Co-hosted by Georgia Tech's Institute for Bioengineering and Bioscience and the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. 

"Designing Molecular Discovery Tools"

Handan Acar
Assistant Professor
Stephenson School of Biomedical Engineering 
University of Oklahoma

Register HERE to participate via Zoom

ABSTRACT
“First, do no harm”…unless the goal is to elicit an immune response. This talk will explore our innovative approach to engineering peptide-based tools designed to stress cell membranes and trigger immune activation. When cells are under stress, they release damage-associated molecular patterns (DAMPs) to signal potential danger to the immune system. Although DAMPs play a crucial role in immunological responses and therapies, the mechanisms behind their release remain elusive. Developing tools that enhance our understanding and control of DAMP release represents a significant advancement for immunotherapy.

Self-assembling peptide nanomaterials have vast potential in medical applications, yet discovering sequences that form functional nanostructures in biological environments remains challenging. While editing natural protein sequences can aid discovery, the properties and applications of these peptides must be thoroughly characterized. This presentation will highlight our unique approach to defining the intermolecular interactions governing peptide function, focusing on controlled cell stress induction. Our "co-assembly of oppositely charged peptides" (CoOP) framework promotes assembly between two hexapeptides with opposite charges, facilitating a systematic analysis of their assembly kinetics and enabling peptide design for specific biological functions.

We have shown that peptides designed using the CoOP strategy integrate into cell membranes, inducing controlled stress and promoting DAMP release. This mechanism has demonstrated the potential to enhance antibody responses in flu vaccines. By tuning the aggregation kinetics of these peptides, we can modulate the cellular stress and, consequently, the type, rate, and volume of DAMPs released, tailoring immune responses.

Our overall research focus is to create molecular tools for desired functions. To identify global rules for molecular tools, rather than mimicking the amino acid sequences of the natural proteins, we mimic their activity and aggregation in a framework. Even non-functional sequences provide valuable insights, driving forward peptide engineering and materials science by illuminating the critical roles of intermolecular interactions. This knowledge paves the way for innovative tools to improve human health and advance scientific understanding.

References:

1. Hamsici, S.; White, A. D.; Acar, H. Science Advances 2022. DOI: 10.1126/sciadv.abj0305.
2. Gunay, G. et al. Advanced Science 2022. DOI: 10.1002/advs.202105868.
3. Hamsici, S. et al. BioRxiv 2022. DOI: 10.1101/2022.06.02.494564.

BIO
Handan Acar is a Stephenson Assistant Professor at the University of Oklahoma's Stephenson School of Biomedical Engineering. She earned her Ph.D. in Materials Science and Nanotechnology from Bilkent University and completed postdoctoral research at the University of Chicago, collaborating with polymer scientists and clinical physicians to develop peptide-based tools for manipulating immune and cancer cell signaling. Acar's research focuses on engineering peptide-based biomaterials for diverse applications, including cancer immunotherapy, vaccine development, and tissue engineering scaffolds. She is recognized for pioneering work on peptide aggregation's role in immunogenic cell death and designing customizable peptide assemblies for immune modulation.