Current Trainees

Trainees appointed in 2017

  • Joshua Arriola

    Joshua Arriola

    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.

  • John Gillies

    John Gillies

    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

    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

    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.

  • Hannah Rutledge

    Hannah Rutledge

    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

    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

    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.

Trainees appointed in 2016 and reappointed in 2017

  • Colin Deniston

    Colin Deniston

    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

    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

    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

    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

    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

    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

    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.