University of Dundee

Professor Pauline Schaap FRSE FRSB

Experimental and evolutionary reconstruction of developmental signalling pathways
Position: 
Professor of Developmental Signalling
Address: 
School of Life Sciences, University of Dundee, Dundee
Full Telephone: 
+44 (0) 1382 388078, int ext 88078
Email: 

Research

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.

 

 

 

 

Teaching

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.

Publications

Kabbara, S., Hérivaux, A., Dugé de Bernonville, T., Courdavault, V.,Clastre, M., Gastebois, A., Osman, M., Hamze, M., Cock, J. M., Schaap, P., Papon, N. (2019) Diversity and Evolution of Sensor Histidine Kinases in Eukaryotes. Genome Biology and Evolution,  Volume 11, Issue 1 pg86-108
doi/10.1093/gbe/evy213 Read Article
 
Schilde, C., Lawal, H M., Kin, K., Shibano-Hayakawa, I., Inouye, K., Schaap, P. (2019) A well supported multi gene phylogeny of 52 dictyostelia. Molecular Phylogenetics and Evolution Volume 134, May 2019, Pages 66-73. doi.org/10.1016/j.ympev.2019.01.017 PMID 30711536 Read Article
 
Yamada, Y., Schaap, P. (2019) Cyclic AMP induction of Dictyostelium prespore gene expression requires autophagy. Developmental Biology Volume 449, Issue 1 doi/10.1016/j.ydbio.2019.04.017 PMID 31051160 Read Article
 
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.  doi/10.1093/gbe/evy011 PMCID 5804921
PMID 29378020 Read Article
 
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).  doi.org/10.1186/s13227-018-0101-6  Read Article
 
Kin, K., Forbes, G., Cassidy, A., Schaap, P. (2018) Cell-type specific RNA-Seq reveals novel roles and regulatory programs for terminally differentiated Dictyostelium cells.  BMC Genomics201819:764. doi/10.1186/s12864-018-5146-3 PMCID 6198379 PMID 30348074 Read Article
 
Schaap P, Schilde C. (2018) Encystation: the most prevalent and underinvestigated differentiation pathway of eukaryotes.  Microbiology. 164:727-739.  doi/10.1099/mic.0.000653 PMID 29620506 Read Article
 
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.  doi/10.1038/s41598-018-24915-w PMID 29704004 Read Article
 
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. doi/10.1186/s12864-017-3505-0 PMCID 5282741 PMID 28143409 Read Article
 
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. 
doi.org/10.1093/femsle/fnx022 Read Article
 
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.  doi/10.1073/pnas.1608393114
PMCID 5255622 PMID 28057864 Read Article
 
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.  doi/10.1186/s12862-016-0825-7 PMCID 5114724 PMID 27855631 Read Article
 
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. doi.org/10.1186/s12864-016-3223-z Read Article
 
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.  doi/10.1038/ncomms12085 Read Article
 
Schaap, P. (2016) Evolution of developmental signalling in Dictyostelid social amoebas. Curr Opin Genet Dev. 39:29-34.  doi/10.1016/j.gde.2016.05.014 PMCID 5113120 PMID 27318097 Read Article
 
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.  doi/10.1128/JB.00321-15 Read Article
 
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
 
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. doi/10.1016/j.ympev.2015.05.017  PMID 26048704 Read Article
 
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.  doi.org/10.1038/srep09644 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
 
Du, Q., Kawabe, Y., Schilde, C., Chen, Z.H. and Schaap, P.(2015). The Evolution of Aggregative Multicellularity and Cell-Cell Communication in the Dictyostelia.  Journal of Molecular Biology. 427, 3722-3733. doi/10.1016/j.jmb.2015.08.008. PMCID 5055082 PMID 26284972 Read Article
 
Chen, Z.H., Rafellberg, S., Losi, A., Schaap, P. and Gartner, W. (2014) A cyanobacterial light activated adenyl cyclase partially restores development of a Dictyostelium discoideum, adenylyl cyclase a null mutanat.  Journal of biotechnology.  191, 246-249 doi/10.1016/j.jbiotec.2014.08.008. 
PMCID 4409636 PMID 25128613 Read Article
 
Du, Q and Schaap, P (2014) The Social amoeba Polysphondylium pallidum loses encystation and sporulation, but can still erect fruiting bodies in the absence of cellulose.  Protist. 165, 569-579. doi/10.1016/j.protis.2014.07.003 PMCID 4210663 PMID 25113829 Read Article
 
Du, Q., Schilde, C., Birgersson, E., Chen, Z. H., McElroy, S., and Schaap, P. (2014). The cyclic AMP phosphodiesterase RegA critically regulates encystation in social and pathogenic amoebas. Cell Signal. 26, 453-459. doi/10.1016/j.cellsig.2013.10.008 PMCID 3906536 PMID 24184654 Read Article
 
Narita, T.B., Chen, Z.H., Schaap, P., and Saito, T. (2014) The hybrid type ployketide synthase SteelyA is required for cAPM signalling in early Dictyostelium development.  PloS One. 9, e106634.  doi.org/10.1371/journal.pone.0106634 PMCID 4164351 PMID 25222736 Read Article
 
Schilde, C., Skiba, A., and Schaap, P. (2014). Evolutionary reconstruction of pattern formation in 98 Dictyostelium species reveals that cell-type specialization by lateral inhibition is a derived trait. EvoDevo 5, 34.  doi.org/10.1186/2041-9139-5-34 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
 
Romeralo, M., Skiba, A., Gonzalez-Voyer, A., Schilde, C., Lawal, H., Kedziora, S., Cavender, J. C., Glockner, G., Urushihara, H., and Schaap, P. (2013). Analysis of phenotypic evolution in Dictyostelia highlights developmental plasticity as a likely consequence of colonial multicellularity. Proc R. Soc. B. 280, 20130976. doi/10.1098/rspb.2013.0976 PMCID 3712420 PMID: 23782883 Read Article
 
Clarke, M., Lohan, A. J., Liu, B., Lagkouvardos, I., Roy, S., Zafar, N., Bertelli, C., Schilde, C.,Schaap, P., et al (2013) Genome of Acanthamoeba castellanii highlights extensive lateral gene transfer and early evolution of tyrosine kinase signaling.  Genome Biology201314:R11. doi/10.1186/gb-2013-14-2-r11 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
 
Chen, Z-H and Schaap, P. (2012) The prokaryote messenger c-di-GMP triggers stalk cell differentiation in Dictyostelium. Nature 488, 680-683.  doi/10.1038/nature11313 PMCID 3939355 PMID 22864416 Read Article
 
Kawabe, Y., Weening, K.E., Marquay-Markiewicz, J., and Schaap, P. (2012). Evolution of self-organisation in Dictyostelia by adaptation of a non-selective phosphodiesterase and a matrix component for regulated cAMP degradation. Development 139, 1336-1345.  doi/10.1242/dev.077099
PMCID 3294436 PMID 22357931 Read Article
 
Heidel, A., Lawal, H., Felder, M., Schilde, C., Helps, N., Tunggal, B., Rivero, F., John, U., Schleicher, M., Eichinger, L., Platzer, M., Noegel, A., Schaap, P* and Glockner, G*. (2011). Phylogeny-wide analysis of social amoeba genomes highlights ancient origins for complex intercellular communication. Genome research, 21, 1882-1891.* joint corresponding authors.  doi/10.1101/gr.121137.111 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. (2011). Evolutionary crossroads in Developmental Biology: Dictyostelium discoideum.  Development 138, 387-396.  doi/10.1242/dev.048934 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
 
Chen, Z., Schilde, C., Schaap, P. (2010) Functional dissection of Adenylate Cyclase R, an inducer of spore encapsulation.  The Journal of Biological Chemistry Vol. 285, NO. 53, pp. 41724 –41731
doi/10.1074/jbc.M110.156380 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
 
Kawabe, Y., Morio, T., James, J. L., Prescott, A. R., Tanaka, Y. and Schaap, P. (2009) Activated cAMP receptors turn encystation into sporulation. Proc. Nat. Acad. Sci. USA, 106, 7089-7094.  doi/10.1073/pnas.0901617106 PMCID 2678454 PMID 19369200 Read Article
 
Kawabe, Y., Alvarez-Curto, E., Ritchie, A. V., Schaap, P. (2009) The evolution of morphogenetic signalling in social amoebae. Evolutionary Biology pp 91-107
doi/10.1007/978-3-642-00952-5_5
 
Kawabe, Y., Morio, T., Tanaka, Y and Schaap, P. (2008) Activated cAMP receptors turn encystation into sporulation.  PNAS,106(17) 7089 –7094. doi/10.1073/pnas.0901617106 PMCID 2678454 PMID 19369200 Read Article
 
Ritchie, A. V., van Es, S., Fouquet, C., Schaap, P (2008) From drought sensing to developmental control: evolution of cyclic AMP signaling in social amoebas. Molecular Biology and Evolution, Volume 25(10) Pages 2109–2118. doi/10.1093/molbev/msn156 PMCID 2535757 PMID 18640994 

Impact

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.