Defensins as Agents of Mucosal Innate Immunity

Mentor: Charles L. Bevins, MD PhD
Feb. 14, 2006
Description:
The mucosal surfaces of our body continually encounter microbes that have a capacity to cause infectious disease. Why don't we more commonly see infections caused by the bacteria and fungi that inhabit these surfaces? Many new studies have indicated that innate immunity provides a constant, vigilant, highly effective protection to keep our mucosal surfaces free from infectious and inflammatory disease, thus allowing these surfaces to carry out normal physiology. Our group has focused on one key component of mucosal innate immunity: defensin peptides.

Medical students with experience in working in a research laboratory will be offered a short term (6-10 week) semi-independent project for study. In some cases these projects can be extended into longer-term studies. The projects will take into account the previous experience of the student, but will likely include molecular biology or peptide chemistry. The student will obtain guidance and instruction with the specific techniques and methods, but it is expected that the student will have the motivation to follow through with the project.

Duration: Initially 6-10 weeks (may be extended)

References for the medical students to read to determine if they might be interested in the project:
1. Wehkamp, J, Salzman, NH, Porter, E, Weichenthal, M, Petras, RE, Shen, B, Schaeffeler, E, Schwab, M, Linzmeier, R, Feathers, RW, Chu, H, Lima, J, H., Fellermann, K, Ganz, T, Stange, EF, and Bevins, CL, Decreased Paneth cell defensins and antimicrobial activity in ileal Crohn's disease. Proc. Natl. Acad. Sci. 102:18129-18134, 2005.
2. Salzman, N., Ghosh, D., Huttner, K.M. Paterson, Y. and Bevins, C.L. Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature 422: 522-526, 2003.
3. Ghosh, D., Porter, E.M., Shen, B., Lee, S.K., Wilk, D.J., Crabb, J.W., Drazba, J., Yadav, S.Y., Ganz, T. and Bevins, C.L. Paneth cell trypsin is the processing enzyme for human defensin-5. Nat. Immunol. 3:583-590, 2002.
4. Bevins, C. L.: Paneth cell defensins in intestinal host defense. Am J. Physiol. 289: G173-176, 2005. (review)