Current Trainees

Abigail Miller

Email: abm006@ucsd.edu
Undergrad Institution: Boston College
Current Program at UC San Diego: Biochemistry and Molecular Biophysics
Advisor: Tatiana Mishanina

Targeting Riboswitch Folding Intermediates in Acinetobacter baumannii Using Antisense Oligonucleotides as Novel Antibiotics

Bacterial riboswitches are regulatory RNAs that bind specific ligands and undergo a conformational change to serve as a control mechanism of gene expression. Upon ligand binding, downregulatory riboswitches can act at either the transcriptional level by promoting premature transcript termination or at the translational level by sequestering the ribosome binding site. Thiamine pyrophosphate (TPP) riboswitches are key regulators of thiamine biosynthesis in many organisms. While significant research has been completed on the E. coli thiC TPP riboswitch, the thiC riboswitch in the multidrug resistant pathogen, Acinetobacter baumannii, differs in sequence and, therefore, potentially differs in regulatory mechanisms. I aim to characterize the structure and regulatory mechanism of the A. baumannii thiC riboswitch (Ab01), both in vivo and in vitro and to map the co-transcriptional folding pathway of the riboswitch at single nucleotide resolution. Characterizing the A. baumannii thiC riboswitch and mapping the RNA folding pathway will ultimately enable me to identify targets for antisense oligonucleotides that can bind to the riboswitch of interest and alter gene regulation, serving as an antibiotic.

Adele Nguyen

Email: adn022@ucsd.edu
Undergrad Institution: University of California, Los Angeles
Current Program at UC San Diego: Biochemistry and Molecular Biophysics
Advisor: Alexandra Newton

Uncovering the Conformational States of Wildtype and Mutant PKCγ Throughout its Life Cycle via Hydrogen-Deuterium Mass Spectrometry

My research addresses the major challenge of understanding the complex conformational transitions that regulate the function of protein kinase C gamma (PKCγ), a key signaling enzyme whose aberrant function drives Spinocerebellar Ataxia Type 14. I will be utilizing biophysical characterization, primarily via hydrogen-deuterium exchange mass spectrometry (HDX-MS), to complement structural studies to reveal the conformational states of PKCγ in its native and disease-related forms.

Annie Charvat

Email: acharvat@ucsd.edu
Undergrad Institution: University of San Francisco
Current Program at UC San Diego: Biochemistry and Molecular Biophysics
Advisor: Jin Zhang

Mechanisms and Functional Consequences of RIβ Condensates in Neurons

Biomolecular condensates organize cellular signaling pathways, and defects in these structures are increasingly linked to neurodegenerative disease. In the Zhang lab, I use human induced pluripotent stem cell (iPSC)-derived neurons to investigate how the neurodegeneration-associated RIβL50R mutation alters condensate material properties and cAMP/PKA signaling dynamics compared to wild-type RIβ. By integrating live-cell biophysical approaches with functional signaling measurements, my work aims to reveal how disrupted condensate organization contributes to neuronal dysfunction and disease.

Daniel Mansour

Biophysical Modeling of Actin Networks Regulated by Liquid-like Protein Droplets

Several actin-binding proteins form liquid-liquid phase-separated condensates that promote actin filament assembly and bundling, which is crucial for local actin network organization. I am developing quantitative, predictive computational models that capture how actin filaments interact with these phase-separated condensates to form different actin networks. My research investigates how the interplay between physical properties and biochemical composition of condensates drives actin network organization and force generation.

Devlin Swanson

De novo design of multi-conformational proteins

Proteins derive their function through control of their energy landscape. While the ability to design proteins has improved dramatically in recent years, current methods struggle to design in the context of thermodynamics. I aim to improve on this by designing proteins that can adopt multiple conformations, and tune the energetics between multiple states. To achieve this, I will combine computational deep-learning techniques with experimental validation through cryo-electron microscopy (cryoEM).

Emma Cushman

Email: ecushman@ucsd.edu
Undergrad Institution: University of Wisconsin-Madison
Current Program at UC San Diego: Biochemistry and Molecular Biophysics
Advisor: Alex Guseman

Elucidating the Sequence Grammar of Oscillatoria agardhii Agglutinin for Bioanalytical Tools

My project’s main goal is to define and manipulate the sequence features that govern multivalency across lectins, specifically Oscillatoria agardhii agglutinin (OAA), to enhance therapeutic or bioanalytical properties. Combining alanine scanning and saturation mutagenesis will map key glycan-binding residues and their physicochemical properties, establishing a design framework for engineering enhanced affinity and selectivity toward cancer-associated glycan signatures.

Jasmine Wiese

Email: jawiese@ucsd.edu
Undergrad Institution: Carnegie Mellon University
Current Program at UC San Diego: Biochemistry and Molecular Biophysics
Advisor: Christopher Lee

The role of membrane phase separation in regulating plasma membrane rupture

NINJ1 mediates plasma membrane rupture during lytic cell death. Since NINJ1 is constitutively present in the membrane, its control must be tightly regulated. I hypothesize that lipid phase separation is the trigger for NINJ1 activity, motivated by evidence that NINJ1 localizes to the phase separation boundary and that NINJ1-mediated punctures match the scale of lipid rafts. Using molecular simulations, I aim to elucidate how lipids in the plasma membrane shape NINJ1 behavior and function.

Julissa Cruz Bautista

Email: jcruzbautista@ucsd.edu
Undergrad Institution: Wesleyan University
Current Program at UC San Diego: Biochemistry and Molecular Biophysics
Advisor: Christopher Obara

Membrane-anchored innate immune signaling: single-molecule analysis of the cGAS-STING and RIG-I/MAVS pathways on cellular organelles

The innate immune pathways cGAS-STING and RIG-I/MAVS are activated on organelle membranes, yet how their spatial organization regulates signaling remains poorly understood. My research uses live-cell single-molecule microscopy to investigate how these pathways reorganize during activation. By tracking individual STING molecules in living cells, I examine how activation influences their mobility and localization within the endoplasmic reticulum. Ongoing work extends this approach to MAVS and ER-mitochondria contact sites to determine whether these pathways share common spatial mechanisms that coordinate and amplify the cellular antiviral response.

Megan Judson

Email: mejudson@ucsd.edu
Undergrad Institution: Ohio State University
Current Program at UC San Diego: Biochemistry and Molecular Biophysics
Advisor: Galia Debelouchina

Biophysical Characterization of the Regulation of Lamin B Receptor’s Dual Functions

The lamin B receptor (LBR) is a nuclear membrane protein that tethers heterochromatin to the nuclear lamina and acts as a sterol reductase in the cholesterol synthesis pathway. While these roles have been studied independently, their relationship is poorly understood. My research will characterize the role of phosphorylation in regulating LBR’s interactions with chromatin and explore how the structural and enzymatic activities of LBR may be functionally linked.

Olivia Seidel

Uncovering the rules of lipid transport at membrane contact sites with new lipid flux sensors and single molecule tracking

Cells actively maintain the unique identity of organelles through targeted lipid trafficking and synthesis. Yet, the mechanisms by which it does these are largely unknown due to current limitations that come with imaging lipids, which include their relatively small size and their sensitivity to tagging-induced perturbations. To overcome these limitations, I am working on combining two imaging techniques developed by the Budin and Obara labs: Fluorogen-Activated Coincidence Sensing (FACES) and high-speed Single Molecule Tracking (SMT) to visualize lipids in a living cell in a spatially localized manner. I hypothesize that functional cell homeostasis and organelle membrane identity are generated by nanoscale, spatially regulated lipid trafficking and synthesis events. To target this hypothesis, I will be working to characterize the motion of individual lipid molecules in living cells, visualize lipid transfer events as they occur in their native membranes, and identify the rules that govern lipid transport at membrane contact sites.

Sarah Johnson

Designing Multi-Targeting Protein Binders to Combat Antibiotic Resistance

Antimicrobial resistance is a global health threat and a growing barrier to the treatment of Mycobacterium tuberculosis (M.tb), the deadliest human pathogen. I seek to engineer a multi-targeting protein therapeutic to treat drug-resistant tuberculosis. By targeting various fitness and resistance mechanisms simultaneously, I intend to reduce the capacity of M.tb to survive and escape antibiotic effects. MmpLs are a family of transporters in M.tb that are critical for bacterial survival and virulence. I am employing machine learning-based methods to design de novo inhibitors of mmpLs, combined with high-throughput experimental assays to evaluate protein binding and microbial fitness.

Stephanie Ouderkirk

Email: souderkirk@ucsd.edu
Undergrad Institution: James Madison University
Current Program at UC San Diego: Biochemistry and Molecular Biophysics
Advisor: Kevin Corbett

Structural and Functional Characterization of Novel Bacterial Defense Systems: Uncovering New Principles of Immunity

Over billions of years, bacteria have evolved a multitude of immune pathways that protect them from constant attacks from viruses (phages) in their environment, and recent work on these pathways has driven the development of revolutionary biotechnology tools and provided new insight into the human immune system. My project aims to uncover the mechanisms of a group of newly identified immune pathways that share a common sensor domain coupled to diverse effectors, thereby revealing new principles of the bacterial immune system.