CAREER: Understanding the Structure-Interaction-Reactivity Relationship between Small Molecules and Metal-Amyloid Species

Regents Of The University Of Michigan - Ann Arbor, Ann Arbor MI

Investigators

Abstract

With this CAREER Award the Chemistry of Life Processes program is supporting Professor Mi Hee Lim at the University of Michigan to design and synthesize chemical libraries to establish a relationship between structures and interactions with metal-associated amyloid-beta species. In this research program Professor Lim and her students will determine the structural moieties and scaffolds required for interactions with metal ions, amyloid-beta, and metal-amyloid-beta species. The research group will synthesize multiple chemical series via systematic structural modifications of small molecules previously demonstrated to interact and react with amyloid-beta or metal-amyloid-beta species. The interactions of newly prepared molecules with metal ions, amyloid-beta, and metal-amyloid-beta species will be characterized to full chemical resolution using appropriate analytic methods, such as UV-Visible and NMR spectroscopy, mass spectrometry (MS), and X-ray crystallography. The results of this research effort will provide insight into the development of chemical tools suitable for investigating the involvement of metal-amyloid-beta species in neurotoxicity leading to neurodegeneration. Since it is not well understood how the interactions of metal ions with amyloid-beta species could be associated with neurotoxicity, it is necessary to have appropriate chemical tools that can simultaneously target metal-amyloid-beta species and modulate their interactions. In pursuing this research program, the Lim group will provide opportunities for students from high school through graduate student level to conduct interdisciplinary research in bioinorganic chemistry. Students with diverse backgrounds who traditionally have not studied this field will not only be taught the concepts of bioinorganic chemistry, but also will be introduced to exciting chemistry research in the laboratory. Professor Lim will also create professional development opportunities for female scientists (undergraduate to postdoctoral), with special attention to outreach to local companies, dialogue among different levels of female chemists, and continuous communication. Through these efforts, future female scientists will be encouraged to enhance their involvement in the sciences and pursue their career goals.