Professor Pauline Schaap FRSE
Most protozoa survive environmental stress by encapsulating to form a cyst or spore. This process is medically important because cysts of pathogenic protists are resistant to immune clearance, antibiotics and biocides. In addition, cysts of bacterivorous protists such as Acanthamoeba castellani are exploited act as vectors for survival and airborne dispersal by bacterial pathogens, such as Legionella pneumoniae and MRSA. Due to the limited genetic tractability of encysting organisms, the mechanisms controlling encystation are largely unknown.
Dictyostelid social amoebas survive stress by building fruiting structures with encapsulated spores and stalk cells. Both cell types mature in response to cAMP activation of PKA. We showed earlier that this process is evolutionary derived from encystation in solitary amoebas, which we found to also require cAMP acting on PKA. The encysting Dictyostelid Polysphondylium pallidum is uniquely suitable for both reverse and forward genetic approaches, which allowed us to identify several encystation genes that proved to be deeply conserved in protozoa. In current research we combine the power of genetics with proteomic approaches to identify all genes that control encystation in P.pallidum.
We also seek to identify missing links in the pathways that regulate spore and stalk cell encapsulation in Dictyostelia. We recently found that Dictyostelia use c-di-GMP, an important prokaryote second messenger, as a secreted signal to induce stalk formation. c-di-GMP activates the adenylate cyclase ACA, which in turn activates PKA. ACA also produces the cAMP pulses that coordinate Dictyostelium aggregation and fruiting body formation, and is specifically expressed at the organizing tip. The interaction between c-di-GMP and ACA explained why the stalk is always formed from the tip.
We aim to establish how this and other PKA mediated pathways emerged from the ancestral encystation pathway as part of our overriding interest to understand how multicellular organisms evolved and acquired ever increasing levels of organisational complexity.
Signalling pathways that regulate encystation of solitary amoebas and multicellular development in Dictyostelium. Red text: Extracellular signals, blue text: intracellular signal proteins and small molecules; green text: enzymes that produce extracellular signals. Modified from: Schaap, 2016. Curr Opin Genet Dev. 39:29-34.
ÖTwo lectures in the 3rd Developmental Biology course.
Supervision of special study components for 1st year medical students
Supervision of a 4th year honours students and summer students.
Yamada Y, Cassidy A, Schaap P (2018) The transcription factor Spores Absent A is a PKA dependent inducer of Dictyostelium sporulation. Scientific Reports. 8:1-13.
Schaap P, Schilde C. (2018) Encystation: the most prevalent and underinvestigated differentiation pathway of eukaryotes. Microbiology. 164:727-739.
Kawabe Y, Morio T, Tanaka Y, Schaap, P. (2018). Glycogen synthase kinase 3 promotes multicellular development over unicellular encystation in encysting Dictyostelia. EvoDevo. 9(12).
Hillmann F, Forbes G, Novohradská S, Ferling I, Riege K, Groth M, Westerman M, Marz M, Spaller T, Winckler T, Schaap P, Glöckner G. (2018) Multiple roots of fruiting body formation in Amoebozoa. Genome Biology and Evolution. 10(2):591-606
Singh, R., Lawal, H.M., Schilde, C., Glöckner, G., Barton, G., Schaap, P. and Cole, C. (2017) Improved annotation with de novo transcroptome assembly in four social amoeba species. BMC Genomics. 18, 120.
Narita, T.B, Schaap, P. and Saito, T. (2017) Effects of deletion of the receptor CrlA on Dictyostelium aggregation and MPBD-mediated responses are strain dependent and not evident in strain Ax2. FEMS Microbiology Letters. 364.
Chen, Z.H., Singh, R., Cole, C., Lawal, H., Schilde, C., Febrer, M., Barton, G.J., and Schaap, P. (2017). Adenylate cyclase A acting on PKA mediates induction of stalk formation by c-di-GMP at the Dictyostelium organizer. Proc. Natl. Acad. Sci. USA, 114, 516-521.
Singh, R., Schilde, C. and Schaap, P. (2016) A core phylogeny of Dictyostelia inferred from genomes representative of the eight major and minor taxonomic divisions of the group. BMC Evolutionary Biology. 6, 251.
Schilde, C., Lawal, H.M., Noegel, A.A., Eichinger, L., Schaap, P. and Glockner, G. (2016) A set of genes conserved in sequence and expression traces back the establishment of multicellularity in social amoebae. BMC Genomics. 17, 871.
Gloeckner, G., Lawal, H.M., Felder, M., Singh, R., Guild, G., Weijer, C.J., and Schaap, P. (2016). The multicellularity genes of Dictyostelid social amoebas. Nature Communications| 7:12085.
Schaap, P. (2016) Evolution of developmental signalling in Dictyostelid social amoebas. Curr Opin Genet Dev. 39:29-34.
Chen, Z.H and Schaap, P. (2016). Secreted Cyclic Di-GMP induces stalk cell differentiation in the Eukaryote Dictyostelium discoideum. Journal of Bacteriology. 198, 27-31.
Sheikh, S., Gloeckner, G., Kuwayama, H., Schaap, P., Urushihara, H. and Baldauf, S.L. (2015). Root of Dictyostelia based on 213 Universal proteins. Molecular phylogenetics and evolution. 92, 53-62.
Kawabe, Y., Schilde, C., Du, Q., and Schaap, P. (2015). A conserved signalling pathway for amoebozoan encystation that was co-opted for multicellular development. Nature Scientific reports 5, 9644.
Schaap, P., Barrantes, I., Minx, P., Sasaki, N., Anderson, R. W., Benard, M., Biggar, K. K., Buchler, N. E., Bundschuh, R., Chen, X., et al. (2015). The Physarum polycephalum genome reveals extensive use of prokaryotic two-component and metazoan-type tyrosine kinase signaling. Genome Biol Evol. 8, 109-125.
Du, Q., Kawabe, Y., Schilde, C., Chen, Z.H. and Schaap, P. (2015). The Evolution of Aggregative Multicellularity nad Cell-Cell Communication in hte Dictyostelia. Journal of Molecular Biology. 427, 3722-3733. d.o.i 10.1016/j.jmb.2015.08.008
Together with our collaborators, we have provided the research community with the first molecular phylogeny of Dictyostelia, and with three finished genomes which, with the D.discoideum genome, represent the four major groups of the Dictyostelid phylogeny. This information allows investigators to identify core components of any biological process studied in Dictyostelia and to retrace the evolutionary history of the process under study. This raises the characterization of a process from not only knowing its component parts, to also understanding why the process is built up the way it is.
Dictyostelium discoideum is already widely used to study fundamental processes related to human disease, but our research has opened new opportunities to use dictyostelids as genetically tractable models for understanding protist-borne disease. Most unicellular protists, including many pathogens, form resilient cysts when exposed to stress. By sequencing its genome and developing tools for molecular genetic analysis of the encysting dictyostelid Polysphondylium pallidum, we have established a genetically tractable model for studying amoebozoan encystation.