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Principal Investigator: Wheeler, Korin Evelyn
Institute Receiving Award Santa Clara University
Location Santa Clara, CA
Grant Number R15ES025929
Funding Organization National Institute of Environmental Health Sciences
Award Funding Period 01 Sep 2016 to 31 Mar 2021
DESCRIPTION (provided by applicant):  DESCRIPTION: Despite the innovations in nanotechnology in the past few decades, biological fate and toxicity of engineered nanomaterials (ENMs) is poorly understood with respect to molecular level interactions with biological systems. In living systems, ENMs undergo chemical and physical changes, including adsorption of biological macromolecules like proteins. This "protein corona" leaves the particle surface with little resemblance to the original ENM, altering the bioavailability, reactivity, and biological response. The central hypothesis of this project is that peptides can serve as structural mimics of physiologically relevant proteins to probe physiochemical characteristics mediating ENM protein corona formation, dynamics and biological response. The biophysical attributes of ENMs and proteins that facilitate interaction will be discovered by studying a library of structurally diverse peptides upon interaction with a small collection of noble metal ENMs, varied in material and surface chemistries. The proposed experiments provide novel probes of molecular level protein-ENM reactivity that span various levels of complexity. The specific aims of the research are: (1) evaluate biophysical characteristics that facilitate protein-ENM interactions and stability, (2) to characterize individal peptides dynamics within a complex, dynamic ENM protein corona, and (3) to assay the role of the changing protein corona in mammalian cell response to ENMs. The tools developed will be broadly applicable to the major challenge of characterizing coronal protein dynamics within complex systems. Long term implications of this work include prioritization of engineered and biological properties that mediate ENM physiological reactivity, with applications in ENM design and safe use in nanomedicine.
Science Code(s)/Area of Science(s) Primary: 78 - Nanotoxicology
Publications See publications associated with this Grant.
Program Officer Srikanth Nadadur
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