With this award, the Macromolecular, Supramolecular and Nanochemistry Program in the Division of Chemistry is funding Dr. Bradley L. Nilsson from University of Rochester and Dr. Cristiano Dias from New Jersey Institute of Technology to study the structure and molecular driving forces promoting the assembly of beta-sheet peptides. Peptides are naturally occurring biological molecules that are found in all living organisms. In cells, they perform many biological functions, for example acting as hormones. Beta-sheets are a common structure found in peptide assemblies associated with many human diseases, most notable of which is Alzheimer's disease. In this work, co-assembly of two peptides that are mirror images of one another is studied using complementary experimental and computational techniques. These efforts may provide critical insight into the molecular-scale interactions that dictate the assembly of both natural and artificial beta-sheets. The this research could simplify and guide efforts to rationally design and synthesize the next generation of nanomaterials with peptides that are precisely organized. Outreach activities associated with this work includes an inquiry based mini-course on hydrogels called "To Gel or Not To Gel: The Science of Slime" which is conducted at both institutions. Additionally, the two research teams host high school interns for six weeks during the summer to provide mentoring and increase interest in scientific research and chemical sciences in general. This work may provide significant societal benefits because it has the potential to provide insight into disease mechanisms that involve beta-sheet self-assembly, such as in Alzheimer's disease and amyloidosis in general.

This research focuses on obtaining fundamental understanding of the structure and molecular forces driving the co-assembly of L- and D-peptides sequences into rippled beta-sheet nanofibrils. This enables the rational design of new peptide sequences that can form rippled beta-sheet nanofibril systems. In the first objective, complementary experimental and theoretical methods are used to characterize the comparative structures of pleated beta-sheet and rippled beta-sheet nanofibrils. The second objective exploits theory in the computationally-directed assessment and design of rippled beta-sheet nanofibrils from L- and D-peptide sequences. The knowledge obtained may be applicable not only to these specific materials, but also to understanding the role of beta-sheet structures in amyloid self-assembly and in protein folding in general. This work may provide significant societal benefits because it has the potential to provide insight into disease mechanisms that involve beta-sheet self-assembly, such as in Alzheimer's disease and amyloidosis in general.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

Agency
National Science Foundation (NSF)
Institute
Division of Chemistry (CHE)
Type
Standard Grant (Standard)
Application #
1904528
Program Officer
Tomislav Pintauer
Project Start
Project End
Budget Start
2019-09-01
Budget End
2022-08-31
Support Year
Fiscal Year
2019
Total Cost
$392,506
Indirect Cost
Name
University of Rochester
Department
Type
DUNS #
City
Rochester
State
NY
Country
United States
Zip Code
14627