen to ammonia. Nitrogenase contains many metal clusters which are involved in electron transfer, but many aspects of the mechanism remain unknown. The goal of my research is to determine the role of ATP hydrolysis in conformational changes associated with electron transfer between the metal clusters in nitrogenase. To achieve this goal, I am using protein crystallography, characterizing nitrogenase mutants, and searching nitrogeanse sequences for covarying amino acid residues.

  • Bryce Timm

    Bryce Timm

    Email: btimm@ucsd.edu
    Undergraduate Institution: Hamilton College
    Program: Chemistry & Biochemistry
    Advisor: Kamil Godula

    Molecular Origins of Human Extracellular Sulfatase Specificity

    Human endosulfatases (HSulfs), active in the extracellular matrix, cleave sulfate groups from glycosaminoglycan (GAG) polysaccharides with high specificity for the targeted GAG structure, influencing growth factor and cytokine binding. Our project seeks to investigate the molecular interactions underpinning HSulf activity and selectivity. With no crystal structure available, we hope to use synthetic chemistry to delineate and visualize form and function via customizable affinity probes. Once built, the substrate mimic will serve as a tool, used in conjunction with enzymatic modifications and biophysical techniques, to provide structural information regarding the enzyme and the relationship with its targets.

  • Hetika Vora

    Hetika Vora

    Email: hvora@ucsd.edu
    Undergraduate Institution: University of California, Irvine
    Program: Biomedical Sciences
    Advisor: Neal Devaraj

    Targeted Depalmitoylation of N-Ras for Suppression of Oncogenic Signaling Pathways

    Protein S-palmitoylation is a reversible post-translational modification that is present on proteins involved in numerous biophysical processes. Recently, S-palmitoylation has been shown to play an integral role in cancer signaling pathways. Of particular interest is the oncogenic protein N-Ras, which is known to be mutated in many types of cancers. N-Ras is palmitoylated by DHHC palmitoyltransferase, which enables it to transport from the Golgi to the plasma membrane. This association allows the oncogenic N-Ras protein to control a range of signal transduction pathways necessary for cell growth. A potential mechanism to inhibit oncogenic N-Ras activity is to depalmitoylate N-Ras with compounds capable of cleaving endogenous S-palmitoyl modifications. Our group has synthesized a class of molecules capable of chemoselective reactions with long chain thioesters, which could be utilized for in vivo depalmitoylation of N-Ras. We will use live-cell imaging and western blotting to study the molecular biophysics of N-Ras protein interactions with the cell membrane as well as downstream oncogenic signaling pathways affected by the protein modifications. By developing chemical tools capable of in situ protein depalmitoylation, we can better study the effects of post-translational lipidation on the membrane localization and biophysical activity of endogenous N-Ras.

2017-18 Alumni

  • Colin Deniston

    Colin Deniston

    Email: cdenisto@ucsd.edu
    Undergraduate Institution: University of California: Davis
    Program: Chemistry & Biochemistry
    Advisor: Andres Leschziner

    Structural Studies of LRRK2, a key driver of Parkinson’s Disease

    Multiple mutations found in both sporadic and familial cases of Parkinson’s Disease have been mapped to the LRRK2 protein. Despite LRRK2’s importance in the disease phenotype there is still little known of its native functional role and how it changes under disease conditions. In addition, little structural data on LRRK2 is currently published. In order to help address this gap in knowledge I will use cryo-electron microscopy to determine key structural features in both WT and mutant forms of LRRK2 yielding new insights into LRRK2’s various roles in the native cell and during disease progression.

  • Benjamin Jagger

    Benjamin Jagger

    Email: bjagger@ucsd.edu
    Undergraduate Institution: Duquesne University
    Program: Chemistry & Biochemistry
    Advisor: Andy McCammon/Rommie Amaro

    Kinetic rates via milestoning

    The efficacy of a drug is often difficult to predict and therefore many promising drug candidates from in vitro screenings fail when advanced to testing in vivo. Kinetic factors such as the association rate and the residence time (1/koff) of drug-target complexes are important indicators of a drug's in vivo efficacy, particularly in the non-equilibrium environment of the body. The primary barrier to the computer estimation of binding/unbinding kinetics is that these events are relatively rare on the timescales of conventional molecular dynamics simulations. Therefore, we are developing software that allows users to perform multiscale calculations of binding and unbinding kinetics using molecular dynamics, brownian dynamics, and milestoning.

  • Evan Kobori

    Evan Kobori

    Email: ekobori@ucsd.edu
    Undergraduate Institution: UC Berkeley
    Program: Chemistry & Biochemistry
    Advisor: Susan Taylor

    Structural Studies of PKA

    cAMP dependent protein kinase (PKA) is a ubiquitous kinase in mammalian cells that regulates many biological processes and is associated with a variety of diseases and disorders.  Physiologically, PKA exists as a tetrameric holoenzyme consisting of two regulatory (R) subunits and two catalytic (C) subunits.  There are four structurally and functionally non-redundant R isoforms, and the goal of my research is to utilize cryoEM to obtain the structure of the RIβ holoenzyme in a more native state.  This information can further show structural differences between the holoenzymes of the other R isoforms.  Additionally, I am using x-ray crystallography to elucidate the interactions responsible for localizing PKA to the cell membrane and other subcellular environments.

  • Sarah Kochanek

    Sarah Kochanek

    Email: skochane@ucsd.edu
    Undergraduate Institution: Duquesne University
    Program: Chemistry & Biochemistry
    Advisor: Rommie Amaro and Andy McCammon

    Brownian Dynamics of Computationally Designed Proteins Against Influenza

    Influenza virus infection continues to be a major healthcare issue, with 3-5 million cases of severe disease reported and 300,000 to 500,000 deaths worldwide each year. Research efforts in the Amaro Lab have led to the development of a whole-virion influenza model that can be studied computationally. Currently, I am using the “relaxed” structures obtained from whole-virion molecular dynamics simulations as the starting structure for Brownian dynamics (BD) simulations in order to study binding of designed therapeutics. In addition to kinetic information, this study has the potential to reveal information about binding patterns critical for future therapeutic development investigations.

  • Noah Kopcho

    Noah Kopcho

    Email: nkopcho@ucsd.edu
    Undergraduate Institution: University of Texas at Austin
    Program: Chemistry & Biochemistry
    Advisor: Geoffrey Chang

    Characterization of a cerebral amyloid beta efflux transporter

    Excessive amyloid beta peptide within the brain is a hallmark of many neurological disorders. A growing body of evidence suggests that transport mediated efflux across the blood-brain barrier is the primary mechanism which prevents neurodegenerative amyloid beta accumulation. The transporter P-glycoprotein has been shown to play a key role in the removal of cerebral amyloid beta, but precise details related to the structure and function of this transport mechanism remain unclear. My goal is to structurally characterize this interaction using x-ray crystallography and hydrogen-deuterium exchange mass spectrometry. I will further demonstrate the functional relevance of my structural data using cell-based assays in human brain endothelial cells. These studies will lead to a better understanding of the biological machinery which maintains cerebral amyloid beta homeostasis, and the progression of neurodegenerative disease.

  • Adam Maloney

    Adam Maloney

    Email: amaloney@ucsd.edu
    Undergraduate Institution: Elon University
    Program: Chemistry & Biochemistry
    Advisor: Simpson Joseph

    An in vitro model of eukaryotic translation for studies of Fragile X syndrome

    Fragile X syndrome is a common neurological disease that stems from a single genetic defect. This defect produces a nonfunctioning version of the protein FMRP, which is involved in regulation of protein translation in the brain. My research is focused on developing an in vitro model of translation that can be used in biophysical studies of FMRP interacting with the ribosome. By investigating the mechanism through which FMRP inhibits translation we hope to gain an understanding of how translation is fundamentally regulated.

  • Kevin Sweeney

    Kevin Sweeney

    Email: kjsweene@ucsd.edu
    Undergraduate Institution: University of California, Santa Cruz
    Program: Chemistry & Biochemistry
    Advisor: Ulrich Müller

    RNA World Ribozymes Recruiting Peptides as Cofactors

    Due to early origin of life experiments by Stanley Miller and others, we can say that amino acids and short peptides are likely to have existed in the prebiotic world. This would mean that they may have aided in the development of an RNA world. Supporting this idea is the fact that many larger ribozymes use proteins as cofactors today, including the ancient and ubiquitous ribosome. We aim to use a robust, established in vitro selection procedure to identify RNAs that triphosphorylate their 5’-ends using peptide cofactors and then characterize the RNAs and the nature of their interactions with peptides.

2016-17 Alumni

  • Rob Alberstein

    Rob Alberstein

    Email: ralberst@ucsd.edu
    Undergraduate Institution: Carnegie Mellon University
    Program: Chemistry & Biochemistry
    Advisor: Akif Tezcan

    In addition to their diverse array of functionalities, the ability of many proteins to assemble into distinct (and often highly ordered) supramolecular architectures makes them attractive candidates for the development of novel materials. My research is focused on defining rational design strategies which exploit chemically tunable interactions to direct the controlled assembly of proteins into desirable supramolecular structures. Additionally, I develop computational models to simulate our protein materials across large length scales in order to both understand and make predictions about the material properties of these designed protein assemblies.

  • DeeAnn Asamoto

    DeeAnn Asamoto

    Email: dasamoto@ucsd.edu
    Undergraduate Institution: California State University, Long Beach
    Program: Chemistry & Biochemistry
    Advisor: Judy Kim

    Membrane proteins play integral parts in the key processes of life. They act as regulators of communication between the cell and its surrounding environment. Using outer membrane protein A (OmpA) as a model β-barrel protein, I will use fluorescence spectroscopy, including Förster Resonance Energy Transfer (FRET), UV Resonance Raman (UVRR), and bimolecular quenching experiments in order to gain insight into its functions and assembly mechanisms in preformed nanodiscs. Nanodiscs are water-soluble nanoscale phospholipid bilayers that serve as excellent biological membrane mimics which self-assembles integral membrane proteins for biophysical or structural investigation and are well suited for controlled in vitro experiments.

  • Ben Dick

    Ben Dick

    Email: bdick@ucsd.edu
    Undergraduate Institution: University of Rochester
    Program: Chemistry & Biochemistry
    Advisor: Seth Cohen

    Metalloenzymes are a significant portion of the proteome that are clinically relevant targets. I am interested in studying the effect of metal identity in metalloenzymes on inhibitor coordination and subsequent interactions with the active site. To achieve this goal, different metallo isoforms of human carbonic anhydrase and E. coli methionine aminopeptidase will be studied with various potent metalloenzyme inhibitors via X-Ray crystallography to determine inhibitor mode of binding and interactions with the active sites.

  • Sam Kantonen

    Sam Kantonen

    Email: skantone@ucsd.edu
    Undergraduate Institution: Wright State University
    Program: Chemistry & Biochemistry
    Advisor: Michael Gilson

    Molecular simulations have enormous potential for applications in biophysical chemistry, such as drug design and structure prediction. However, simulation results depend on input parameters, in particular the potential function (force field), and poor agreement between experimental measurements and simulation results is often thought to result from inaccuracies in the potential function. My work is focused on measuring the binding thermodynamics of a series of novel host/guest pairs (synthesized in our lab) using both experimental and computational techniques. I can use these two sources of data to assess and improve (using optimization methods) current force fields. In addition to binding data, I also plan on using other sources of data for more complete parametrization, such as solubilities of small molecule crystals and heats of dilution.

  • Charles Lin

    Charles Lin

    Email: chl440@ucsd.edu
    Undergraduate Institution: Ohio State University
    Program: Chemistry & Biochemistry
    Advisor: Ross Walker

    40% of drug candidates that enter clinical trials fail due to poor permeability through cell membranes. Despite this, a detailed understanding of small molecule and peptide membrane permeability has not yet been achieved.  In order to accomplish this, the development of Asymmetric Boundary Conditions would be needed in order to run lipid bilayer Molecular Dynamic simulations involving ionic gradients more accurately and rapidly than previous methods.  With these in place, it will be possible to develop and calculate local diffusion using Potential of Mean Force methods.

  • Ryan Lumpkin

    Ryan Lumpkin

    Email: rlumpkin@ucsd.edu
    Undergraduate Institution: University of Denver
    Program: Chemistry & Biochemistry
    Advisor: Elizabeth Komives

    Ankyrin-repeat and Suppressor of Cytokine Signaling Box (ASB) proteins have been implicated in several cellular signaling pathways, particularly in the ubiquitin-mediated protein degradation. ASB9 serves as the substrate-recognition subunit for a Cullin-RING E3 ligase that tags Creatine Kinase (CK) for degradation by the covalent attachment of Ubiquitin to CK. Previous research identified a binding stoichiometry of one monomer of ASB9 to one dimer of CK. Current efforts aim to obtain a crystal structure of the ASB9-CK complex, followed by the formation of the entire E3 complex in vitro for analysis by Hydrogen-Deuterium Exchange Mass Spectrometry.

  • Jeff Mindrebo

    Jeff Mindrebo

    Email: jmindrebo@ucsd.edu
    Undergraduate Institution: University of Houston
    Program: Chemistry & Biochemistry
    Advisor: Joseph Noel/Michael Burkart

    Primary metabolism describes essential metabolic processes for the viability of an organism, while secondary metabolism provides an organism with advantages that enable further proliferation and survival. Due to the sessile nature of plants, evolutionary flexibility of secondary metabolic enzymes have afforded them the ability to develop a large repertoire of small molecules to aid in their survival and evolution. Vitis vinifera (grapevine) is found on nearly every continent and produces an abundance of secondary metabolites; making it an ideal system for studying how plants evolve new enzymes with unique chemistry in order to have greater fitness in their environments.

  • Sarah Ur

    Sarah Ur

    Email: s1ur@ucsd.edu
    Undergraduate Institution: Cal Poly San Luis Obispo
    Program: Biomedical Sciences
    Advisor: Kevin Corbett

    The MutS Homologs (MSH) have been identified in all organisms from E. coli to humans, and function in the initial recognition of mismatched base pairs in the conserved mismatch repair pathway. In contrast to MSH2-MSH6 and MSH2-MSH3, the MSH4-MSH5 complex does not participate in mitotic mismatch repair, but plays a critical role in meiotic recombination and the segregation of homologous chromosomes during gamete/spore formation. My aim is to reveal how MSH4 and MSH5 interact with chromosomes and components of recombination machinery. By researching the MSH4-MSH5 complex and its downstream partners, we will be able to make a leap in understanding the physical basis of crossover formation.

2015 Alumni

  •  Anastassia Gomez

    Anastassia Gomez

    Email: abgomez@ucsd.edu
    Undergraduate Institution: UC Santa Cruz
    Program: Chemistry & Biochemistry
    Advisor: Nav Toor
    Viroids are non-coding infectious RNAs, typically between 250 and 400 nucleotides long, that infect plants. Viroids do not encode for proteins and yet can cause devastating plant diseases which affect food crops like peach, apple, avocado and many others. My goal is to determine the structure of a viroid and explore the relationship between its tertiary architecture and its infectivity in plants. A combination of x-ray crystallography, biochemistry and in vivo plant studies will be used to determine the mechanism(s) of pathogenesis by viroids and to determine the identity of protein partners of the viroid RNA in vivo.
  •  Chris Fisher

    Chris Fisher

    Email: c7fisher@ucsd.edu
    Undergraduate Institution: Boston University
    Program: Chemistry & Biochemistry
    Advisor: Kamil Godula

    There are numerous pathways through which influenza A can enter a host cell to begin infection. All these entry paths share one feature, which is the initial interaction of the virus with glycoproteins populating cell surfaces. These glycans are abundant and their presentation is difficult to control precluding a detailed understanding of influenza spreading. By remodeling the cell surface with well-defined mimetics of native glycoproteins we gain control over the molecular interactions between the cell surface and the influenza virus. This allows us to control the point and time of viral entry enabling quantitative biophysical analysis of events during influenza entry and spreading throughout tissues and whole organisms.

  • Ryan Lannan

    Ryan Lannan

    Undergraduate Institution: The University of Texas at Austin

    Biophysical determinants of receptor-mediated cellular response variability

    Within a population of cells, the same perturbation can generate a variable cell-to-cell response, which can be viewed as noise in the signal-response function. This noise is due to molecular-scale stochasticity, and in the case of purinergic signaling, is probably mediated by fluctuations in receptor levels. Using live cell imaging techniques, I aim to uncover a link between fluctuations in purinergic receptor levels and the variability of calcium response, thus creating a connection between molecular-scale stochasticity and the accuracy of cellular response.

    Ryan moved with Roy Wollman to UCLA

  •  Chris Lee

    Chris Lee

    Email: ctlee@ucsd.edu
    Undergraduate Institution: University of Virginia Charlottesville
    Program: Chemistry & Biochemistry
    Advisor: McCammon/Amaro

    Influenza membrane glycoproteins, hemagglutinin (HA) and neuraminidase (NA), are thought to mediate viral recognition, attachment, endocytosis, and eventual release. There is frequent mention in literature that the HA and NA binding affinities must be ``balanced'' for optimal viral function. The rational for this hypothesis is that while HA must bind to host-cell surface glycan receptors to promote cell entry, it must not bind so tightly that emerging viral progeny are unable to exit the cell via the enzymatic action of NA. My goal is to use multi-scale computational models of viral surfaces to simulate key events in the host-switching process.

  • Logan Norrell

    Logan Norrell

    Email: lnorrell@ucsd.edu

    Undergraduate Institution: Indiana University

    Evolving group I intron spliceozymes in cells

    The spliceosome is an elegant intron-removal machine that arose abruptly at the time of the origin of eukaryotes. Considering the average human transcript contains 9 introns (comprising a quarter of the DNA content of each cell) and 95% of mamallian multiexon genes undergo alternative splicing, the spliceosome is the gatekeeper to great genetic diversity & regulation.

    What were the evolutionary steps that created the spliceosome’s snRNPs? By evolving our lab’s trans-splicing ribozyme, called the spliceozyme, under a constant genetic background we plan to recapitulate the recognition generalities, domain fragmentations, and protein recruitments observed in the modern spliceosome.

  •  Kristen Ramsey

    Kristen Ramsey

    Email: kmramsey@ucsd.edu
    Undergraduate Institution: Florida State University
    Program: Chemistry & Biochemistry
    Advisor: Komives

    The NF-κB signaling pathway was discovered almost thirty years ago, and from the beginning, it was evident that this pathway was particularly essential in immune responses. Now it is known that NF-κB pathway dysfunction is implicated in many disease states such as various cancers, Alzheimer’s, Parkinson’s, and type 2 diabetes. The dominant form of NF-κB regulation is mediated by its binding to cytosolic inhibitor proteins known as IκBs. My work will seek to biophysically characterize a previously unstudied IκB, IκBε, and probe its structural and conformational dynamics as well as understanding its distinct role in regulating NF-κB.

  • Steve Rees

    Steve Rees

    Email: srees@ucsd.edu

    Undergraduate Institution: St. Mary’s College of Maryland

    Structural Investigation of Membrane Transporters

    Crystallization and structure determination of membrane transporters remain an arduous undertaking, given poor solubility, high hydrophobicity, and resistance to more conventional techniques. My project is multifaceted, studying crystallization of two different transporters and a new synthetic affinity maturation technology. The first involves crystallization of P-glycoprotein, a known xenobiotic efflux pump at the interface between the bloodstream and major organs, with BDE-100, an environmental pollutant persistent in organisms. The second aims to crystallize the Mitochondrial Pyruvate Carrier, a protein complex responsible for the shuttling of pyruvate across the inner mitochondrial membrane. Project three details the development of high-affinity, single-domain antibody binders to a chimeric fusion of the catalytic subunit of protein kinase A, found without exception in a liver cancer subtype primarily targeting children.

  •  Jeff Wagner

    Jeff Wagner

    Email: j5wagner@ucsd.edu
    Undergraduate Institution: Claremont McKenna
    Program: Chemistry & Biochemistry
    Advisor: Amaro

    While well-known informatics methods such as sequence alignment and structural comparison help us detect patterns within structural biology data, the existing methods are by no means exhaustive. Creation of a conceptually unique and meaningful protein relation method has the ability to add a new dimension to the data points in structural biology, thus significantly increasing the impact of available experimental data. I am investigating the use of allosteric pathway detection via molecular dynamics simulations and mutual information analysis to create an “allosteric fingerprint” of a protein. I further propose the collection of these “fingerprints” from each member of a protein family to determine conserved allosteric pathways and similar functional motifs among macromolecular relatives.

2014 Alumni

  • Bryan Arias

    Bryan Arias

    Email: bharias@ucsd.edu
    Undergraduate Institution: University of California, Berkeley
    Program: Chemistry & Biochemistry
    Advisor: Simpson Joseph

    Influenza is a virus that is able to down-regulate host immune response primarily through Non-Structural Protein 1 (NS1). NS1 has been shown to interact with Poly (A) Binding Protein 1 (PAPB1) is human protein known for poly (A) tail processing I want to study the interaction between NS1 and PABP1 to better understand the mechanism using FRET in conjunction with translational assays.

  • David Burban

    David Burban

    Email: dburban@ucsd.edu
    Undergraduate Institution: Arizona State University
    Program: Chemistry & Biochemistry
    Advisor: Patricia Jennings

    Since the discovery of proteins with intrinsically knotted backbones they have become a fascinating area of study, particularly in the field of protein folding, but there are still many mysteries surrounding these once unthinkable folds. Our work is to further illuminate our understanding of knotted proteins by looking at the persistence of the knot in the denatured state and how these proteins fold from untied coil to a fully knotted and folded protein.

  • Lewis Churchfield

    Lewis Churchfield

    Email: lchurchf@ucsd.edu
    Undergraduate Institution: University of Minnesota
    Program: Chemistry & Biochemistry
    Advisor: Akif Tezcan

    Metals are ubiquitously used in the cell as signaling messengers, as structural cofactors, and as catalysts. I am interested in using first principles of design from protein biophysics and coordination chemistry to use metals for directing the ordered assembly of protein complexes. My goal is to use such protein scaffolds as starting points for designing novel metalloenzyme catalysts. In doing so, I aim to expand the range of engineering tools available for designing protein assemblies and enzymes. This work will also furnish model systems suitable for studying the evolution and function of natural protein complexes and metalloenzymes.

  • Christian Cole

    Christian Cole

    Email: cmcole@ucsd.edu
    Undergraduate Institution: Lehigh University
    Program: Chemistry & Biochemistry
    Advisor: Neal Devaraj

    Compartmentalizing of cell-free systems offers a top-down approach in constructing artificial systems. Encapsulation of the transcription-translation cell-free systems in large vesicles is a close biomimic of a living cells. However, continuous expression is limited to a few hours because of insufficient energy renewal systems. To ameliorate this problem we look at the flux of small molecules into our bioreactor from "feeding buffers”.

  • Jessica Peters

    Jessica Peters

    Email: jkpeters@ucsd.edu
    Undergraduate Institution: Georgia Tech
    Program: Chemistry & Biochemistry
    Advisor: Nav Toor

    The spliceosome is the RNP responsible for the removal, or splicing, of introns from pre-mRNA to form mature mRNA ready for translation in eukaryotes. The size and complexity of this RNP has made it difficult to study structurally. Currently, the only crystal structure that exists for the spliceosome is of the U1 RNP. However, it is known that the spliceosome active site is formed from two snRNAs, U2 and U6, and follows a similar splicing pathway to that of group II introns in which a lariat RNA is formed. I am currently working to determine the structure of the complex formed between these two snRNAs and how they function to catalyze splicing.

  • Jamie Schiffer

    Jamie Schiffer

    Email: jschiffe@ucsd.edu
    Undergraduate Institution: Boston University
    Program: Chemistry & Biochemistry
    Advisor: Rommie Amaro

    Elevated levels of creatine kinase (CK) can nearly double the survival rate after heart failure in mouse models. In the cytoplasm, CK is inhibited and targeted for degradation by ankyrin repeat and suppressor of cytokine signaling protein box 9 (ASB9). I am interested in understanding the dynamics and thermodynamics of ASB9 in binding to CK and using ensemble-based drug design to develop a small molecule inhibitor that disrupts the ASB9-CK interaction. This would elevate CK levels in the cell and restore heart cells to a healthy energy state after heart failure.

  • Bryan Stephens

    Bryan Stephens

    Email: bsstephens3@gmail.com
    Undergraduate Institution: University of New Mexico
    Program: Biomedical Sciences
    Advisor: Tracy Handel

    C-X-C motif chemokine receptor 4 (CXCR4) is a class A GPCR and is the receptor for C-X-C motif chemokine 12. CXCR4, like many other class A GPCRs, is known to form both homodimers and heterodimers, as well as higher order oligomers. We are attempting, using a combination of site-directed mutagenesis with various cellular chemokine receptor activation assays and biophysical methods, to determine the structural causes as well as the functional effects of CXCR4 dimerization.

  • Nicholas Tiee

    Nicholas Tiee

    Email: ntiee@ucsd.edu
    Undergraduate Institution: Rice University
    Program: Chemistry & Biochemistry
    Advisor: Patricia Jennings

    Previous studies on the Interleukin-36 family of receptors have shown that they are important in the regulation of psoriasis. Specifically, disease mutants in IL36Ra that cause a life threatening form of psoriasis have been identified in humans, and these are thought to be the result of misfolding. Thus in order to understand the cause of the misfolding, a biophysical characterization of IL36Ra is necessary. By using NMR, mass spectrometry, as well as a classic suite of kinetics and thermodynamics experiments, the mutant can be characterized.

  • Alan West

    Alan West

    Email: a2west@ucsd.edu
    Undergraduate Institution: Tufts University
    Program: BMS
    Advisor: Corbett

    The careful regulation of homologous recombination in meiosis I is necessary for proper chromosome segregation and the production of viable gametes. As such, the process is regulated by the meiotic recombination checkpoint. The protein Hop1 has been shown to play a major role in the checkpoint, however the mechanism by which it is able to relay the checkpoint signal remains unclear. My goal is to create crystallographic models of Hop1, and its binding partners, to reveal potential protein interaction surfaces, and provide insight into how conformational changes in Hop1 might regulate recombination. These structures will form the basis of biochemical and genetic assays to determine how specific mutations effect meiotic progression and gamete viability.

  • Clifford Woodford

    Clifford Woodford

    Email: cwoodfor@ucsd.edu
    Undergraduate Institution: Trinity University
    Program: Chemistry & Biochemistry
    Advisor: Tsien

    A number of cell types we are interested in understanding, most notably neurons, propagate signals electrically by membrane polarizing and depolarizing. Optical detection of these signals through voltage sensitive fluorescent dyes is a promising tool in part due to wide spatial and temporal detection as well as limited systemic perturbation. I am currently working on developing organic small molecules containing a fluorophore whose quantum yields are modulated by a photo-induced electron transfer based quenching mechanism dependent on the electric field across the membrane containing the dye to provide an optical tool able to detect membrane potential changes in biological systems.

2013 Alumni

  • Ignacio Lopez

    Ignacio Lopez

    Email: ilopezpe@ucsd.edu
    Undergraduate Institution: San Francisco State University
    Program: Chemistry & Biochemistry
    Advisor: J. Kim
  • Hoang Thien Nguyen

    Hoang Thien Nguyen

    Email: htnguyen@ucsd.edu
    Program: Chemistry & Biochemistry
    Advisor: Viadiu
  • Christopher Pierse

    Christopher Pierse

    Email: cpierse@physics.ucsd.edu
    Program: Physics
    Advisor: Dudko