Dr. Carmen Faso
Mechanisms of unconventional protein secretion
In our group, we study mechanisms of unconventional protein secretion in two intestinal parasitic protists called Giardia lamblia and Entamoeba histolytica.
We aim to employ a range of methods to determine the composition, phylogenetic history and structural identity of molecular machinery involved in the secretion of parasitic virulence factors. These molecules cause damage to the parasitized host and are often secreted unconventionally using mechanisms that are currently unknown.
Communication is intrinsic to life. Molecular exchange is one form of communication employed throughout all forms of life, including eukaryotic unicellular parasites. These organisms depend entirely on their hosts for survival, feeding off of host-acquired nutrients and often reproducing within them.
Giardia lamblia and Entamoeba histolytica are two such parasitic species causing giardiasis and entamoebiasis, respectively. These parasites colonize the intestinal tract of practically all vertebrates and in humans, they mainly cause diarrheal disease but may also lead to more permanent tissue and organ damage. Combined, G. lamblia and E. histolytica are responsible for over 300 million cases of diarrheal disease worldwide.
It has been known for several years that Giardia and Entamoeba establish infection by releasing specific proteins called virulence factors that help these parasites colonize hosts while modulating the host’s ability to counteract the invasion through the immune system.
Although several secreted parasite proteins have been identified, the mechanisms that regulate this important phenomenon are still unknown. For this reason, our lab aims to determine the identity, composition and distribution of the molecular machines that mediate transport of virulence factors from the parasite cell to the host’s environment. Unravelling the nature of these machines may provide novel therapeutic targets while shedding light on unconventional strategies for molecular communication at the host-parasite interface.
Research in our laboratory is generously supported by the Swiss National Science Foundation PRIMA granting scheme.
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Cernikova, Lenka; Faso, Carmen; Hehl, Adrian B. (2020). Phosphoinositide-binding proteins mark, shape and functionally modulate highly-diverged endocytic compartments in the parasitic protist Giardia lamblia. PLoS pathogens, 16(2), e1008317. Public Library of Science 10.1371/journal.ppat.1008317
Cernikova, Lenka; Faso, Carmen; Hehl, Adrian B. (2019). Roles of Phosphoinositides and Their binding Proteins in Parasitic Protozoa. Trends in parasitology, 35(12), pp. 996-1008. Elsevier Current Trends 10.1016/j.pt.2019.08.008
Faso, Carmen; Hehl, Adrian B. (2019). A cytonaut's guide to protein trafficking in Giardia lamblia. Advances in Parasitology, 106, pp. 105-127. Elsevier 10.1016/bs.apar.2019.08.001
Rout, Samuel; Zumthor, Jon Paulin; Schraner, Elisabeth M; Faso, Carmen; Hehl, Adrian B (2016). An Interactome-Centered Protein Discovery Approach Reveals Novel Components Involved in Mitosome Function and Homeostasis in Giardia lamblia. PLoS pathogens, 12(12), e1006036. Public Library of Science 10.1371/journal.ppat.1006036
Zumthor, Jon Paulin; Cernikova, Lenka; Rout, Samuel; Kaech, Andres; Faso, Carmen; Hehl, Adrian B (2016). Static Clathrin Assemblies at the Peripheral Vacuole-Plasma Membrane Interface of the Parasitic Protozoan Giardia lamblia. PLoS pathogens, 12(7), e1005756. Public Library of Science 10.1371/journal.ppat.1005756
Grabliauskaite, Kamile; Saponara, Enrica; Reding, Theresia; Bombardo, Marta; Seleznik, Gitta M.; Malagola, Ermanno; Zabel, Anja; Faso, Carmen; Sonda, Sabrina; Graf, Rolf (2016). Inactivation of TGFβ receptor II signalling in pancreatic epithelial cells promotes acinar cell proliferation, acinar-to-ductal metaplasia and fibrosis during pancreatitis. Journal of pathology, 238(3), pp. 434-445. Wiley 10.1002/path.4666
Ebneter, Jacqueline A.; Heusser, Sally D.; Schraner, Elisabeth M.; Hehl, Adrian B.; Faso, Carmen (2016). Cyst-Wall-Protein-1 is fundamental for Golgi-like organelle neogenesis and cyst-wall biosynthesis in Giardia lamblia. Nature communications, 7(13859), p. 13859. Nature Publishing Group 10.1038/ncomms13859
Wampfler, Petra B.; Faso, Carmen; Hehl, Adrian B. (2014). The Cre/loxP system in Giardia lamblia: genetic manipulations in a binucleate tetraploid protozoan. International journal for parasitology, 44(8), pp. 497-506. Elsevier 10.1016/j.ijpara.2014.03.008
Faso, Carmen; Konrad, Christian; Schraner, Elisabeth M.; Hehl, Adrian B. (2013). Export of cyst wall material and Golgi organelle neogenesis in Giardia lamblia depend on endoplasmic reticulum exit sites. Cellular microbiology, 15(4), pp. 537-553. Blackwell 10.1111/cmi.12054
Faso, Carmen; Bischof, Sylvain; Hehl, Adrian B (2013). The proteome landscape of Giardia lamblia encystation. PLoS ONE, 8(12), e83207. Public Library of Science 10.1371/journal.pone.0083207
Conger, Renata; Chen, Yani; Fornaciari, Silvia; Faso, Carmen; Held, Michael A.; Renna, Luciana; Brandizzi, Federica (2011). Evidence for the involvement of the Arabidopsis SEC24A in male transmission. Journal of Experimental Botany, 62(14), pp. 4917-4926. Oxford University Press 10.1093/jxb/err174
Faso, Carmen; Hehl, Adrian B (2011). Membrane trafficking and organelle biogenesis in Giardia lamblia: use it or lose it. International journal for parasitology, 41(5), pp. 471-480. Elsevier 10.1016/j.ijpara.2010.12.014
Vanderschuren, Hervé; Heinzmann, Dominik; Faso, Carmen; Stupak, Martin; Arga, Kazim Yalçin; Hoerzer, Helen; Laizet, Yech’an; Leduchowska, Paulina; Silva, Nádia; Šimková, Klára (2010). A cross-sectional study of biotechnology awareness and teaching in European high schools. New biotechnology, 27(6), pp. 822-828. Elsevier 10.1016/j.nbt.2010.01.338
Faso, Carmen; Boulaflous, Aurelia; Brandizzi, Federica (2009). The plant Golgi apparatus: last 10 years of answered and open questions. FEBS letters, 583(23), pp. 3752-3757. Elsevier 10.1016/j.febslet.2009.09.046
Faso, Carmen; Chen, Ya-Ni; Tamura, Kentaro; Held, Michael; Zemelis, Starla; Marti, Lucia; Saravanan, RamuSubramanian; Hummel, Eric; Kung, Leslie; Miller, Elizabeth; Hawes, Chris; Brandizzi, Federica (2009). A missense mutation in the Arabidopsis COPII coat protein Sec24A induces the formation of clusters of the endoplasmic reticulum and Golgi apparatus. The Plant Cell, 21(11), pp. 3655-3671. American Society of Plant Biologists 10.1105/tpc.109.068262