Lay Summary

Proposal No.   IBD-0090R
Principal Investigator:  Otto Phanstiel, Ph.D.
Applicant Organization:   University of Central Florida (Orlando, U.S.A.)
Project Title:  Development of polyamine conjugates as sensitive probes to explore inflammatory bowel disease processes
Period of Award:  May 1, 2004 – February 28, 2007

The study will develop new methods to study polyamines in inflammatory bowel disease (IBD).  The methods are innovative as they utilize a ubiquitous molecule, i.e., a polyamine, to probe IBD.  While all cells contain polyamines and require them in order to grow, their role in IBD is unknown.  There is a significant amount of preliminary findings that supports the possible role of polyamines in inflammation and in immune response.

This study will examine the role of polyamines (and their transport) in IBD by linking a polyamine to a fluorescent tag that lights up when illuminated with ultraviolet light.  This “lighting-up” or fluorescent feature allows one to follow the polyamine as it journeys into the cell.

The key hypothesis in this study is that high polyamine transport activity plays a causative role in IBD.  One should be able to study this premise by measuring how quickly the polyamine probe enters IBD-afflicted macrophages versus normal samples.  In addition, we will attempt to “fish-out” the polyamine transporter (PAT) protein itself using an affinity column that will separate this protein from other cellular components.  Structural information about the polyamine transporter itself will facilitate new drug design.

Macrophages are important immune cells that eat invaders and are involved in the inflammatory response by the human host.  Their ability to attack invaders is lowered by the presence of high levels of a polyamine, spermidine.  If the polyamine levels and import rates are high for IBD-afflicted tissues and associated macrophages, then the tissue will become inflamed and the macrophages will be less able to defend the host from the invaders, which enables the disease to progress.  Once these insights are studied, polyamine transport inhibitors may provide a new therapy for IBD patients.