Professor Pauline Schaap FRSE FRSB
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.
Two 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.
Schaap, P., Barrantes, I., Minx, P., Sasaki, N., et al. (2016) The Physarum polycephalum Genome Reveals Extensive Use of Prokaryotic Two-Component and Metazoan-Type Tyrosine Kinase Signaling. Genome Biology and Evolution Volume 8 Issue 1. doi/10.1093/gbe/evv237 PMCID 4758236 PMID 26615215 Read Article
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. doi/10.1093/gbe/evv237 PMCID 4758236 PMID 26615215 Read Article
Schaap, P. (2013) Cyclic di-nucleotide signaling enters the eukaryote domain. IUBMB Life. 2013 Nov;65(11):897-903. doi/10.1002/iub.1212 PMCID 3937738 PMID 24136904 Read Article
Schilde, C., Schaap, P. (2013) The Amoebozoa. Dictyostelium discoideum Protocols pp 1-15. doi/10.1007/978-1-62703-302-2_1 PMCID 4037983 PMID 23494299 Read Article
Schaap, P. (2011) Evolution of developmental cyclic adenosine monophosphate signaling in the Dictyostelia from an amoebozoan stress response. Development, Growth & Differentiation Volume53, Issue 4. doi/10.1111/j.1440-169X.2011.01263.x PMCID 3909795 PMID 21585352 Read Article
Schaap, P., et al. (2011) Comparative genomics of the social amoebae Dictyostelium discoideum and Dictyostelium purpureum. Genome Biology201112:R20. doi/10.1186/gb-2011-12-2-r20 PMCID 3188802 PMID 21356102 Read Article
Schapp, P. (2010) Evolutionary crossroads in Developmental Biology: Dictyostelium discoideum. Development. 2011 Feb;138(3):387-96. doi/10.1242/dev.048934 PMCID 3014629 PMID 21205784 Read Article
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.