With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Arne Gericke and Dr. Qi Wen from Worcester Polytechnic Institute to identify the physicochemical conditions that lead to the clustering of phosphoinositide lipids in complex lipid mixtures and to characterize the membrane association of the phosphatase PTEN with such laterally heterogeneous lipid bilayers. Lipids are major building blocks of cellular membranes and a subclass of these biomolecules control cellular functions by attracting proteins to distinct cellular sites at specific times. Such lipid mediated signaling events require a high degree of organization in space and time, and deviations from the proper execution of these signaling pathways result in a wide array of cellular dysfunctions. The cellular requirements for the local accumulation of signaling lipids are only beginning to emerge and the mechanisms leading to the time dependent control of these lipid pools need to be determined. The research funded under this proposal will delineate the mechanisms that lead to the formation and maintenance of localized pools and gradients of signaling lipids. Graduate and undergraduate students will receive training in many modern research techniques, including single molecule microscopy. The principal investigator will continue to develop inquiry based middle school science projects and his research group will be involved in a range of STEM outreach activities.

The impact of the research will be to understand how phosphoinositides, which are minority components of plasma and intracellular membranes, provide spatiotemporal control of protein function. Phosphoinositide gradients have been observed in vivo, however, currently there is no experimental platform available that enables the testing of hypotheses about how these gradients are created and maintained. This grant supports the development of a microfluidic device that will be used to systematically investigate how phosphoinositide gradients are created through the action of phosphoinositide specific kinases and phosphatases and subsequently stabilized by other biomolecules.

Agency
National Science Foundation (NSF)
Institute
Division of Chemistry (CHE)
Application #
1508499
Program Officer
Catalina Achim
Project Start
Project End
Budget Start
2015-06-01
Budget End
2019-05-31
Support Year
Fiscal Year
2015
Total Cost
$480,000
Indirect Cost
Name
Worcester Polytechnic Institute
Department
Type
DUNS #
City
Worcester
State
MA
Country
United States
Zip Code
01609