Current Trainees

Trainees appointed in 2018

  • Bryce Ackermann

    Bryce Ackermann

    Email: beackerm@ucsd.edu 
    Undergraduate Institution: University of California: Davis
    Program: Chemistry & Biochemistry
    Advisor: Galia Debelouchina

    Interrogating genome packaging

    The human genome is compacted into cell nuclei in the form of chromatin, a giant polymer of protein and DNA that spatially organizes to allow for timely execution of nuclear processes. On a crude level, chromatin separates into transcriptionally hindered and transcriptionally active regions dependent on local chemical modifications and chromatin interacting proteins that lead to differential compaction densities. The effects can be visualized at the nuclear level but difficult to study in molecular detail. Therefore, our lab will focus on advancing methodology for structural biology in cells. We will develop chemical biology and nuclear magnetic resonance spectroscopy tools to investigate the structure and dynamics of differentially packaged chromatin in human cells.

  • Joshua Corpuz

    Joshua Corpuz

    Email: jccorpuz@ucsd.edu 
    Undergraduate Institution: UC San Diego
    Program: Chemistry & Biochemistry
    Advisor: Michael Burkart

    Understanding PCP-mediated protein-protein interactions in NRPS systems.

    49% of FDA approved anticancer drugs are natural products or derivatives of natural products. Natural products also have a variety of bioactivities in humans and other organisms, including antibiotic, antiviral, and antifungal activities. A major family of enzymes that synthesize these natural products are nonribosomal peptide synthetases (NRPS). Since they are prevalent in natural product synthesis, NRPSs have become targets for protein engineering to create novel pharmaceutical drugs and novel biosynthetic pathways of the drugs.

    NRPS are modular enzymes that act like an assembly line to create peptide products.One of the core domains in the NRPS is the peptidyl carrier protein (PCP); its role is to transport the growing peptide chain between multiple domains in a specific order. The molecular mechanism by which the PCP recognizes the different domains is not well understood. My project helps advance our understanding of PCP-mediated protein-protein interactions through biochemical and structural analysis of the PCP and partner proteins. With increased understanding of the interactions, we can better engineer NRPS systems to create novel pathways and pharmaceutical drugs.

  • 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.

  • Mounir Fizari

    Mounir Fizari

    Email: mfizari@ucsd.edu 
    Undergraduate Institution: Univ. of Illinois Urbana-Champaign
    Program: Physics
    Advisor: Doug Smith

    Single molecule studies of bacteriophage phi29 DNA packaging

    A critical step in the lifecycle of many bacteriophages and some eukaryotic viruses is the packaging of the viral genome into a prohead by an ATP-powered molecular motor. The bending rigidity and electrostatic self-repulsion of the DNA and the entropic penalty of confinement make this process energetically unfavorable. In bacteriophage phi29, previous studies have found evidence that the nonequilibrium dynamics of the confined DNA affect packaging by providing a resistive load on the motor and triggering an allosteric feedback mechanism. Using optical tweezers to monitor the force exerted and rate of DNA packaged by individual phi29 complexes, I will vary the prevalence of nonequilibrium conformations by reducing the rate of packaging, nicking the genome to reduce the DNA’s bending rigidity, and using a larger mutant phi29 prohead to probe the relationship between nonequilibrium conformations and packaging kinetics.

  • Sonjiala Hotchkiss

    Sonjiala Hotchkiss

    Email: sonjiala@ucsd.edu 
    Undergraduate Institution: Univ. of New Orleans
    Program: Chemistry & Biochemistry
    Advisor: Gourisankar Ghosh

    My proposed research will focus on characterizing and elucidating how the binding of small molecule inhibitors of human IKK2/b affect its protein dynamics and therefore its function. IKK2 is a catalytic subunit of the heterotrimer IkB Kinase (IKK). The two additional subunits are IKK1/a, also a catalytic subunit, and NF-kB essential modulator (NEMO/IKKg), a regulatory subunit. IKK is an essential kinase in the activation pathway of the nuclear factor kB (NF-kB) family of transcription factors. This family consists of five proteins that can combine to form homo- or hetero-dimers: p65/RelA, p50, p52, c-Rel, and RelB. The NF-kB dimers remain inactive in most cells which can be activated by a large number of stimuli including cytokines, pathogens and radiation though a cascade of reactions that mostly starts at the cell surface. NF-kB activation occurs along two pathways, the canonical pathway and the noncanonical pathway. As an enzyme in the canonical pathway, IKK2 is activated by phosphorylation of its activation loop serines, S177 and S181.

  • Dominic McGrosso

    Dominic McGrosso

    Email: dmcgross@ucsd.edu 
    Undergraduate Institution: CSU San Marcos
    Program: Biomedical Sciences
    Advisor: Geoffrey Chang

    My current research in the lab of Dr. Geoffrey Chang utilizes directed evolution techniques to generate and characterize small molecule binders to investigate the physical properties and biomolecular structure of small molecule pollutants and their binders. Small molecules, especially pollutants such as polycyclic aromatic hydrocarbons, polybrominated diethyl ethers, and triclosan, have been found in many environments including those essential for humans, like water used for drinking, ocean fisheries, and farmland. Many of these molecules have been demonstrated to have negative effects on human health and environmental robustness. There are multiple methods used to detect small molecule pollutants in use today, including mass spectrometry and other various chromatographic and spectrophotometric methods, however each of these methods have inherent weaknesses that preclude them from direct field applications.

  • Elizabeth Porto

    Elizabeth Porto

    Email: eporto@ucsd.edu 
    Undergraduate Institution: Univ. of Missouri - Kansas City
    Program: Chemistry & Biochemistry
    Advisor: Alexis Komor

    Expanding the Scope of DNA Base Editing

    The use of the clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR-associated protein 9 (Cas9) system has become the standard method for genome editing. The system relies on the ability of Cas9 to introduce a double strand break (DSB) at a desired DNA sequence, followed by precise repair from a donor template through homology-directed repair (HDR). However, DSB-reliant genome editing results in stochastic mixtures of unwanted genome modifications, making it less reliable for commercial use. Base editing is an alternative technique that enables the direct, irreversible conversion of a single target DNA base in a precise, programmable manner without introducing a DSB or requiring a donor template. This methodology is currently limited in its scope by only facilitating C•G to T•A or A•T to G•C base pair conversions. My project is focused on engineering new DSB-free genome editing tools that expand the types of DNA base pair transformations researchers can cleanly and efficiently introduce into the genome of living cells. This project will advance basic scientific understanding of genome editing enzymes as well as accelerate novel organism engineering efforts, with the potential to be used commercially in improving therapeutic efforts.

  • Clara Posner

    Clara Posner

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

    Elucidating enzyme activity architecture using FLINC biosensors

    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.

  • Douglas Zhang

    Email: doz023@ucsd.edu 
    Undergraduate Institution: UCLA
    Program: Chemistry and Biochemistry
    Advisor: Thomas Hermann

    Nanoengineering takes advantage of the interactions of materials at the nanometer scale to create functional nanostructures. Nucleic acids have traditionally been prized for their role in carrying genetic information, however, their ability to self-assemble into a variety of shapes based on simple Watson-Crick base-pairing rules makes nucleic acids an ideal material for nanotechnology. Nucleic acid nanotechnology has been shown to have applications    ranging    from    molecular    electronics   to

    nanomedicine1. DNA nanotechnology has seen the most development due in large part to the breakthrough of DNA origami2, which enabled the creation of arbitrarily shaped nanostructures. However, the creation of large DNA nanostructures is nontrivial and yields of structures can be low. RNA nanotechnology exploits the intrinsic ability of RNA to naturally fold into complex structures, such as pseudoknots and multiway junctions3, which can make the design of nanostructures much simpler than DNA nanotechnology. Unfortunately, long strands of RNA are prone to degradation.

    It is becoming apparent that a hybrid approach, combining DNA with RNA, in the construction of nanostructures may be able to capitalize on the strengths of DNA and RNA while minimizing their drawbacks. Such an approach could combine RNA as structurally more complex architectural joints with DNA as robust functional modules, resulting in the  programmable  self-assembly  of  a  variety  of    nano-constructs. The Hermann lab has created a native PAGE screening strategy that has already been used to discover and validate several self-assembling DNA/RNA nano-shapes. Much work remains to be done to develop these hybrid DNA/RNA nano-shapes into robust programmable platforms for applications in molecular recognition, sensor and catalyst development as well as protein interaction studies.

Trainees appointed in 2017 and reappointed in 2018

  • 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.

  • 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.

  • 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.