Current Trainees

Trainees appointed in 2016

  • 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: Geoffry 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.

Trainees appointed in 2015 and reappointed in 2016

  • 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.