Nutritional status affects many aspects of physiology, including reproduction and cell proliferation. It is increasingly important to understand the effects of nutrition on cell behavior at the molecular level, since devastating diseases such as diabetes are linked to improper cellular responses to nutritional input. The proposed research will further the understanding of the connection between molecular pathways that respond to nutritional control and cell proliferation. Our studies will provide a deeper understanding of the relationships between nutritionally linked diseases such as diabetes and cell-proliferation diseases such as cancer, which occurs at a higher incidence in diabetic patients. The molecular mechanisms by which nutrition-sensitive molecular pathways control reproduction and cell proliferation are not well understood. The nematode C. elegans is an excellent model organism for studying the cellular effects of conserved nutritionally-responsive signaling pathways such as the insulin signaling pathway on germline cell proliferation in the context of a whole organism. Our recent results implicate the insulin pathway in germline proliferation in C. elegans, with specific effects on germline cell cycle. I am currently investigating the TOR-S6K pathway, another key nutrition-sensitive pathway that is thought to act in concert with the insulin signaling. My work addresses the following questions: What role does the TOR-S6K pathway play in germline proliferation? What is the connection to the insulin pathway? What are the downstream effectors of S6K for the germline phenotype?

Public Health Relevance

Project Narrative Our long-term goal is to understand how nutritional status affects cell proliferation. Molecular pathways that respond to nutrition and that control cell cycle are conserved in all organisms. We are using a simple experimental system, the germ line of C. elegans as a model to investigate the connection between these fundamental processes that affect normal physiology and development as well as disease states.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30DK089697-03
Application #
8318250
Study Section
Special Emphasis Panel (ZDK1-GRB-W (O1))
Program Officer
Castle, Arthur
Project Start
2010-09-28
Project End
2013-09-27
Budget Start
2012-09-28
Budget End
2013-09-27
Support Year
3
Fiscal Year
2012
Total Cost
$38,832
Indirect Cost
Name
New York University
Department
Pathology
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Hubbard, E Jane Albert; Korta, Dorota Z; Dalfรณ, Diana (2013) Physiological control of germline development. Adv Exp Med Biol 757:101-31
Korta, Dorota Z; Tuck, Simon; Hubbard, E Jane Albert (2012) S6K links cell fate, cell cycle and nutrient response in C. elegans germline stem/progenitor cells. Development 139:859-70