This award by the Biomaterials program in the Division of Materials Research to University of California Los Angeles aims to leverage recently developed knowledge of electrostatics and hydrophobicity in the context of self assembly in cell membranes. How and why protein-lipid interactions generate molecular scale membrane curvature will be studied with respect to current interest in antimicrobials and apoptosis proteins. The rational design of antimicrobials and the regulation of apoptosis, or programmed cell death would be the potential outcomes of these studies. With respect to antimicrobials, there is an urgent need for effective ones to kill new strains of antibiotic-resistant bacteria. Antimicrobial peptides (AMPs) that kill bacteria occur in a broad range of animals, but their mechanisms of action are not well understood. A new class of AMPs of particular importance to humans called defensins will be studied with this project in developing an understanding how and why defensins kill bacteria by producing pores in their cell membranes but not in mammalian cell membranes. The second part of the project is to study B cell lymphoma 2 (BCL2) proteins, which are responsible for programmed cell death, a process through which unwanted or defective cells are killed by inducing pore formation in mitochondria. This project plans to quantify how BCL2 induces topological changes in the mitochondrial membrane that cause the death of cells. With respect to broader impact, this multi-disciplinary project is expected to provide ample educational opportunities to both graduate and undergraduate students. In addition, the proposed research topics are conducive to training for academic and industrial employment. The project will provide research internships to underrepresented undergraduate students and veterans. There are specific plans for the incorporation of results from this research project into the advanced undergraduate/graduate classes of the investigator. Supplemental enrichment educational modules will be provided to economically disadvantaged students at the local high schools.

This research project aims to leverage recently developed knowledge in physics to understand two related problems, one that impacts infectious diseases, and second one that impacts cancer. The first part of this project would be development of new antimicrobials. There is an urgent need for new antibiotics with the increasing incidences of infections by antibiotic-resistant bacteria. Antimicrobial peptides (AMPs) that have killed bacteria for millions of years occur in a broad range of animals, but their mechanism of actions are not well understood. One objective of this project will be studying a class of antimicrobial peptides of particular importance to humans called defensins. Mechanisms by which these peptides kill bacteria by creating pores in their cell membranes, but not in human cell membranes, will be investigated by this project. The knowledge base developed by these studies would be of benefit in developing new synthetic antimicrobials. The second part of this project will be in studying proteins that are responsible for program cell death. These proteins, B cell lymphoma 2 (BCL2), are responsible for so-called programmed cell death, a process through which unwanted or defective cells are killed. For reasons not well understood, cancer cells do not do this. With this research project, the investigators will examine quantitatively how this programmed cell death is accomplished by these proteins. A successful outcome from these studies could lead to the development of new therapeutic strategies in the treatment of a wide range of cancers. With respect to broader impacts, this multi-disciplinary nature of this project will provide ample educational opportunities to students in providing them training for academic and industrial employment. Specific plans are detailed in the proposal to provide research internships to underrepresented undergraduate and veteran students. In addition, results from this research will be incorporated into the PI's advanced undergraduate/graduate classes. Supplemental educational modules also will be provided to economically disadvantaged students at local high schools.

Agency
National Science Foundation (NSF)
Institute
Division of Materials Research (DMR)
Application #
1106106
Program Officer
Joseph A. Akkara
Project Start
Project End
Budget Start
2011-09-15
Budget End
2014-08-31
Support Year
Fiscal Year
2011
Total Cost
$450,000
Indirect Cost
Name
University of California Los Angeles
Department
Type
DUNS #
City
Los Angeles
State
CA
Country
United States
Zip Code
90095