University of Dundee

Professor Pauline Schaap FRSE

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

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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
Schaap, P. (2011). Evolutionary crossroads in Developmental Biology: Dictyostelium discoideum.  Development 138, 387-396. 
doi/10.1242/dev.048934
 
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

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.