Do intracellular temperature gradients regulate cellular functions? It is fundamental to our understanding of biochemistry that enzymatic reactions are temperature-dependent, yet we tend to presume that intracellular temperature gradients, if they occur at all, must be dissipated so quickly as to be inconsequential. We hypothesize that intracellular temperature gradients may be as significant as ion gradients (e.g. Ca++ or pH) in regulating cellular functions. The challenge in addressing this question is to establish methodology for measuring meaningful changes in temperature at the subcellular level and to identify a biological process in which the role of this hypothesized temperature regulation can readily be assessed. We are developing methodology for measuring subcellular temperature changes in macrophages and applying these measurements to the process of phagocytosis, a process that strongly activates the cells and one in which degradative enzymes are enlisted to kill potentially threatening microbes. Preliminary data presented demonstrate that significant "Phagosomal Heating" occurs. The project is innovative in that intracellular temperature variations have not yet been implicated as important for regulating cellular functions. With this project, we intend to add a novel method of signaling to our understanding of molecular and cellular biology regulatory mechanisms. The approaches developed will be applicable to all areas molecular and cellular biology.

Public Health Relevance

Phagocytosis is the process by which white blood cells eat and kill foreign microbes. Upon internalizing microbes into intracellular compartments called phagosomes, these white blood cells use a variety of mechanisms to them including surrounding them with digestive enzymes, acidifying their environment, and bathing them in highly caustic reactive oxygen radicals. In this project, we hypothesize that all of these approaches are aided and enhanced through active Phagosomal Heating whereby the temperature of the intracellular compartment containing a microbe is raised much higher than previously thought possible.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI103471-01A1
Application #
8698868
Study Section
Innate Immunity and Inflammation Study Section (III)
Program Officer
Palker, Thomas J
Project Start
2014-02-01
Project End
2016-01-31
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
1
Fiscal Year
2014
Total Cost
$192,285
Indirect Cost
$57,285
Name
Cedars-Sinai Medical Center
Department
Type
DUNS #
075307785
City
Los Angeles
State
CA
Country
United States
Zip Code
90048