Orchestrated membrane remodeling creates flows of substance and information to sustain the lifecycle of a cell. Therefore understanding the molecular mechanisms that cells use to generate, maintain and deform the membrane structures has been a central task of cell biology. Cell-free experiments provide a clean system to study the functional interactions between the biomolecules that mediate the cell membrane remodeling. However, most of previous in vitro studies lack the precise control of the physical and chemical properties of the membrane (e.g. membrane vesicle's size and shape;local density and spatial organization of membrane- associating proteins), thus leaving considerable room of ambiguity. We hypothesize that we could engineer membrane remodeling events with a high level of control and further elucidate the molecular mechanisms for cell membrane dynamics by setting up in vitro scenarios in which the membrane modulating elements are precisely organized on DNA nanostructures. In other words, we plan to dissect the membrane trafficking machineries by artificially placing their natural components on a programmable nano-template. We propose to use this transformative approach to study the underlying mechanism of SNARE mediated membrane fusion as well as the membrane curvature sensing/inducing activities of BAR-domain proteins. Beyond the goals set by this proposal, we believe our project could open doors for new therapeutic strategies for membrane trafficking related diseases as well as efficient drug-delivery nanomachines.

Public Health Relevance

We propose to dissect membrane trafficking via cell-free experiments where the vesicle geometry, protein density/arrangement and membrane remodeling kinetics are controlled by programmable nano-templates made of DNA. The proposed research could open doors to new therapeutic strategies for membrane trafficking related diseases as well as efficient drug-delivery nanomachines.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
NIH Director’s New Innovator Awards (DP2)
Project #
1DP2GM114830-01
Application #
8756039
Study Section
Special Emphasis Panel (ZRG1-MOSS-C (56))
Program Officer
Chin, Jean
Project Start
2014-09-30
Project End
2019-06-30
Budget Start
2014-09-30
Budget End
2019-06-30
Support Year
1
Fiscal Year
2014
Total Cost
$2,497,500
Indirect Cost
$997,500
Name
Yale University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06510