This Project focuses on the defining molecules that are necessary for phagocytosis. Phagocytosis is primary a specialized function of myeloid cells. Phagocytosis of microorganisms plays a key role in host defense. Engulfment of microorganisms and senescent cells by phagocytic cells is a complex multistep process. Hitherto, identification of molecules that play a key role in phagocytosis has been largely confined to in vitro mammalian systems. In this project, we propose to combine the powerful tools of Drosophila genetics that will allow us to study phagocytosis in vivo with in vitro cellular and biochemical studies that make use of Drosophila macrophage cell lines. Furthermore, we aim to apply the lessons learnt in Drosophila to mammalian systems. We plan to use both loss-of-function mutant analysis, and misexpression in vivo to explore the role of candidate molecules in this process. In addition, we propose three major genetic screens to detect other molecules that play a role in phagocytosis. We believe that the approaches outlined in this Project 1 of the Program Project Grant will provide new insights into the regulation of phagocytosis and, as such, will have direct applicability to gaining greater insights into microbial host interactions.

Project Start
1999-09-01
Project End
2000-08-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Gendrin, Mathilde; Turlure, Fanny; Rodgers, Faye H et al. (2017) The Peptidoglycan Recognition Proteins PGRPLA and PGRPLB Regulate Anopheles Immunity to Bacteria and Affect Infection by Plasmodium. J Innate Immun 9:333-342
Lombardo, Fabrizio; Christophides, George K (2016) Novel factors of Anopheles gambiae haemocyte immune response to Plasmodium berghei infection. Parasit Vectors 9:78
Lombardo, Fabrizio; Ghani, Yasmeen; Kafatos, Fotis C et al. (2013) Comprehensive genetic dissection of the hemocyte immune response in the malaria mosquito Anopheles gambiae. PLoS Pathog 9:e1003145
Cezairliyan, Brent; Vinayavekhin, Nawaporn; Grenfell-Lee, Daniel et al. (2013) Identification of Pseudomonas aeruginosa phenazines that kill Caenorhabditis elegans. PLoS Pathog 9:e1003101
Feinbaum, Rhonda L; Urbach, Jonathan M; Liberati, Nicole T et al. (2012) Genome-wide identification of Pseudomonas aeruginosa virulence-related genes using a Caenorhabditis elegans infection model. PLoS Pathog 8:e1002813
Chung, Yoon-Suk Alexander; Kocks, Christine (2012) Phagocytosis of bacterial pathogens. Fly (Austin) 6:21-5
Whiteman, Noah K; Gloss, Andrew D; Sackton, Timothy B et al. (2012) Genes involved in the evolution of herbivory by a leaf-mining, Drosophilid fly. Genome Biol Evol 4:900-16
Pukkila-Worley, Read; Ausubel, Frederick M (2012) Immune defense mechanisms in the Caenorhabditis elegans intestinal epithelium. Curr Opin Immunol 24:3-9
Chung, Yoon-Suk Alexander; Kocks, Christine (2011) Recognition of pathogenic microbes by the Drosophila phagocytic pattern recognition receptor Eater. J Biol Chem 286:26524-32
Limmer, Stefanie; Haller, Samantha; Drenkard, Eliana et al. (2011) Pseudomonas aeruginosa RhlR is required to neutralize the cellular immune response in a Drosophila melanogaster oral infection model. Proc Natl Acad Sci U S A 108:17378-83

Showing the most recent 10 out of 88 publications