Ingrid Devries
Advisor:  E. Komives
Chemistry & Biochemistry
Year:  3
Jeff Noel
Advisor:  J. Onuchic
Physics
Year:  2
 
    Mikolai Fajer
Advisor: A. McCammon
Chemistry & Biochemistry
Year:  2
Andro Rios
Advisor:  Y. Tor
Chemistry & Biochemistry
Year:  2
 
    Greg Hannum
Advisor: T. Ideker

Year:  2
Eric Salgado
Advisor:  A. Tezcan
Chemistry & Biochemistry
Year:  3
 
    Michael Jamros
Advisor:  P. Jennings
Chemistry & Biochemistry
Year:  2
Diana Schlamadinger
Advisor:  J. Kim
Chemistry & Biochemistry
Year:  3
 
  Ariane Jansma
Advisor:  T. Handel
Chemistry & Biochemistry
Year:  4
Yan Wang
Advisor:  S. Opella
Chemistry & Biochemistry
Year:  2
 
  Andrew Markley
Advisor:  J. Dixon
Chemistry & Biochemistry
Year:  3
     
   
  Benjamin Andrews
Advisor:  P. Jennings
Chemistry & Biochemistry
Year:  5
Byron Hetrick
Advisor:  S. Joseph
Chemistry & Biochemistry
Year:  5
 
  Cecilia Cheng
Advisor:  S. Taylor
Chemistry & Biochemistry
Year:  4
Stanley Howell
Advisor:  S. Opella
Chemistry & Biochemistry
Year:  5
 
  Audrey Fischer
Advisor:  M. Montal
Biology
Year:  5
Jeffrey Kearns
Advisor:  A. Hoffman
Chemistry & Biochemistry
Year:  4
 
  Derek Fuller
Advisor:  D. Smith
Physics
Year:  4
Anna-Clare Milazzo
Advisor:  Xuong
Physics
Year:  6
 
  Ilya Gertsman
Advisor:  J. Johnson
Chemistry & Biochemistry
Year:  5
Paul Whitford
Advisor:  J. Onuchic
Physics
Year:  5
 
 

 
    Carla Cervantes
Advisor:  E. Komives
Chemistry & Biochemistry
Year:  5
Cathrina Salanga
Advisor:  T. Handel
Chemistry & Biochemistry
Year:  4
   
 

Amy Davenport
Advisor:  E. Komives
Chemistry & Biochemistry
Year:  2
     
 
 
     
  Benjamin Andrews

bandrews@ucsd.edu
Department:  Chemistry & Biochemistry
Advisor:  Pat Jennings
Year:  4

 
  The protein folding problem is an issue that has gained attention since the sequencing of the human genome. How can a protein fold into a unique 3-Dstructure from the amino acid sequence; can we predict protein structure from an amino acid (and thus, DNA) sequence? Currently I am working on the folding of GFP, a widely used molecular marker. Using both computational modeling techniques as well as experimental stability and folding determinations, we hope to improve on the folding rate of GFP and related variants in its use as a protein folding & stability reporter.  
     
  Cecilia Cheng

C2cheng@ucsd.edu
Department:  Chemistry & Biochemistry
Advisor:  Susan Taylor
Year:  3

 
     
     
  Ingrid Devries

idevries@ucsd.edu
Department:  Chemistry & Biochemistry
Advisor:  Elizabeth Komives
Year:  2

 
  I am studying the folding and stability of the ankyrin repeat protein IkBa, which undergoes two folding transitions.  The first folding transition occurs when IkBa is free, the second appears to be coupled to binding to NF-kB.  Based on simulations, we have identified a number of mutation that should affect the first or second folding transitions.  I will characterize the folding behavior of these mutants by determining the folding phi values to help determine the physical characteristics of ankyrin repeat proteins that causes them to fold.  
     
  Mikolai Fajer

mfajer@gmail.com
Department:  Chemistry & Biochemistry
Advisor:  Andy McCammon
Year:  2

   
     
     
  Audrey Fischer

Audreyf@ucsd.edu
Department:  Biology
Advisor:  Maurice Montal
Year:  5

 
  I am studying the ion channel properties of the botulinum neurotoxin (BoNT), the most potent toxin known.  BoNT is a dichain peptide:  the heavy chain (100kD) forms an ion channel under endosomal conditions to 'chaperone' the light chain (50kD) protease and release it to the cytoplasm where it can cleave its substrate SNARE protein.  One of the most intriguing properties of the BoNT is its conformational change triggered by a pH change.  At pH 7.0 the holotoxin is inert and harmless; however lowering to endosomal pH 5.5 changes the heavy chain conformation into an active ion channel and partially unfolds the light chain.  The heavy chain channel facilitates the translocation of the light chain across the membrane where it is released. A major goal of this project is to understand the novel modality of BoNT chaperone activity: protein conducting/translocating channels.  We have developed a neuronal system to characterize the channel and chaperone activities of BoNT under conditions which closely emulate those prevalent at the endosome, and which are relevant to the neurotropism and neuroparalytic effects of BoNTs.  We have also developed an in-vitro fluorescence assay to monitor BoNT enzymatic activity resulting from translocation of the light chain by the heavy chain channel.  
     
  Derek Fuller

dfuller@physics.ucsd.edu
Department:  Physics
Advisor:  Doug Smith
Year:  4

 
  I will be using optical tweezers to study packaging of the viral genome in the capsid of Phi29 and possibly other bacteriophages.

Publications:

  •  D. N. Fuller, G. J. Gemmen, J. P. Rickgauer, A. Dupont, R. Millin, P. Recouvreux and D. E. Smith.  A general method for manipulating DNA sequences from any organism with optical tweezers.   Nucleic Acids Research, 2006, Vol. 34, No. 2 e15.
 
     
  Ilya Gertsman

gertsman@ucsd.edu
Department:  Chemistry & Biochemistry
Advisor:  J. Johnson
Year:  4

 
  A number of bacteriophage and viruses (including lambda and Herpes) assemble into a precursor capsid that undergoes a maturation upon nucleotide packaging.  We are studying the structure and expansion mechanism of HK97, a lambda like phage.  The structure of the Procapsid is being studied using x-ray crystallography while intermediates of the expansion pathway are being probed with Hydrogen/Deuterium exchange coupled with mass spectrometry. The goal is to understand the properties of the HK97 fold and protein-protein interactions that facilitate the massive capsid reorganization and expansion the phage undergoes.  
     
  Greg Hannum

ghannum@ucsd.edu
Department: 
Advisor:  T. Ideker
Year:  2

   
     
     
  Byron Hetrick

bhetrick@chem.ucsd.edu
Department:  Chemistry & Biochemistry
Advisor:  Simpson Joseph
Year:  4

 
  Our lab studies the mechanism of translation in the eubacterial ribosome.  The ribosome is the most common target for antibacterial drugs so, understanding the mechanism of protein synthesis is essential in understanding how many current drugs work and will aid in the design of future antibiotics.  The focus of my research is understanding how the ribosome selects the correct tRNA based upon the interaction of the codon of the mRNA with the anticodon of the tRNA in the A-site of the ribosome.  I an studying the kinetic mechanism of A-site selection using pre-steady state kinetics and fluorescence-based techniques.  
     
  Stanley Howell

schowell@ucsd.edu
Department:  Chemistry & Biochemistry
Advisor:  S. Opella
Year:  4

 
  The ability to obtain high-resolution structural information on integral membrane proteins associated with a bilayer environment continues to represent a bottleneck by conventional structure determination methodology.  These lipo-protein mixtures have proven difficult to crystallize and the size of the ensemble creates long correlation times, drastically reduces the effectiveness of solution-state NMR techniques for NOE based structure determination.  The current focus of research is the development of NMR techniques for the observation and utilization of anisotropic interactions for structure determination of membrane proteins.  The integral membrane proteins of the mer operon: MerF (81 residues), MerT (116 residues), and MerC (153 residues), are being applied as test systems for developing the necessary methodology for expanding current techniques toward polytopic proteins of increasing complexity as well as the elucidation of the mechanistic details of the bacterial mercury detoxification system.  
     
  Michael Jamros

mjamros@ucsd.edu
Department:  Chemistry & Biochemistry
Advisor:  Pat Jennings
Year:  2

   
  Protein kinases play a prominent role in cell growth and therefore are promising targets for drug design for combating various cancers. The Src family of tyrosine kinases are an important group of enzymes that are up-regulated in many cancers, notably breast and colon cancer. These enzymes present an attractive chemotherapeutic target. Due to the abundance of kinases, finding unique binding surfaces is necessary in the design of selective inhibitors. To find these binding surfaces it is important to understand how the Src enzymes are naturally regulated and how they use molecular cross-talk to engage large substrate proteins. Two functionally distinct enzymes, Csk (C-terminal Src kinase) and Chk (Csk homologous kinase), down-regulate the Src kinases. While both Csk and Chk down-regulate Src and have a high homology (55% identity), the two differ in expression pattern, subcellular localization, and substrate selectivity. I am characterizing the interaction observed between Chk and Src by investigating the molecular factors that control this interaction and impact the mechanism of Src down-regulation. Additionally, I am working to further elucidate how Csk operates in regulating Src.
 
 
     
  Ariane Jansma

ajansma@ucsd.edu
Department:  Chemistry & Biochemistry
Advisor:  T. Handel
Year:  3

 
  My Current research project is focused in several areas. The first part involves the expression and structural characterization of the chemokine Mec using 3- and 4-dimensional heteronuclear NMR experiments as well as X-ray crystallography if the protein is amenable. The second part involves the expression and biophysical analysis of the 7-transmembrane chemokine receptors D6 and Duffy. Techniques for biophysical analysis will include mass spectrometry to characterize the presence and homogeneity of post-translational modifications, 19F NMR to examine structural homogeneity, and EPR analysis. Our lab is also initiating a concerted effort in the EPR analysis of the chemokine receptor CCR1. Finally, I am interested in studying the two specific receptors for MEC, CCR10 and CCR3, in terms of ligand/receptor interactions using techniques such as NOE experiments to examine distance/contact information. Overall, I am hoping to combine my previous experience in NMR spectroscopy of small molecules with these new techniques in order to gain a thorough knowledge of the structure and function of these complex chemokine/receptor systems.  
     
  Jeffrey Kearns

jkearns@chem.ucsd.edu
Department:  Chemistry & Biochemistry
Advisor:  Alex Hoffman
Year:  3

 
 

The NFkB family of transcription factors is comprised of dimeric associations of five NFkB protein monomers. These dimers are held in a latent form in the cytoplasm by IkB inhibitor proteins and translocate to the nucleus upon inducible degradation of the IkBs.  Each NFkB dimer activates overlapping but distinct gene expression programs that include the genes for NFkB monomers and IkB inhibitors.  Complexity in this signaling network arises from the temporal, stimulus, and cell-type specific activation of individual dimers as well as both negative and positive feedback mechanisms.  My research project involves tightly integrated computational and biochemical studies to explore network complexity and the mechanisms through which stimuli elicit specific network responses.  Three projects I am currently exploring include the interplays between cellular localization and inducible IkB degradation, negative feedbacks provided by individual IkBs, and positive feedbacks provided by inducible NFkB monomers.  

  • Kearns, J. D., S. Basak, et al. (2006). "IkBe provides negative feedback to control NFkB oscillations, signaling dynamics, and inflammatory gene expression." J. Cell Biol. 173(5): 659-664

 
     
  Andrew Markley

markley@ucsd.edu
Department:  Chemistry & Biochemistry
Advisor:  Jack Dixon
Year:  3
 

 
  Almost every species of bacteria use some form of antimicrobial defense to establish a niche in their respective environments.  Working with colleagues in the Dixon, Nizet, and Dorrestein labs, I have discovered a new, widely distributed class of antibiotic biosynthetic gene clusters.  We have determined that enzymes within these operons post-translationally modify small, ribosomally encoded prepropeptides into antimicrobially active molecules.  It is my goal to characterize the enzymatic activity of these biosynthetic enzymes and determine the final structure of the antibiotic peptides.
 
 
     
  Anna-Clare Milazzo

amilazzo@physics.ucsd.edu
Department:  Physics
Advisor:  Xuong
Year:  5

 
     
     
  Jeff Noel

jknoel@ucsd.edu
Department:  Physics
Advisor:  Jose Onuchic
Year:  2

 
  Coarse-grained structure-based models of protein folding have been shown to correctly reproduce folding mechanisms.  These models allow for a tremendous amount of sampling.  I am working on developing a structure-based model that includes a closer approximation to the real protein geometry by including all the heavy atoms, as opposed to only having beads at the positions of alpha-carbons.  I will use this model to investigate the role side-chain packing plays in folding and the oligomerization of proteins.   
     
  Andro Rios

acrios@ucsd.edu
Department:  Chemistry & Biochemistry
Advisor:  Yitzhak Tor
Year:  2

 
 

The structural diversity and catalytic ability of RNA continues to inspire and motivate scientists to obtain a better understanding of this molecule.  With a desire to be part of this intriguing field of study, I am designing and synthesizing fluorescent nucleosides that closely resemble the natural RNA nucleosides in terms of size, shape and hydrogen-bonding capabilities.   With these newly developed fluorescent nucleosides I can exploit their photophysical characteristics to serve as probes for my studies relating to RNA tertiary structure and for specific mechanistic investigations involving ribozymes.

 
     
  Eric Salgado

esalgado@chem.ucsd.edu
Department:  Chemistry & Biochemistry
Advisor:  A. Tezcan
Year:  2

 
  Metal coordination is an essential structural element in many systems, such as the zinc-finger proteins and calcium-binding EF hand motifs. In many instances, metals are also central to mediating protein-protein interactions, as observed during cellular metal transport. My research is aimed towards the goal of designing and constructing novel metal-binding motifs on protein surfaces that will serve to guide protein-protein interactions under the control of metal coordination. By rationally designing protein-protein interfaces that can be controlled as such, one could potentially gain the ability to manipulate cellular processes while, at the same time, forming functional protein complexes and crystal lattices.  
     
  Diana Schlamadinger

dschlama@chem.ucsd.edu
Department:  Chemistry & Biochemistry
Advisor:  J. Kim
Year:  2
 

 
  Integral membrane proteins are believed to comprise ~30% of all cell proteins, and serve essential roles in cellular function as gates, pumps, receptors, energy transducers, and enzymes. We primarily use UV Resonance Raman Spectroscopy (UVRR) to probe structure and dynamics associated with folding, misfolding, and insertion of integral membrane proteins. Specifically, we are studying a beta barrel membrane protein, outer membrane protein A (OmpA). Goals of this project include measuring the UVRR spectra of both the folded and unfolded states of OmpA, determining the vibrational changes as folding proceeds, and acquiring UVRR spectra of intermediate adsorbed states. The general goal of this project is to help elucidate the folding mechanism of OmpA.  
     
  Yan Wang

yaw004@ucsd.edu
Department:  Chemistry & Biochemistry
Advisor:  S. Opella
Year:  2

 
  The focus of my current research is to determine the structure of virus protein "u" (Vpu) from HIV-1 and its interaction with the CD-4 receptor using both solution- and solid-state NMR techniques.  
     
  Paul Whitford

pwhitfor@physics.ucsd.edu
Department:  Physics
Advisor:  J. Onuchic
Year:  4

 
  I am developing simplified models to describe allosteric conformational changes in proteins.  Using these models I am studying the relationship between protein structure and protein function and am exploring the energetic landscapes of conformational changes.  
     
  Amy Davenport

adavenpo@ucsd.edu
Department: Chemistry & Biochemistry
Advisor:  E. Komives
Year:  2

 
 

The repeating, almost slinky-like, structure of IκBα; allows for interesting studies of the dynamical properties, most of which have been bulk/ensemble average experiments that have given much insight into the folding and binding actions. However, these studies tell us little about what a single protein is doing at any given time. To study this, I will be using an optical method, FRET, as a sort of molecular ruler to look at single molecule dynamics. I hope to bridge computer-based molecular dynamics simulations with my bench work to come out with a more complete picture of what  IκBα; does as a "kicking and screaming stochastic model" in real time.

 
     
  Cathrina Salanga

csalanga@ucsd.edu
Department:  Chemistry & Biochemistry
Advisor:  T. Handel
Year:  4

   
  Chemokines are involved in leukocyte migration associated with routine immune surveillance, as well as induced migration in response to events such as injury or infection; however, inappropriate expression or utilization of chemokines and their receptors has been shown to result in numerous inflammatory diseases. Therefore my research aims to elucidate the molecular mechanisms of chemokine:receptor binding and receptor activation.  Currently, I am using H/D exchange with Mass Spectrometry to identify the respective binding epitopes on a chemokine receptor and ligand, though the results may also reveal dynamic and conformational changes associated with activation or antagonism of the chemokine receptor.  Information gleaned from these studies will guide more directed studies of the receptor-ligand interactions and complement other ongoing studies chemokine receptor-ligand interactions in the Handel lab.  
     
  Carla Cervantes

Department:  Chemistry & Biochemistry
Advisor:  E. Komives
Year:  5