Heterotrimeric G proteins are important bi-molecular switches that transmit signals from a diverse array of membrane receptors for neurotransmitters, hormones and extracellular morphogens to activate downstream intracellular signaling pathways. Members of the G?12/13 family are particularly important during embryonic development as they are essential for the development of the circulatory system and are required for embryonic angiogenesis. The goal of this proposal is to understand how Ric-8 participates in signaling in the G?12/13 pathway. We will use the Drosophila gastrulation pathway as a model system to study Ric-8 to take advantage of the powerful cell biological tools and rich understanding of the G?12/13 signaling pathway in flies. In this proposal we will 1) Conduct a structure-function study of Ric-8 within the context of G?12/13 signaling;and 2) Identify novel proteins that are required for regulating Ric-8 activity in Drosophila. Given the hih degree of conservation of these pathways between flies and humans, these studies will provide understanding of the regulation of G?12/13 protein signaling during vascular development and will identify novel molecules with potential therapeutic importance in the regulation of angiogenesis.

Public Health Relevance

The proposed research is relevant to public health as it will advance our understanding of the signaling pathways involved in development of the circulatory system. These pathway play a key role in angiogenesis and understanding them at molecular detail will allow development of novel therapies that promote formation of blood vessels after injury or block angiogenesis during the tumorigenesis.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
1R03HD077523-01
Application #
8568833
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Mukhopadhyay, Mahua
Project Start
2013-08-02
Project End
2015-07-31
Budget Start
2013-08-02
Budget End
2014-07-31
Support Year
1
Fiscal Year
2013
Total Cost
$76,000
Indirect Cost
$26,000
Name
University of North Carolina Chapel Hill
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Manning, Alyssa J; Rogers, Stephen L (2014) The Fog signaling pathway: insights into signaling in morphogenesis. Dev Biol 394:6-14