Metabolic exchange is a universal phenomenon. It is essential to every organism, from those as simple as bacteria to complex higher eukaryotes such as humans. While metabolic exchange enables cooperation and coordination between the ~70 trillion cells in an average human being, even unicellular organisms rely on metabolic exchange to adapt to environmental stress and form biofilms. Cellular communication allows stem cells to differentiate, cancer cells to proliferate, neurons to fire, bacteria to sense a quorum and pathogens to survive in human hosts. The chemical diversity of the molecules used for communication is extraordinary, and includes small ions such as calcium, small molecules such as secondary metabolites, fatty acids, peptides, but also carbohydrates, proteins and nucleic acids. Despite the universal nature of metabolic exchange, there are few methods that can characterize the communication between cells in a systematic and sensitive fashion, let alone real-time. In this proposal, our focus will be on the application and adaptation of desorption electrospray mass spectrometry to enable the real-time live cell detection and the characterization and visualization of metabolic exchange in important biological processes.
We aim to accomplish this in both a spatial as well as temporal fashion. These tools will improve our understanding of secreted biomarkers, microbiome-human cell interactions and understanding the complexities of infectious disease that derive from the cooperation between different types of cells (e.g. Bacilli with macrophages, neutrophils or T-cells) and interkingdom communication. Ultimately it may drive the development of new therapeutic strategies or interventions based on paradigms involving inter-cellular metabolic communication in a system wide fashion.

Public Health Relevance

This proposal aims to develop real-time monitoring of molecular entities involved in metabolic exchange of pathogen-immunological cell populations. Our ability to "visualize" metabolic exchange between different cell populations could lead to new therapeutic paradigms.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM094802-03
Application #
8331499
Study Section
Special Emphasis Panel (ZGM1-GDB-7 (EU))
Program Officer
Edmonds, Charles G
Project Start
2010-09-01
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
3
Fiscal Year
2012
Total Cost
$255,072
Indirect Cost
$81,822
Name
University of California San Diego
Department
None
Type
Schools of Pharmacy
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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