Current Cluster Students

Olivia Barber

 

Olivia Barber
Grad Program: Environmental Engineering
Ph.D. Advisor: Erica Hartmann

Doctoral Research Project:  
Antimicrobial resistance (AMR) is a rising concern that threatens to undermine modern medical practices and antibiotics. The human contribution to AMR remains poorly understood and practical strategies to stem the rise of resistance are even less defined. My work in the Hartmann lab examines how our disinfection regimes and widespread use of antibiotics impacts antibiotic resistance in the built environment. I am interested in quantifying the human impact on AMR and how it impacts health outcomes. My work also focuses on how proposed solutions to AMR, such as bacteriophage therapy, can reverse the current trend of resistance and allow continued use of antimicrobials in specific, critical circumstances. 

 

Sofia Gonzalez Schuler

 

Sofia Gonzalez Schuler
Grad Program: ChBE
Ph.D. Advisor: Milan Mrksich

Doctoral Research Project:  
One of the molecular candidates responsible for neuronal damage seen in Alzheimer’s Disease (AD) is the peptide amyloid-beta. Amyloid-beta aggregates into oligomers (ABOs) and fibrils in brain tissue. Evidence discovered by the Klein laboratory at Northwestern suggests that these ABOs bind to neuronal cell surfaces where they induce synaptic degradation, oxidative stress, and cell death. A leading hypothesis is that ABOs – and not smaller units such as monomers or dimers, or larger aggregates that form fibrils – are responsible for the adverse neural effects that produce AD. This has led our collaborators, the Klein laboratory, to develop antibodies capable of selectively binding to ABOs of various sizes and conformations for use in research, diagnostics, and therapeutics. Specifically, the Klein group has developed several single-chain variable fragments (scFvs) and monoclonal IgGs with selectivity for ABOs. As evidence continues to mount showing the importance of the specific forms of AB aggregation, I can expect that the form of therapeutic candidates will also be of significance as these candidates attempt to selectively bind to and neutralize the ABO toxicity. However, modifications to the form of antibodies typically fall within a relatively confined design space and continue to pose significant technical challenges. The Mrksich laboratory has developed a modular platform, called the megamolecule strategy, to synthesize multi-protein assemblies by covalently joining protein domains to with both precision and efficiency – overcoming the constraints of synthesizing typical antibody scaffolds. These molecules are made by fusing enzymes or antibody fragments with a connection protein domain, where a nucleophilic residue in the active site of the connecting domain can be irreversibly modified by a targeted covalent inhibitor on a PEG backbone. I propose the use of this platform to generate libraries of anti-ABO megamolecule antibodies varying in size and geometry to (i) identify designs with both greater selectivity and affinity for the appropriate ABO structures and (ii) to enhance our ability to both neutralize and disrupt ABO formation pathophysiology.

 

Taylor Gunnels

 

Taylor Gunnels
Grad Program:BME
Ph.D. Advisor: Neha Kamat & Josh Leonard

Doctoral Research Project:  The ability to engineer biological cells to perform custom sense-and-respond functions has wide-ranging applications including environmental monitoring, diagnostics, and therapeutic delivery. Unfortunately, cellular biosensing systems may be subject to genetic drift or instability that impairs their performance and may pose biocontainment risks if they are released into the environment. I aim to overcome these challenges by functionalizing amphiphilic vesicles with engineered protein receptors to generate a vesicle-based biosensing system. By leveraging membrane and protein engineering strategies from the Kamat and Leonard Labs, I then hope to utilize this biosensing system for use as in vivo diagnostic and therapeutic tools.

 

Ruth Lee

 

Ruth Lee
Grad Program:MSE
Ph.D. Advisor: Samuel Stupp

Doctoral Research Project:  Peptide amphiphiles are biocompatible molecules that self-assemble into nanostructures in water and have been extensively studied for applications in regenerative medicine and tissue engineering. However, current peptide amphiphile systems are static and do not respond to dynamic cues in the microenvironment of cells. Currently I am working on creating stimuli-responsive peptide amphiphile systems using various nanoscale materials characterization techniques. By utilizing different types of external stimuli, we can control the stiffness and viscoelasticity of the resulting material to mimic the extracellular matrix of the cell. My ultimate goal for this project is to develop biocompatible, biomimetic robotic soft matter for biomedical applications and to study the cell-material interactions at various length scales. 

 

Roxi Mitrut

 

Roxi Mitrut
Grad Program: ChBE
Ph.D. Advisor: Josh Leonard

Doctoral Research Project:  Extracellular vesicles (EVs) can be engineered to have novel functions, including targeting EVs to specific cell types and directing loading of specific biomolecular cargo molecules, and have broad therapeutic potential. However, they can be costly and challenging to produce on clinically-relevant scales. In order to further expand the potential for these therapies, my research is currently focused on creating an implantable device capable of sustained, local production and delivery of a bioactive engineered EV therapeutic in situ. Isolation of the engineered cells from their environment by embedding them within a hydrogel matrix should also shield the implanted cells from surrounding host cells and the immune system.