Drosophila as a model host to study innate immunity
Co-workers: Marcus Glittenberg, Ilias Kounatidis, Magda Atilano, Lihui Wang, Rupal Mistry, Jack Dorling, Jiwon Park, Peter Burns, Sergio Filipe (sabbatical visitor)
The fruit fly Drosophila melanogaster provides a major model system for examining many different biological problems. Our research makes use of Drosophila for investigations into innate immunity the first line host defence conserved in all metazoans. Research in our laboratory is developing along three major lines:
1. Innate immunity is dependent on germ-line coded receptors that recognise conserved pathogen-associated molecules that do not exist in the host. We are investigating the question of how a relatively small number of such receptors are able to sense the vast variability of pathogens and how host recognition changes when the microbial cell wall is altered.
2. Despite the extensive conservation between Drosophila and mammalian innate immunity it is still an open question whether Drosophila (as an ethically neutral model) can be used to study human pathogens. We are using Candida albicans and Candida glabrata to adress this question by establishing infection models and conducting genetic screens focusing on host susceptibility to infection as well as pathogen attributes that cause disease.
3. We are developing Drosophila as a model for studying infection by gut-dwelling trypanosomatid parasites that naturally infect fruitflies. Making use of the sophisticated tool-box available for Drosophila will help "unlock" more difficult, medically important insects vectors of parasitic disease like sandflies or tsetse flies.
Hepburn L, Prajsnar TK, Klapholz C, Moreno P, Loynes CA, Ogryzko NV, Brown K, Schiebler M, Hegyi K, Antrobus R, Hammond KL, Connolly J, Ochoa B, Bryant C, Otto M, Surewaard B, Seneviratne SL, Grogono DM, Cachat J, Ny T, Kaser A, Torok, ME, Peacock SJ, Holden M, Blundell T, Wang L, Ligoxygakis P, Minichello L, Foster SJ, Renshaw SA, Floto RA (2014). Innate Immunity. A Spaetzle-like role for nerve growth factor beta in vertebrate immunity to Staphylococcus aureus. Science 346 (6209): 641-646 doi:10.1126/science.1258705
Atilano ML, Pereira PM, Vaz F, Catalao MJ, Reed P, Grilo IR, Sobral RG, Ligoxygakis P, Pinho MG, Filipe SR (2014). Bacterial autolysins trim cell surface peptidoglycan to prevent detection by the Drosophila immune system. Elife 3, e02277 doi:10.7554/eLife.02277.
Fernando MD, Kounatidis I and Ligoxygakis P (2014). Loss of Trabid, a new negative regulator of the Drosophila immune-deficiancy pathway at the level of TAK1, reduces life span. PLoS Genet 10(2):e1004117doi: 10.1371/journalpgen.1004117.
Wang L, Kounatidis I and Ligoxygakis P (2014). Drosophila as a model to study the role of blood cells in inflammation, innate immunity and cancer. Front Cell Infect Microbiol 3, 113 doi:10.3389/fcimb.2013.00113. More Publications...
GFP expression controlled by the promoter of the antimicrobial peptide (AMP) gene drosomycin. In non-infected flies (top left panel) GFP is expressed only in barrier epithelia whereas following infection, systemic expression of GFP can be observed. Top right panel shows the same phenomenon in larvae. The fat body (the insect equivalent of the mammalian liver) is the major site of synthesis and secretion of AMPs (bottom two panels)